vitamin-k-semiquinone-radical and Atrial-Fibrillation

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Hypertension, Pulmonary; Vitamin K

In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT).. A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method.. Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]).. In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Stroke; Treatment Outcome; Vitamin K

Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when it comes to anticoagulation due to its several limitations. Direct oral anticoagulants (DOACs) have entered the market as a noninferior and safer option in comparison with vitamin K antagonists, as their respective phase III clinical trials proved. The aim of this article was to update and summarize data on their clinical pharmacology and to review real-world data to know their comparative effectiveness and safety. We performed a systematic review using PubMed, Google Scholar, Embase, and Web of Science as search engines. Regarding pharmacodynamics, there were no substantial changes reported from their original profile. There were many advances in the knowledge about clinical pharmacokinetics of DOACs that have had a direct impact on their clinical use, mainly related to drug-drug interactions. In a real-world setting, DOACs have shown to be noninferior in preventing thromboembolic events compared to vitamin K antagonists. In regards to safety, DOACs have shown a lower bleeding risk relative to warfarin. Comparison between DOACs has demonstrated rivaroxaban to have the highest bleeding risk. Overall, the evidence gathered showed few changes from the original data presented in phase III clinical trials, concluding that their real-world use coincides greatly with them.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pharmacology, Clinical; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

Thromboembolic events in myeloproliferative neoplasms (MPNs) are one of the most important causes of mortality and morbidity, in which vitamin K antagonists (VKAs) have been used mostly. Recently, direct oral anticoagulants (DOACs) are used in venous thromboembolism (VTE) and cancer-associated thrombosis (CAT). With the adoption of data from CAT and VTE, the usage of DOACs in MPNs is increasing.. In this paper, we performed a systematic review to the current literature regarding the usage of DOACs in MPNs. Eleven studies involving 944 patients were included. The reasons for initiating DOACs were secondary prophylaxis for thrombosis (arterial or venous) and atrial fibrillation (AF) in 562 and 382 patients, respectively. A total of 84 (8.9%) recurrent thrombotic (arterial or venous) events recorded. Forty-six (8.1%) events occurred in the thrombosis group (arterial or venous) and 38 (9.9%) events occurred in patients with AF.. Ease of management and patient comfort should be regarded as benefits of DOACs compared to VKAs. However, it would be appropriate to bring an individualized approach until we obtain high-quality data with prospectively designed studies involving more patients and longer follow-up time concerning the use of DOACs in patients with MPNs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Myeloproliferative Disorders; Neoplasms; Thrombosis; Venous Thromboembolism; Vitamin K

The efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for the treatment of patients with left-sided bioprosthetic heart valves (BHV) and atrial fibrillation (AF) remain controversial. This study aims to perform a meta-analysis to evaluate the efficacy and safety of DOACs versus VKAs in this region.. We retrieved all relevant randomized controlled studies and observational cohort studies, which critically assessed the efficacy and safety of DOACs versus VKAs among patients with left-sided BHV and AF in databases of PubMed, Cochrane, ISI Web of Sciences, and Embase. The efficacy outcomes of this meta-analysis were stroke events and all-cause death when the safety outcomes included major and any bleeding.. The analysis integrated 13 studies while enrolling 27,793 patients with AF and left-sided BHV. DOACs reduced the rate of stroke by 33% compared with VKAs (risk ratio [RR] 0.67; 95% CI 0.50-0.91), with no increased incidence of all-cause death (RR 0.96; 95% CI 0.82-1.12). For safety outcomes, major bleeding was reduced by 28% using DOACs rather than VKAs (RR 0.72; 95% CI 0.52-0.99), while there was no difference in the events of any bleeding (RR 0.84; 95% CI 0.68-1.03). In addition, in patients younger than 75 years old, the stroke rate was reduced by 45% in the population using DOACs (RR 0.55; 95% CI 0.37-0.84).. Our meta-analysis demonstrated that in patients with AF and BHV, compared with VKAs, using DOACs was associated with reduced stroke and major bleeding events without an increase of all-cause mortality and any bleeding. In the population younger than 75 years old, DOAC might be more effective in preventing cardiogenic stroke.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Heart Valves; Hemorrhage; Humans; Stroke; Vitamin K

A systematic evaluation focused on efficacy and safety for electrical cardioversion of atrial fibrillation (AF) among different Direct Oral Anticoagulants (DOACs) has not been previously performed. In this setting, we conducted a meta-analysis of studies evaluating DOACs vs vitamin K antagonists (VKA) as common comparator.. We searched Cochrane Library, Pubmed, Web Of Science and Scopus databases for all English-only articles concerning studies that have estimated the effect of DOACs and VKA on stroke, transient ischemic attack or systemic embolism (SSE) and major bleeding (MB) events in AF patients undergoing electrical cardioversion. We selected 22 articles comprising 66 cohorts and 24,322 procedures (12,612 with VKA).. During follow-up (studies' median 42 days), 135 SSE (52 DOACs and 83 VKA) and 165 MB (60 DOACs and 105 VKA) were recorded. The overall pooled effects, DOACs vs VKA, was estimated by an univariate Odds Ratio of 0.92 (0.63-1.33; p = 0.645) for SSE and 0.58 (0.41-0.82; p = 0.002) for MB; at bivariate evaluation, adjusting for study type, were respectively 0.94 (0.55-1.63; p = 0.834) and 0.63 (0.43-0.92, p = 0.016). Each single DOAC showed similar and non statistically different results in outcome occurrence compared to VKA as well as when Apixaban, Dabigatran, Edoxaban and Rivaroxaban were indirectly compared to each other.. In patients undergoing electrical cardioversion, compared to VKA, DOACs have similar thromboembolic protection with lower major bleeding incidence. Single molecule does not show difference in event rate compared to each other. Our findings, provide useful information about safety and efficacy profile of DOACs and VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Vitamin K

To address the following question: Are vitamin K antagonists (VKA) obsolete as stroke prevention therapy for patients with atrial fibrillation (AF) and thromboembolic risk factors?. A patient-level meta-analysis of the pivotal phase III randomized trials confirmed the favorable treatment effect of direct oral anticoagulants (DOAC) over VKA in multiple key patient subgroups. Among patients with AF and rheumatic heart disease (85% of whom had mitral stenosis), a randomized trial showed that rivaroxaban was not superior to VKA for stroke prevention. Caution should be exercised when prescribing DOAC for AF-related stroke prevention for patients with elevated body mass indices or history of bariatric surgery, patients with bioprosthetic heart valves, and those who require treatment with drugs that interact with cytochrome P450 and P-glycoprotein. Drug costs associated with DOAC remain considerably higher than VKA, by up to 30-fold. Direct oral anticoagulants are preferable over VKA in the large majority of eligible patients with AF and thromboembolic risk factors. The use of DOAC should be avoided for patients with mechanical heart valves or moderate/severe rheumatic mitral stenosis. Vitamin K antagonist is a reasonable option for patients who are under-represented in randomized trials, when there are significant drug-drug interactions or when patients cannot afford DOAC agents due to their higher costs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Mitral Valve Stenosis; Stroke; Thromboembolism; Vitamin K

Atrial fibrillation (AF) frequently complicates hypertrophic cardiomyopathy (HCM), and anticoagulation significantly decreases the risk of stroke in this population. To date, no randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). The present study aimed to systematically compare the two anticoagulation strategies in terms of effectiveness and safety.. We performed a systematic literature search and meta-analysis in the PubMed, MEDLINE, and EMBASE databases for studies reporting all-cause mortality, major bleeding, or thromboembolic events (TEs). Since no RCTs were available, we included observational studies only. The overall hazard ratio (HR) and 95% confidence interval (CI) for each analyzed parameter were pooled using a random-effects model.. Five observational studies including 6919 patients were eligible for inclusion. Compared with VKAs, DOACs were associated with statistically significant lower rates of all-cause mortality (HR 0.64, 95% CI 0.35-0.54; p < 0.00001), comparable major bleeding events (HR 0.64, 95% CI 0.40-1.03; p = 0.07), and TEs (HR 0.94, 95% CI 0.73-1.22; p = 0.65).. Compared with VKAs, a DOAC-based strategy might represent an effective and safe strategy regarding all-cause mortality, major/life-threatening bleeding complications, and TEs in HCM patients with concomitant AF. However, further prospective studies are necessary to reinforce a DOAC-based anticoagulation strategy in this population.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Hemorrhage; Humans; Stroke; Thromboembolism; Vitamin K

Randomized controlled trials (RCTs) are subject to bias if they lack methodological quality. Furthermore, optimal and transparent reporting of RCT findings aids their critical appraisal and interpretation. This study aimed to comprehensively evaluate the report quality of RCTs of non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF) and to analyze the factors influencing the quality.. By searching PubMed, Embase, Web of Science, and Cochrane Library databases RCTs published from inception to 2022 evaluating the efficacy of NOACs on AF were collected. By using the 2010 Consolidated Standards for Reporting Tests (CONSORT) statement, the overall quality of each report was assessed.. Sixty-two RCTs were retrieved in this study. The median of overall quality score in 2010 was 14 (range: 8.5-20). The extent of compliance with the Consolidated Standards of Reporting Trials reporting guideline differed substantially across items: 9 items were reported adequately (more than 90%), and 3 were reported adequately in less than 10% of trials. Multivariate linear regression analysis showed that the higher reporting scores were associated with higher journal impact factor (P = 0.01), international collaboration (P < 0.01), and Sources of trial funding (P = 0.02).. Although a large number of randomized controlled trials of NOACs for the treatment of AF were published after the CONSORT statement in 2010, the overall quality is still not satisfactory, thus weakening their potential utility and may mislead clinical decisions. This survey provides the first hint for researchers conducting trials of NOACs for AF to improve the quality of reports and to actively apply the CONSORT statement.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Randomized Controlled Trials as Topic; Vitamin K

Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF).. A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.. Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7).. Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Rivaroxaban; Stroke; Vitamin K

Atrial fibrillation (AF) patients are more susceptible to dementia, but the results about the effect of oral anticoagulants (OACs) on the risk of dementia are not consistent. We hypothesize that OAC is associated with a reduced risk of dementia with AF and that nonvitamin K antagonist oral anticoagulants (NOAC) are superior to vitamin K antagonists (VKA). Four databases were systematically searched until July 1, 2022. Two reviewers independently selected literature, evaluated quality, and extracted data. Data were examined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Fourteen research studies involving 910 patients were enrolled. The findings indicated that OACs were associated with a decreased risk of dementia (pooled HR: 0.68, 95% CI: 0.55-0.82, I

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dementia; Humans; Incidence; Prospective Studies; Stroke; Vitamin K

Patients who underwent transcatheter aortic valve implantation (TAVI) with concomitant atrial fibrillation (AF) are at a higher risk for thromboembolic and bleeding events. The optimal antithrombotic strategy for patients with AF after TAVI remains unclear. We sought to determine the comparative efficacy and safety of direct oral anticoagulants (DOAC) versus oral vitamin K antagonists (VKAs) in these patients. Electronic databases such as PubMed, Cochrane, and Embase databases were searched till January 31, 2023, for relevant studies evaluating clinical outcomes of VKA versus DOAC in patients with AF after TAVI. Outcomes assessed were (1) all-cause mortality, (2) stroke, (3) major/life-threatening bleeding, and (4) any bleeding. Hazard ratios (HRs) were pooled in meta-analysis using random effect model. Nine studies (2 randomized and 7 observational) were included in systematic review, and 8 studies with 25,769 patients were eligible to be included in the meta-analysis. The mean age of the patients was 82.1 years, and 48.3% were male. Pooled analysis using random-effects model showed no statistically significant difference in all-cause mortality (HR 0.91, 95% confidence interval [CI] 0.76 to 1.10, p = 0.33), stroke (HR 0.96, 95% CI 0.80 to 1.16, p = 0.70), and major/life-threatening bleeding (HR 1.05, 95% CI 0.82 to 1.35, p = 0.70) in patients that received DOAC compared with oral VKA. Risk of any bleeding was lower in the DOAC group compared with oral VKA (HR 0.83, 95% CI 0.76 to 0.91, p = 0.0001). In patients with AF, DOACs appear to be a safe alternative oral anticoagulation strategy to oral VKA after TAVI. Further randomized studies are required to confirm the role of DOACs in those patients.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Randomized Controlled Trials as Topic; Stroke; Transcatheter Aortic Valve Replacement; Vitamin K

Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dementia; Fibrinolytic Agents; Humans; Stroke; Vitamin K

Although guidelines give preference to direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF), DOACs are not recommended in those with rheumatic heart disease or mechanical heart valves. The results of the INVICTUS trial (Investigation of Rheumatic AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies), which compared rivaroxaban with a VKA in patients with rheumatic heart disease-associated AF, and the PROACT Xa trial (A Trial to Determine if Participants with an On-X Aortic Valve Can be Maintained Safely on Apixaban), which compared apixaban with warfarin in patients with an On-X valve in the aortic position, support the use of VKAs for these indications. In this paper, we review the results of these trials, provide perspective on why VKAs were superior to DOACs, and discuss future directions for anticoagulation in these disorders.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Fibrinolytic Agents; Humans; Pyridones; Rheumatic Heart Disease; Rivaroxaban; Stroke; Vitamin K; Warfarin

Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC).. This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC.. A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3.. Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08).. DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Liver Cirrhosis; Prospective Studies; Stroke; Thromboembolism; Vitamin K

In the last decade, non-vitamin K antagonist oral anticoagulants (NOACs), a new generation of OACs, were introduced to prevent thromboembolism in patients with atrial fibrillation. Although vitamin K-dependent anticoagulants have long been used as OACs, their inherent disadvantage of considerable bleeding complications has limited their use. NOACs demonstrate similar or superior clinical outcomes to those of warfarin. Although strict dose reduction criteria are recommended for NOACs, low-dose NOACs are frequently utilized, especially in Asian patients. Low-dose NOACs have shown clinical outcomes similar to those of warfarin in randomized controlled trials (RCTs) and real-world studies. However, off-label low-dose NOACs have shown inconsistent results compared with standard-dose NOACs and warfarin. Therefore, strict dose reduction criteria for NOACs should be followed until RCTs confirm the issues associated with NOAC underdosing.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Patients; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran. Although vitamin K antagonists (VKAs) have been traditionally used to prevent thromboembolic events, DOACs have gained popularity because of their faster onset and offset of action and reduced need for monitoring. This study aimed to provide more data for anticoagulants in patients with atrial fibrillation with bioprosthetic heart valves by incorporating all available trials to date. A search was performed across 5 electronic databases to identify relevant studies. We analyzed the data using a pooled risk ratio for categorical outcomes and used the I

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Stroke; Thromboembolism; Vitamin K

The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remains uncertain. We conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation.. Medline and Embase were searched through March 2021 to identify randomized controlled trials (RCTs) and observational studies investigating the outcomes of DOAC therapy and VKA therapy in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism.. DOAC might decrease the risk of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared with VKA in patients with bioprosthetic valves and atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Observational Studies as Topic; Stroke; Vitamin K

We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF).. A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.. Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1).. Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Rivaroxaban; Stroke; Vitamin K

Patients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair.. We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding.. We included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02).. In patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.

Topics: Anticoagulants; Atrial Fibrillation; Bioprosthesis; Heart-Assist Devices; Humans; Vitamin K; Warfarin

To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs).. Systematic review and meta-analysis.. We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019.. Patients with AF.. The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I. A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I. Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP.. CRD 42019146610.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Fibrinolytic Agents; Humans; Stroke; Vitamin K

Patients with atrial fibrillation (AF) who take direct oral anticoagulants (DOACs) face the risk of intracranial hemorrhage (ICH), which can be serious and even life threatening, but the risk of ICH of anticoagulants is still controversial. In this meta-analysis, we compared the risk of ICH between vitamin K antagonists (VKAs) and DOACs. Furthermore, we also compared the risk of ICH in different DOACs. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials. The outcome was ICH, shown as the odds ratio (OR) with a 95% confidence interval (CI). DOACs were ranked by calculating the surface under the cumulative ranking curve (SUCRA). We included a total of 82,404 patients with AF. DOACs reduced the ICH risk by nearly half compared with VKAs (OR 0.47, 95% CI 0.40 to 0.54, p <0.001). VKAs were the least safe among all oral anticoagulants (SUCRA 1.7). Dabigatran 110 mg was the safest DOAC (SUCRA 87.3) for ICH risk, whereas rivaroxaban 20 mg was a relatively unsafe DOAC (SUCRA 27.5). Compared with rivaroxaban 20 mg, dabigatran 110 mg presented 53% (OR 0.47, 95% CI 0.27 to 0.82) lower relative risk for ICH. In conclusion, DOACs present less ICH risk than VKAs in patients with AF. For patients with AF who are at high risk of ICH, dabigatran 110 mg may be the safest choice among the DOACs.

Topics: Atrial Fibrillation; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Stroke; Vitamin K

The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use. Beyond rate and rhythm control considerations, stroke prophylaxis is critical to AF management, and the benefits of direct OACs, compared with warfarin, extend to older adults. Invasive procedures such as AF catheter ablation, pacemaker implantation/atrioventricular junction ablation, and left atrial appendage occlusion may be useful in appropriately selected cases. However, older adults have generally been under-represented in clinical trials.

Topics: Accidental Falls; Aged; Alcohol Drinking; Anti-Arrhythmia Agents; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Cognitive Dysfunction; Coronary Artery Disease; Cost-Benefit Analysis; Decision Making, Shared; Dementia; Diabetes Mellitus; Dual Anti-Platelet Therapy; Exercise; Frailty; Heart Failure; Humans; Hypertension; Overweight; Polypharmacy; Primary Prevention; Risk Assessment; Secondary Prevention; Sleep Apnea, Obstructive; Stroke; Vitamin K; Weight Loss

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Vitamin K

Adverse effects of drugs are one of the objective criteria used for choosing the most appropriate anticoagulant. It is worrying that warfarin may be involved in the progression of systemic atherosclerosis, as more and more articles suggest. Warfarin has been widely used in the past and has greater efficacy compared to dabigatran in patients with mechanical heart valves; there is an antidote to it and it is cheap. Unfortunately, warfarin inhibits the synthesis and activity of Matrix-Gla-Protein, which is the major vitamin K-dependent inhibitor of arterial calcification - an active process associated with atherosclerosis, stimulated by inflammatory mechanisms. Vitamin K antagonizes the NF-κB signaling mechanism and contributes to the prevention of arterial calcifications. Warfarin given in experimental animal models of atherosclerosis contributed to the occurrence of an increased number of aortic calcifications. Warfarin treatment used in clinical trials was associated with the progressive increase of coronary atheroma calcification. Younger patients are more sensitive to warfarin-related arterial calcifications compared to older patients, due to warfarin-induced cellular senescence changes. Non-vitamin K antagonist direct oral anticoagulants do not interact with vitamin K. Edoxaban reduces the inflammatory process in the vascular walls and the proliferation of smooth vascular muscle cells, so it is involved in the prevention of vascular maladaptive remodeling process. Apixaban is able to stabilize the coronary atherosclerotic process. Randomized clinical trials are needed to evaluate the impact of warfarin on plaque stability and cardiovascular evolution of patients.

Topics: Administration, Oral; Animals; Anticoagulants; Atherosclerosis; Atrial Fibrillation; Humans; Stroke; Vitamin K; Warfarin

Left ventricular thrombi (LVTs) increase the risk of stroke, systemic embolism, and subsequent death. Current guidelines recommend vitamin K antagonists (VKAs) as first-line treatment for LVT. Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin for the treatment of LVT. However, the efficacy and safety of DOACs versus VKAs remain controversial. Thus, we conducted an updated meta-analysis of DOACs versus VKAs for LVT treatment. We systematically searched PubMed, Embase, ClinicalTrials, and Cochrane Library databases for relevant articles published before December 11, 2021. The relative risks (RRs) with 95% confidence intervals (CIs) were calculated for each study. The meta-analysis included 12 cohort studies and 3 randomized controlled trials with a total of 2334 patients. We found that DOACs had a lower risk of clinically significant bleeding than VKAs (RR = 0.6; 95% CI, 0.39 to 0.90; P = 0.01; I2 = 0%). There was no difference in LVT resolution (RR = 1.01; 95% CI, 0.93 to 1.09; P = 0.48; I2 = 0%), stroke and/or systematic embolic events (RR = 0.87; 95% CI, 0.11 to 1.55; P = 0.2; I2 = 30%), and all-cause mortality (RR = 0.9; 95% CI, 0.58 to 1.4; P = 0.65; I2 = 0%). Overall, DOACs are noninferior to warfarin in LVT treatment but have a lower risk of clinically significant bleeding. This suggests that DOACs might be better alternatives to warfarin for LVT treatment.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Thrombosis; Vitamin K; Warfarin

A Markov model was adapted to assess the real-world cost-effectiveness of rivaroxaban, dabigatran and apixaban. Each of these non-vitamin K antagonist oral anticoagulants was compared with vitamin K antagonist for stroke prevention in patients with non-valvular atrial fibrillation in Spain.. All inputs were derived from real-world studies: baseline patient characteristics, clinical event rates, as well as persistence rates for the vitamin K antagonist treatment option. A meta-analysis of real-world studies provided treatment effect and persistence data for rivaroxaban, dabigatran and apixaban, each compared with vitamin K antagonist therapy. The model considered 3-month cycles over a lifetime horizon. The model outcomes included different costs, quality-adjusted life years and life-years gained. Sensitivity analyses were performed to test the robustness of the model.. When compared with vitamin K antagonist, rivaroxaban incurred incremental costs of €77 and resulted in incremental quality-adjusted life years of 0.08. The incremental cost per quality-adjusted life year was €952. For the same comparison, the incremental cost per quality-adjusted life year for dabigatran was €4,612. Finally, compared with vitamin K antagonist, the incremental cost per quality-adjusted life year for apixaban was €32,015. The sensitivity analyses confirmed the robustness of the base case results. The probabilities to be cost-effective versus vitamin K antagonist were 94%, 86% and 35%, respectively, for rivaroxaban, dabigatran and apixaban, considering a willingness-to-pay threshold of €22,000 per quality-adjusted life year gained, based on a cost-effectiveness study of the Spanish National Health System.. These results suggest that rivaroxaban and dabigatran are cost-effective versus vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation, from the Spanish National Health System perspective.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Humans; Pyridones; Rivaroxaban; Spain; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Thrombosis; Vitamin K; Vitamins

The efficacy and safety of novel oral anticoagulants (NOACs) compared to the current guideline-recommended vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients undergoing transcatheter aortic valve replacement (TAVR) has not been well established. We pooled evidence from all available studies to assess the risks and benefits of this drug class.. We queried electronic databases (MEDLINE, Scopus, and Cochrane central) up until January 28th, 2022 for studies comparing NOACs to VKAs in AF patients undergoing TAVR. Results from studies were presented as risk ratios (RR) and pooled using a random-effects model. Subgroup analysis by study design and meta-regression analysis were performed to explore heterogeneity.. A total of 12 studies (3 RCTs and 9 observational) containing 12,203 patients (mean age 81.2 years; 50.5% men) were identified and included in the analysis. Pooled analysis revealed no significant difference between NOACs and VKAs in terms of stroke or systemic embolism (RR: 0.78; p = 0.18), major bleeding (RR: 0.84; p = 0.32), intracranial hemorrhage (RR 0.61; p = 0.06), all-cause mortality (RR: 0.69; p = 0.07), and myocardial infarction (RR: 1.60; p = 0.24) at a mean length of follow-up of 15.1 months. RCTs and observational studies did not significantly differ across outcomes on subgroup analysis. Meta-regression analysis found heterogeneity in all-cause mortality to be significantly explained by percentage of males (coefficient: 0.049, p = 0.007), mean age (coefficient: 0.221, p < 0.001), and CHA2DS2-VASc score (coefficient: -1.657, p < 0.001).. This meta-analysis suggests that outcomes with NOACs do not significantly differ compared to VKAs following TAVR in patients with AF.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Non-vitamin K oral anticoagulants (NOACs) are used for prevention of thromboembolic events, but their use in dialysis patients is debatable. This study investigated the available evidence for the use of NOACs in dialysis patients. Online databases were systematically searched for eligible studies including pharmacokinetic (PK) studies, cohort studies, and randomized control trials (RCTs) comparing NOAC with vitamin K antagonist (VKA) or no anticoagulant treatment. Newcastle Ottawa Scale and Cochrane Risk of bias tool were used for quality assessment. Twenty studies were identified (nine PK studies, two RCTs, and nine cohort studies). Most of the studies investigated apixaban or rivaroxaban. In dialysis patients, less accumulation was reported with apixaban and rivaroxaban compared to dabigatran and edoxaban. PK studies indicate that high dose apixaban or rivaroxaban should be avoided. The two RCTs (rivaroxaban/apixaban vs. VKA) were small and underpowered regarding stroke and bleeding outcomes. Most cohort studies found apixaban superior to VKA, whereas comparison of rivaroxaban with VKA yielded conflicting results. Cohort studies comparing apixaban high dose (5 mg) with low dose (2.5 mg) twice daily suggest a lower risk of stroke with high dose but also a higher risk of bleeding with high dose. Apixaban versus no anticoagulation was compared in one cohort study and did not lower the risk of stroke compared with non-treated regardless of apixaban dosage. Widespread use of NOACs in dialysis patients is limited by adequately sized RCTs. Available evidence suggests a potential for use of apixaban and rivaroxaban in reduced dose.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Renal Dialysis; Rivaroxaban; Stroke; Vitamin K

One of the most catastrophic complications of Atrial fibrillation (AF) is thromboembolic stroke. Current guidelines recommend that 3 weeks of anticoagulation is adequate prior to direct current cardioversion (DCCV) to prevent thromboembolism. Here we present data regarding, which anticoagulant is most likely to show a presence of an Left atrial appendage thrombus (LAAT) on trans esophageal echocardiogram (TEE) for DCCV despite 3 weeks of anticoagulation.. To investigate the effectiveness of both vitamin k antagonist (VKA) and direct oral anticoagulants (DOAC) in patients with AF as an anticoagulant for LAAT after 3 weeks of medication.. This is a single-high volume tertiary center, where TEE precardioversion is the standard practice. We reviewed data over 10 months where DCCV was intended on individuals with AF who were fully anticoagulated for at least 3 weeks with either a VKA or taking a DOAC.. The data showed a statistical difference between patients who were fully anticoagulated for at least 3 weeks with VKA in comparison to DOACs. Patients on DOACs are significantly less likely to have an LAAT after at least 3 weeks of anticoagulation. OR = 0.04 (CI 95% 0.005-0.42; p-value < .05). Despite anticoagulation for at least 3 weeks, 40% of our patients still had a LAAT.. Our data indicates that all patients should be required to undergo a TEE prior to DCCV. This data also adds to the current evidence and supports the use of DOAC in AF to prevent LAAT.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Electrocardiography; Fibrinolytic Agents; Heart Diseases; Humans; Incidence; Thrombosis; Vitamin K

Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs.. Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used.. We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA.. Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dabigatran; Humans; Intracranial Hemorrhages; Ischemic Stroke; Pyridones; Rivaroxaban; Stroke; Thromboembolism; Vitamin K

Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein thromboembolism. However, the optimal type of OAC strategy (direct oral anticoagulants, DOACs, or vitamin K antagonists, VKA) is still unclear in this setting.. We performed systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies reporting either all-cause mortality, major/life-threatening bleeding or stroke events.. Ten observational studies and two randomized controlled trials (RCTs) including a total of 29,485 patients were eligible for inclusion. Compared to VKA, DOACs use after TAVR was associated with a modest but significantly lower rates of all-cause mortality (RR 0.90; 95% CI: 0.81-0.99, p-value 0.04) with results mainly driven by observational studies. Cardiovascular mortality (RR 1.03; 95% CI: 0.81-1.30; p-value 0.84), total stroke events (RR 0.97; 95% CI: 0.76-1.23, p-value 0.79), major/life-threatening bleeding (RR 0.93; 95% CI: 0.72-1.21, p-value 0.61) and minor bleeding (RR 0.96; 95% CI: 0.74-1.23; p-value 0.72) were similar between VKA and DOACs.. Considering the totality of available evidence, in patients who underwent TAVR with a concomitant indication for OAC, DOACs-based strategy is an effective and safe anticoagulation strategy compared to VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

For a long time, vitamin K antagonists (VKA) were the only oral anticoagulation therapy available to reduce adverse events in atrial fibrillation (AF) patients. Direct-acting oral anticoagulants (DOAC) are at least as effective and safe as VKA with few drug interactions, rapid onset, and short half-life. Four DOACs, dabigatran, apixaban, rivaroxaban, and edoxaban, have demonstrated efficacy and safety for treatment in AF patients.. The purpose of this review article is to analyze the current evidence in clinical trials and in real-world populations and performed a new analysis with the estimated effect of those DOACs over the VKA population from the FANTASIIA registry.. In the absence of randomized, controlled head-to-head comparisons between DOACs, high-quality observational data can provide useful information on the comparative effectiveness of DOACs. Current clinical guidelines recommend the management of oral anticoagulation in AF patients with DOACs over VKA for stroke prevention; however, many guidelines generally do not suggest a specific DOAC choice in clinical practice. The revised evidence in this manuscript and our real experience reflects that apixaban and dabigatran show the best efficacy and safety profile.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pyridones; Registries; Rivaroxaban; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Transcatheter Aortic Valve Replacement; Vitamin K

Obesity is an epidemic with rising prevalence, and obese patients are predisposed to comorbid conditions that increase risk for thromboembolic events. It is critical to identify safe and effective anticoagulation therapy for use in this population. Direct oral anticoagulants (DOACs) are a preferred option for anticoagulation in patients of normal weight due to many benefits and equivalent safety and efficacy to their vitamin K antagonist counterparts. However, the safety and efficacy of DOACs in obese patients is not well understood. This review describes recent studies on the pharmacokinetics, safety and efficacy, and clinical outcomes of the DOACs apixaban, rivaroxaban, edoxaban and dabigatran in obese patient populations. DOACs may be a beneficial alternative to vitamin K antagonist therapy in obese patient populations.. The incidence of obesity within the USA is on the rise, as is that of the medical conditions that often accompany it. These include conditions that can predispose individuals to forming clots in the blood, such as atrial fibrillation, which is a form of an abnormal heartbeat, and nonalcoholic fatty liver disease, which is caused by fat buildup around the liver. Therefore, it is important that we have effective medicines that can prevent clotting in an obese patient population. Direct oral anticoagulants are a new, preferred medication option for this, but it is unclear how safe or effective they are in obese people; there is some concern that because of increased body weight, individuals may not get enough medicine to effectively prevent clots from forming, which would ultimately put them at risk for clotting and serious adverse health outcomes such as stroke. This review describes recent studies on the use of the direct oral anticoagulants apixaban, rivaroxaban, edoxaban and dabigatran in obese patients, and whether they are a safe and effective form of anticoagulation in this population.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Body Mass Index; Body Weight; Dabigatran; Hemorrhage; Humans; Obesity; Pyridones; Rivaroxaban; Stroke; Vitamin K

This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants.. This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists.. A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001].. This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Rivaroxaban; Tramadol; Vitamin K

Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes.. We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool.. Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8-2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24-3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6-7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs.. Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Embolism; Hemorrhage; Hemorrhagic Stroke; Humans; Hypertension; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Vitamin K

Previous meta-analyses comparing major bleeding of uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) versus uninterrupted vitamin K antagonist (VKA) during catheter ablation (CA) of atrial fibrillation (AF) had no consensus. This meta-analysis was performed to comprehensively evaluate the risk of major bleeding events of these two anticoagulant strategies.. We searched online databases for randomised controlled trials that compared major bleeding events of uninterrupted NOACs and VKA during CA of AF. A fixed-effect model was used if. Six studies including 2392 patients were included in the analysis. The incidence of major bleeding was lower in the NOACs group than in the VKA group (OR = 0.56, 95% CI = 0.34 - 0.93,. This meta-analysis suggests that compared to uninterrupted VKA, uninterrupted NOACs are superior in major bleeding during CA of AF, but this superiority existed only in the aspect of severe puncture site complications.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Vitamin K

Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials.. We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients.. A systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020.. Three retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42-0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57-0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40-0.59; p < 0.001).. Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Liver Cirrhosis; Retrospective Studies; Stroke; Vitamin K

Obesity is associated with increased risks of atrial fibrillation (AF) and venous thromboembolism (VTE) for which anticoagulation is commonly used. However, data on the efficacy and safety of oral anticoagulants in patients with morbid obesity are limited.. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) for AF or VTE in patients with morbid obesity.. Patients with morbid obesity on DOACs had similar risks of stroke/systemic embolism, lower rates of recurrent VTE, and major bleeding events compared to those on VKAs. However, the certainty of evidence was low given that studies were mostly observational with high risk of confounding.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Obesity, Morbid; Stroke; Venous Thromboembolism; Vitamin K

Current guidelines give class I recommendations for uninterrupted use of dabigatran rivaroxaban as an alternative to vitamin K antagonist (VKA) in patients of atrial fibrillation (AF) who are undergoing catheter ablation. The recent randomized controlled trials have shown similar efficacy of novel oral anticoagulants when compared to VKA in these patients. We sought to perform a meta-analysis with a focus on subgroup analysis of novel oral anticoagulants.. We searched PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through August 2020. Six RCTs studies (n = 2260) comparing the use of NOACs versus VKA in patients with AF undergoing catheter ablation were included. The odds ratio (OR) with 95% confidence interval was computed and P < 0.05 was considered as a level of significance. Major adverse cardiac events (MACE) were considered as a primary endpoint.. Our results showed a significant difference in MACE between NOACs and VKA [OR 0.57 (0.37-0.88); P = 0.01] and in major bleeding events [OR 0.55 (0.35-0.86); P = 0.009], which is mainly derived from the use of dabigatran. No significant difference in MACE or major bleeding events was found on the subgroup analysis of rivaroxaban and apixaban over VKA therapy.. Uninterrupted use of NOACs is safe and effective alternative for the prevention of cerebral thromboembolism and reducing the risk of major bleeding in patients undergoing catheter ablation of AF. However, the individual subgroup analysis showed that only dabigatran is superior to VKA in terms of reducing MACE through a reduction in major bleeding. The rivaroxaban, apixaban and edoxaban are non-inferior to VKA therapy based on these results. Further studies are needed to generalize these recommendations in morbidly obese patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Obesity, Morbid; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

In the year 2021 we celebrate the 80th anniversary of the first clinical use of vitamin K antagonists (VKAs), the mainstay of prevention and long-term treatment of thromboembolic disease. The discovery and development of oral anticoagulants is one of the most important chapters in the history of medicine, a goal pursued by physicians trying to combat the clinical manifestations of thrombosis since ancient times. Until the last decade, VKAs were the only oral anticoagulants available and used in clinical practice. Today, their clinical use has progressively shrunk, as the non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly replacing VKAs in various conditions after the successful completion of several large randomized controlled trials. Currently, new research is tackling upstream components of the intrinsic pathway - particularly factor XI and factor XII - for the development of new, even safer anticoagulants promising to reduce bleeding without compromising efficacy. This review highlights the evolution of oral anticoagulant therapy tracing the key stages of a long and fascinating history that has unfolded from the first part of the twentieth century until today, indeed an intriguing journey where serendipity is intertwined with the tenacious work of many researchers.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Thromboembolism; Vitamin K

Real-life data about the use of dabigatran in patients with non-valvular atrial fibrillation are warranted. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of dabigatran, globally and stratified by dose (110/150 mg twice daily), vs vitamin K antagonists in non-Asian patients with non-valvular atrial fibrillation from "real-world" studies.. A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement) statement. The ROBINS-I tool was used to assess bias risk. MEDLINE and EMBASE, from inception up to May 2021, using appropriate controlled vocabulary and free search terms, were searched.  RESULTS: A total of 34 studies, corresponding to 37 articles involving 1,600,722 participants (1,154,283 exposed to vitamin K antagonists and 446,439 to dabigatran) were eligible for this review. Dabigatran 150 mg reduced the risk of ischemic stroke compared with vitamin K antagonists, with a 14% risk reduction (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.74-0.98). Globally, dabigatran reduced the risk of all-cause mortality compared with vitamin K antagonists (HR 0.76, 95% CI 0.69-0.84), with a greater effect observed with dabigatran 150 mg (HR 0.65, 95% CI 0.58-0.73). There was a trend towards a lower risk of myocardial infarction with dabigatran 150 mg (HR 0.86, 95% CI 0.71-1.04). Regarding the primary safety outcomes, dabigatran (either at a dose of 150 mg or 110 mg) reduced the risk of major bleeding compared with vitamin K antagonists (HR 0.77, 95% CI 0.70-0.83), as well as the risk of intracranial bleeding (HR 0.44, 95% CI 0.39-0.50) and fatal bleeding (HR 0.76, 95% CI 0.60-0.95), but with a slight increase in gastrointestinal bleeding risk (HR 1.16, 95% CI 1.08-1.26).. Dabigatran has a favorable impact on effectiveness and safety outcomes compared with vitamin K antagonists in real-world populations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Stroke; Vitamin K

The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly patients with atrial fibrillation (AF) and indirectly compare NOACs in this population.. MEDLINE, Cochrane, ISI Web of Sciences, and SCOPUS were searched for randomized or adjusted observational studies comparing NOACs vs. VKAs for stroke prevention in AF patients ≥75 years. The primary efficacy and safety outcomes of this meta-analysis were the composite of stroke and systemic embolism (SSE) and major bleedings, respectively. Other secondary outcomes were also analysed. The analysis included 22 studies enrolling 440 281 AF patients ≥ 75 years. The risk of SSE was significantly lower with NOACs vs. VKAs [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.70-0.89], whereas no differences were found for major bleedings (HR 0.94; 95% CI 0.85-1.05). NOACs reduced the risk of intracranial bleeding (HR 0.46; 95% CI 0.38-0.58), haemorrhagic stroke (HR 0.61; 95% CI 0.48-0.79) and fatal bleeding (HR 0.46; 95% CI 0.30-0.72) but increased gastrointestinal (GI) bleedings (HR 1.46; 95% CI 1.30-1.65), compared to VKAs. The adjusted indirect comparison showed no significant differences in term of SSE between NOAC agents. Conversely, the risk of major bleeding was higher for rivaroxaban vs. apixaban (HR 1.69; 95% CI 1.39-2.08) and edoxaban (HR 1.37; 95% CI 1.14-1.67), and for dabigatran vs. apixaban (HR 1.47; 95% CI 1.18-1.85).. In elderly patients with AF, NOACs are associated to a lower risk of SSE, intracranial bleeding, haemorrhagic stroke and fatal bleeding than VKAs, but increase GI bleedings. In this analysis, the safety profile of individual NOAC agents was significantly different.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Vitamin K

Periprocedural uninterrupted anticoagulation for catheter ablation of atrial fibrillation (AF) became standard after positive results of vitamin K antagonist (VKA) trials. Previous studies of uninterrupted direct oral anticoagulants (DOACs) vs. VKA have given controversial results. We thus aimed to elucidate the risk/benefit ratio of uninterrupted DOAC vs. VKA during catheter ablation of AF in an updated meta-analysis of randomised controlled trials (RCTs).. Online databases were searched for RCTs comparing uninterrupted DOAC to VKA in patients undergoing catheter ablation of AF. Data from retrieved studies were analysed in a comprehensive meta-analysis. Primary safety outcome was major bleeding; primary efficacy outcome was stroke or transient ischaemic attack (TIA). Secondary outcomes included a composite of major bleeding and stroke or TIA, minor bleeding, acute cerebral lesions on magnetic resonance imaging (MRI), and mortality.. Six eligible RCTs comprising 2,369 patients were included. There were no significant differences in DOAC vs. VKA concerning the rates of major bleeding (2.2% vs. 3.8%; odds ratio (OR) 0.69, 95% confidence interval (CI) 0.30-1.56;. Our meta-analysis suggests that uninterrupted DOAC is not superior to VKA in patients undergoing catheter ablation of AF with comparable rates of major bleeding and stroke.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Hemorrhage; Humans; Risk Factors; Stroke; Vitamin K

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have traditionally received triple antithrombotic therapy (TAT) consisting of aspirin and a P2Y

Topics: Aspirin; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Vitamin K

The ideal periprocedural anticoagulation strategy for patients being treated with a novel oral anticoagulant (NOAC) during catheter ablation (CA) for atrial fibrillation (AF) is unclear. We evaluated the safety and efficacy of using a minimally interrupted NOAC strategy versus an uninterrupted NOAC or vitamin K antagonist (VKA) strategy during AF ablation.. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled or prospective observational studies that compared a minimally interrupted NOAC strategy with an uninterrupted NOAC or VKA strategy from the time of database establishment up to December 2019. The primary endpoints were major bleeding, minor bleeding, and symptomatic thromboembolism. The secondary endpoint was silent cerebral infarction (SCI) as detected by post-ablation brain magnetic resonance imaging (MRI). A measurement of treatment effect for the endpoint was reported as pooled odds ratio (OR) with 95% confidence interval (CI).. A total of 18 studies (6 randomized, 11 observational, and 1 randomized registry) with 6203 patients were included in the final analysis (47% of the patients received minimally interrupted NOAC). There was no significant difference between treatment groups regarding the risk for major bleeding (OR 1.04, 95% CI 0.69-1.57, P = 0.86, I. A periprocedural anticoagulation strategy of minimally interrupted NOAC is not superior to uninterrupted NOAC or VKA when used during AF ablation. There is evidence favoring the use of uninterrupted NOAC or VKA in terms of the risk for SCI.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Vitamin K

The need for anticoagulation in patients with atrial fibrillation (AF) is fundamental to prevent thromboembolic events. Direct oral anticoagulants (DOACs) recently demonstrated to be superior, or at least equal, to Warfarin in reducing the risk for stroke/systemic embolism and preventing major bleeding and intracranial hemorrhages. The AF population often suffers from chronic kidney disease (CKD). Indeed, the relationship between AF and renal function is bidirectional: AF can trigger kidney failure, while kidney impairment can promote alterations able to enhance AF. Therefore, there are concerns regarding prescriptions of anticoagulants to patients with AF and CKD. The worsening in kidney function can be effectively due to anticoagulants administration. Warfarin has been recognized to promote acute kidney injury in case of excessive anticoagulation levels. Nevertheless, further mechanisms can induce the chronic worsening of renal function, thus leading to terminal kidney failure as observed in post-hoc analysis from registration trials and dedicated observational studies. By contrast, DOACs seem to protect kidneys from injuries more efficiently than Warfarin, although they still continue to play a role in promoting some kidney lesions. However, the exact mechanisms remain unknown. This narrative review aimed to discuss the influence of oral anticoagulants on renal impairment as well as to overview potential pathophysiological mechanisms related to this clinical complication.

Topics: Anticoagulants; Atrial Fibrillation; Cytochrome P-450 Enzyme System; Factor Xa Inhibitors; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Oxidative Stress; Patient Acuity; Stroke; Vitamin K

Atrial fibrillation (AF) represents the arrhythmia of greatest clinical impact and catheter ablation of AF (CAAF) has become the most effective strategy for rhythm control in selected patients. Therefore, appropriate anticoagulation strategies are of paramount importance for patients undergoing CAAF, especially those at high risk, such those with high CHA2DS2VASc scores. Optimal management of anticoagulation before, during, and after CAAF is crucial. Several studies have evaluated the use of different anticoagulation strategies in the periprocedural period. Randomized controlled trial seem to suggest that in patients undergoing CAAF, uninterrupted (or minimally interrupted) direct oral anticoagulants (DOACs) provides an alternative to continuous vitamin K antagonists strategy, with low thromboembolic and bleeding risk.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Vitamin K

Atrial fibrillation (AF) and chronic kidney disease (CKD) are closely related conditions with shared risk factors. The growing prevalence of both AF and CKD indicates that more patients will suffer from concurrent conditions. There are various complex interlinking mechanisms with important implications for the management of these patients. Furthermore, there is uncertainty regarding the use of oral anticoagulation (OAC) in AF and CKD that is reflected by a lack of consensus between international guidelines. Therefore, the importance of understanding the implications of co-existing AF and CKD should not be underestimated. In this review, we discuss the pathophysiology and association between AF and CKD, including the underlying mechanisms, risk of thrombo-embolic and bleeding complications, influence on stroke management, and evidence surrounding the use of OAC for stroke prevention.

Topics: Action Potentials; Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Heart Conduction System; Heart Rate; Humans; Kidney; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Brain Ischemia; COVID-19; Drug Monitoring; Drug Substitution; Factor Xa Inhibitors; Humans; Inpatients; Prognosis; SARS-CoV-2; Thrombophilia; Venous Thromboembolism; Vitamin K

Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established.. We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF.. An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users.. The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52-0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74-0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52-0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50-0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47-0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78-1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78-1.06; p 0.24).. In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Treatment Outcome; Vitamin K

Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk.. PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian-Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75-0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71-0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60-0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74-1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs.. This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Stroke; Vitamin K

 To undertake a systematic review and meta-analysis to assess the satisfaction of patients receiving nonvitamin K anticoagulants (NOACs), compared with vitamin K antagonists (VKAs)..  We searched CENTRAL, MEDLINE, Embase, and Clinicaltrials.gov for randomized controlled trials (RCTs) and observational studies. Two reviewers screened, extracted, and appraised data independently. We pooled data using a random-effects model. Outcome included treatment satisfaction, which was assessed by scores of Duke Anticoagulation Satisfaction Scale (DASS), Anticlot Treatment Scale (ACTS), Perception of Anticoagulant Treatment Questionnaire 2 (PACT-Q2), or Treatment Satisfaction Questionnaire for Medication version II (TSQM-VII) and their domains reported with 95% confidence intervals (95% CIs). We followed MOOSE and PRISMA guidelines..  In patients with nonvalvular atrial fibrillation or venous thromboembolism, NOAC treatment is associated with greater satisfaction compared with VKAs. The switch from VKAs to NOACs was associated with improved patients' satisfaction. These effects were largely due to a lower degree of treatment burden with NOAC treatment.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Patient Satisfaction; Thrombosis; Treatment Adherence and Compliance; Venous Thromboembolism; Vitamin K

Clinical trials have assessed the effect of direct oral antagonists (DOACs) in patients with atrial fibrillation (AF) after percutaneous coronary interventions (PCI). Studies were designed to test the effect on bleeding incidence, but concerns related to safety on ischemic events remain.. We performed a meta-analysis with currently available studies involving DOACs versus Vitamin-K antagonist (VKA) in patients with AF after PCI. The primary endpoint was the incidence of cardiac ischemic events, including myocardial infarction and stent thrombosis. Secondary endpoints were the incidence of stroke, all-cause mortality, and major bleeding.. Eleven thousand twenty-three patients were included in the analysis: 5510 receiving DOACs and 5513 VKA. A total of 190 cases of myocardial infarction were registered in patients treated with DOACs and 177 in patients on VKA, and no statistical difference was noted [relative risk (RR): 1.07 95% confidence interval (CI) 0.88-1.31]. The incidence of stent thrombosis was very low with no differences between both treatment strategies (RR: 1.14 95% CI 0.76-1.71). The incidence of cardiac ischemic events was the same in patients receiving DOACs or VKA (HR 1.09 95% CI 0.91-1.30). No differences were observed in the incidence of stroke (RR: 0.86 95% CI 0.61-1.23) or mortality (RR: 1.09, 95% CI 0.90-1.31). Treatment with DOACs was associated with 34% reduction in major bleeding (RR: 0.66, 95% CI 0.54-0.81).. Treatment with DOACs in patients with AF after a PCI do not increase the risk of cardiac ischemic events, stroke, or death and reduce the incidence of major bleeding by 34% as compared with VKA.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Thrombosis; Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Risk Assessment; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome; Vitamin K

Guidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Fibrinolytic Agents; Humans; Practice Guidelines as Topic; Thromboembolism; Vitamin K

Effective stroke prevention with oral anticoagulation (OAC) reduces the risk of stroke and death among patients with atrial fibrillation (AF). For most patients with AF, treatment options include vitamin K antagonists (VKA) or non-vitamin K antagonist oral anticoagulants (NOACs). NOACs have been introduced as an alternative to VKAs, and their use has been steadily increasing in the United Kingdom and Europe over a decade. In randomized clinical trials, NOACs had a favorable risk-benefit profile as compared to warfarin. However, there is a concern about their long-term safety in clinical practice, especially in high-risk patients. There have been a number of registries and surveys based on the real-world patients with AF which has been conducted and published, providing data on contemporary AF management.. In this narrative review, the authors discuss current trends in the use of OAC in the United Kingdom and Europe, considering the potential directions for future anticoagulant therapy in patients with AF.. The increasing prevalence of AF and AF-related comorbidities proves the need for comprehensive prevention and management strategies. The challenge is the optimization of therapy for each patient. However, there are still gaps in optimal stroke prevention, and the mortality rates remain high in patients with AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Europe; Humans; Stroke; United Kingdom; Vitamin K

The increasing availability of real-world evidence (RWE) about safety and effectiveness of direct non-vitamin K oral anticoagulants (DOACs) for the management of atrial fibrillation (AF) offers the opportunity to better understand the clinical and economic implications of DOACs versus vitamin K antagonists (VKAs). The objective of this study was to compare the economic implications of DOACs and VKAs using data from real-world evidence in patients with AF.. A Markov model simulating the lifetime course of patients diagnosed with non-valvular AF was used to evaluate the cost-effectiveness of DOACs (i.e., rivaroxaban, dabigatran and apixaban) versus VKAs from the Italian National Health System (INHS) perspective. The model was made up of data from the literature and a meta-analysis of RWE on the incidence of stroke/systemic embolism (SE), major bleeding (MB), intracranial haemorrhage (ICH) and all-cause mortality (ACM); direct costs included drug costs, costs for drug monitoring, and management of events from official national lists. One-way and probabilistic sensitivity analyses (PSA) were used to assess the robustness of the results.. Results from the meta-analysis showed that apixaban had a high probability of being the most effective for stroke/SE, MB and ACM. Despite their higher acquisition costs, the cost-effectiveness analysis showed all DOACs involved a saving when compared with VKAs, with per-patient savings ranging between €4647 (rivaroxaban) to €6086 (apixaban). Moreover, all DOACs indicated a gain both in quality-adjusted life-years and life-years. According to PSA, findings related to apixaban were consistent, while for dabigatran and rivaroxaban PSA revealed a higher degree of uncertainty.. The beneficial effect of DOACs on containing events showed in RWE had the potential to offset drug-related costs, thus improving the sustainability of treatment for non-valvular AF in daily clinical practice.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Female; Hemorrhage; Humans; Italy; Male; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Vitamin K

Although several studies have assessed the effect of non-vitamin K antagonist oral anticoagulants (NOACs) relative to that of vitamin K antagonists (VKAs) in patients with left ventricular thrombus, the results remain controversial. Herein, a meta-analysis was performed to compare the effectiveness and safety of NOACs versus VKAs for the treatment of left ventricular thrombus. We systematically searched the Cochrane Library, PubMed and Embase databases until November 2020 for studies that compared the effects of NOACs versus VKAs in patients with left ventricular thrombus. The treatment effects were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) and pooled by a random-effects model. Seven retrospective studies involving 865 patients with left ventricular thrombus (266 NOAC and 599 VKA users) were included. The pooled analysis suggested no difference in the rate of thrombus resolution between the NOAC and VKA groups (OR = 0.83, 95% CI 0.61-1.13). There were also no differences in the rates of stroke or systemic embolism (OR = 0.62, 95% CI 0.20-1.97), bleeding events (OR = 0.73, 95% CI 0.37-1.45), or all-cause death (OR = 0.92, 95% CI 0.50-1.69) between patients treated with NOACs and those treated with VKAs. In addition, the rates of thrombus resolution, stroke or systemic embolism, bleeding events, and all-cause death between NOAC- and warfarin-treated patients were also similar. Our current evidence suggested that NOAC and VKA users had similar rates of thrombus resolution and clinical outcomes among patients with left ventricular thrombus. Further large-scale prospective studies should confirm our results.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Prospective Studies; Retrospective Studies; Stroke; Thrombosis; Vitamin K

In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI).. Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis.. A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84-1.20; P = .98), mortality (RR: 1.08, 95% CI: 0.78-1.48; P = .66), myocardial infarction (RR: 1.02, 95% CI: 0.74-1.42; P = .90), stroke (RR: 0.94, 95% CI: 0.53-1.67; P = .84) and stent thrombosis (RR: 1.09, 95% CI: 0.56-2.10; P = .80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54-0.82; P = .0001), total minor bleeding (RR: 0.74, 95% CI: 0.64-0.85; P = .0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35-0.95; P = .03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42-0.92; P = .02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13-0.95; P = .04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51-0.90; P = .008) were significantly higher with TT.. DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.

Topics: 4-Hydroxycoumarins; Aged; Aspirin; Atrial Fibrillation; Diabetes Mellitus; Diabetic Cardiomyopathies; Drug Therapy, Combination; Female; Hematologic Agents; Humans; Indenes; Male; Observational Studies as Topic; Percutaneous Coronary Intervention; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Renal Insufficiency, Chronic; Stroke; Vitamin K

Several observational studies have compared the effectiveness and safety outcomes between nonvitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with a history of either stroke/transient ischemic attack (TIA) or intracranial hemorrhage. Therefore, our current meta-analysis aimed to address this issue. The Cochrane Library, PubMed, and Embase databases were systematically searched until December 2020 for all relevant observational studies. We applied a random-effects model to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for this meta-analysis. A total of 10 studies were included. Among patients with a history of stroke/TIA, the use of NOACs versus VKAs was associated with decreased risks of stroke (HR, 0.82, 95% CI 0.69-0.97), systemic embolism (HR, 0.73, 95% CI 0.61-0.87), all-cause death (HR, 0.87, 95% CI 0.81-0.94), major bleeding (HR, 0.77, 95% CI 0.64-0.92) and intracranial hemorrhage (HR, 0.54, 95% CI 0.38-0.77). Among patients with a history of intracranial hemorrhage, the use of NOACs versus VKAs was associated with reduced risks of stroke (HR, 0.81, 95% CI 0.68-0.95), all-cause death (HR, 0.68, 95% CI 0.49-0.94), and intracranial hemorrhage (HR, 0.66, 95% CI 0.51-0.84). Compared with VKAs, the use of NOACs exhibited superior efficacy and safety outcomes in AF patients with previous stroke/TIA, and the use of NOACs was associated with reduced risks of stroke, all-cause death, and intracranial hemorrhage in patients with a history of intracranial hemorrhage.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

At present, there are no guideline recommendations for minimally interrupted use of non-vitamin K antagonist oral anticoagulants (mi-NOAC) during catheter ablation (CA) for atrial fibrillation (AF). Current evidence is predominantly based on observational studies, with continuous use of vitamin K antagonist in the control arm. This quantitative summary reflects the first high-level evidence on contemporary regimens, with continuous NOAC use (c-NOAC) as the current gold standard.. Meta-analysis (Pubmed, Embase, and Web of Science) on prospective, controlled studies comparing contemporary mi-NOAC (without bridging) with c-NOAC. Net adverse clinical events (major bleeding, thrombo-embolic events) were the primary outcome. In addition, we analysed total bleeding, minor bleeding, and silent cerebral embolism. Eight studies (six randomized, two observational) with 2168 patients were summarized. The primary endpoint occurred in 1.0% (18/1835): 1.1% (11/1005) vs. 0.8% (7/830) for the mi-NOAC and c-NOAC groups, respectively; odds ratio (OR) 1.20 [95% confidence interval (CI) 0.49-2.92, P = 0.64]. The OR for total bleeding on mi-NOAC was 1.26 (95% CI 0.97-1.63, P = 0.07). ORs for minor bleeding and silent cerebral embolism were 1.17 (95% CI 0.80-1.70, P = 0.34) and 2.62 (95% CI 0.54-12.61, P = 0.12), respectively.. This synopsis provides a quantitative synthesis of high-level evidence on a contemporary strategy of mi-NOAC in CA for AF, and overall clinical outcomes were not different from continuous NOAC use. Despite preprocedural interruption, there was no sign of lower bleeding rates. Additional higher volume datasets are warranted for more precise treatment effect estimations of this everyday alternative anticoagulation strategy in AF ablation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Stroke; Vitamin K

To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial fibrillation (AF) and bioprosthetic heart valve replacement or repair.. A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews and Google scholar databases. Studies that were done in patients with AF who underwent bioprosthetic heart valve replacement or repair and that compared the outcomes between the use of direct-acting oral anticoagulants (DOACs) and vitamin K antagonists were eligible for inclusion. Studies that were preferably randomized controlled trials or adopted a cohort approach or retrospective data-based studies were considered for inclusion. The strength of association was presented in the form of pooled hazards risk (HR). Statistical analysis was done using STATA version 16.0.. A total of 8 articles were included in the meta-analysis. There were no significant differences in the risk of "all-cause stroke" [HR 0.72, 95% CI: 0.39, 1.34] and ischemic stroke [HR 0.79, 95% CI: 0.49, 1.29] between the two groups. The risk of "any bleeding" [HR 0.74, 95% CI: 0.64, 0.87], major bleeding [HR 0.60, 95% CI: 0.42, 0.86] and intra-cranial bleeding [HR 0.54, 95% CI: 0.36, 0.81] was much lower in those that received DOAC compared to warfarin. Compared to those receiving warfarin, those on DOACs had substantially reduced risk of any clinical thromboembolic events [HR 0.52, 95% CI: 0.39, 0.70]. No significant differences were noted for all-cause mortality [HR 0.88, 95% CI: 0.74, 1.05], cardiovascular events/myocardial infarction (MI) [HR 0.58, 95% CI: 0.33, 1.04] and and readmission rates [HR 0.85, 95% CI: 0.62, 1.18].. Findings suggest that the use DOACs in patients with AF with bioprosthetic valve replacement or repair is comparatively better than vitamin K antagonists in reducing the risk of bleeding and thrombo-embolic events. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heart Valves; Humans; Vitamin K

This systematic review and meta-analysis compares direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with atrial fibrillation and bioprosthetic valve replacement or repair (BVR).. The optimal anticoagulation therapy for patients with atrial fibrillation and a history of bioprosthetic valve replacement or repair (BVR) is not well understood.. We performed a systematic literature review to identify clinical studies that compared anticoagulation therapies for patients with atrial fibrillation and BVR. The primary outcomes of stroke, major bleeding, and mortality were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data is public.. Our search yielded 101 potential studies. We included six studies reporting on 1911 patients. There was a lower risk of stroke and major bleeding in patients with atrial fibrillation after BVR treated with DOACs when compared to VKAs with risk ratios of 0.44 (95% CI 0.24-0.82, p < 0.01) and 0.53 (95% CI 0.34-0.83, p < 0.01), respectively. There was no statistically significant difference in mortality between patients with atrial fibrillation after BVR treated with DOACs compared to patients treated with VKAs with a risk ratio of 1.12 (95% CI 0.73-1.74, p = 0.60).. This systematic review and meta-analysis suggests that DOACs are superior to VKAs with respect to stroke and major bleeding in patients with atrial fibrillation and BVR.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Treatment Outcome; Vitamin K

The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population.. We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).. A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66-0.93), major bleeding (RR 0.68, 95% CI 0.53-0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41-0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57-1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61-1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37-0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38-0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.97) compared with warfarin.. Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Liver Diseases; Stroke; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Humans; Stroke; Vitamin K

In the last 40 years, concern about the obesity epidemic has increased. Data from the current literature highlight a strong relationship between obesity and atrial fibrillation (AF), particularly in relation to an increased risk for incident and recurrent AF. A phenomenon called the "obesity paradox" has emerged: the apparently counterintuitive evidence from epidemiological data indicating that overweight and obese patients may have a better prognosis than healthy-weight patients. A differential impact of oral anticoagulants (OACs) in terms of effectiveness and safety in the various body mass index categories has been postulated, particularly in the comparison between non-vitamin-K antagonist oral anticoagulants and vitamin K antagonists. This review aims to summarize the evidence on the impact of obesity in patients with AF, focusing on descriptions of the obesity paradox and its relationships with OAC treatment.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Obesity; Overweight; Prognosis; Risk Factors; Vitamin K

Direct Oral Anticoagulants (DOACs) consistently demonstrated a greater net clinical benefit compared to Vitamin K Antagonists (VKAs) also in persons aged 75 years and over, who account for the largest proportion of AF patients; however, major uncertainties in DOACs prescription have to do with this age group. In this review, persistent uncertainties and implications of frailty and geriatric syndromes on DOACs prescription, and practical use of DOACs in real-world older persons, and will be discussed.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Humans; Vitamin K

 In this study-level meta-analysis, we evaluated the clinical outcome with nonvitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with cancer..  Anticoagulation in AF patients with cancer is challenging given the coexistence of elevated thrombotic and bleeding risk. The efficacy and safety of NOACs in this setting remain unclear..  We included three randomized trials in our primary analysis (.  In AF patients with malignancy, NOACs appear at least as effective as VKAs in preventing thrombotic events and reduce intracranial bleeding. NOACs may represent a valid and more practical alternative to VKAs in this setting of high-risk patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Data Interpretation, Statistical; Embolism; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Observational Studies as Topic; Odds Ratio; Patient Safety; Randomized Controlled Trials as Topic; Risk; Risk Factors; Stroke; Thromboembolism; Venous Thromboembolism; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs), or direct oral anticoagulants have not been tested in randomized trials conducted in patients with atrial fibrillation (AF), who had malignant disease. However, their use in cancer patients increases and real-life evidence for their effectiveness and safety in this vulnerable subset of patients is growing. The challenges of the use of NOACs in cancer patients with AF and the current expert opinions on this subject have been summarized in this review article.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Neoplasms; Vitamin K

Atrial fibrillation (AF) is a common co-morbidity in patients undergoing transcatheter aortic valve implantation (TAVI), but whether direct oral anticoagulants (DOACs) confer similar safety and efficacy compared with vitamin K antagonist (VKA) remains unclear in this population. The aim of our study was to investigate the safety and efficacy of DOACs compared with VKA in patients undergoing TAVI with concomitant indication of oral anticoagulation. PUBMED and EMBASE were searched through October 2019 for studies comparing DOACs versus VKA in patients undergoing TAVI with indication of oral anticoagulation. The main efficacy outcomes were all-cause mortality and stroke whereas the main safety outcome was major and/or life-threatening bleeding. Our search identified 5 eligible studies including 2,569 patients. Majority of patients had atrial fibrillation as indication of anticoagulation. There were no significant differences in all-cause mortality, major and/or life-threatening bleeding, and stroke in patients treated with DOACs versus VKA (odds ratio [OR] 1.07, 95% confidence interval [CI] [0.73 to 1.57], p = 0.72, OR = 0.85, 95% CI [0.64 to 1.12], p = 0.24, OR 1.52, 95% CI [0.93 to 2.48], p = 0.09, respectively). In conclusion, in patients undergoing TAVI with concomitant indication for oral anticoagulation, all-cause mortality, major and/or life-threatening bleeding, and stroke were similar between DOACs and VKA. Further large scale randomized controlled trials are needed to search the optimal oral anticoagulation regimen in this population.

Topics: Administration, Oral; Anticoagulants; Aortic Valve Stenosis; Atrial Fibrillation; Comorbidity; Fibrinolytic Agents; Humans; Postoperative Period; Stroke; Transcatheter Aortic Valve Replacement; Vitamin K

The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective.. A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers.. In the base-case analysis, the incremental total cost was €714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were €6,006 and €4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates.. Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Female; France; Humans; Male; Markov Chains; Middle Aged; Myocardial Infarction; Quality-Adjusted Life Years; Rivaroxaban; Stroke; Vitamin K; Warfarin

Catheter ablation (CA) of atrial fibrillation (AF) is an important rhythm control strategy for patients with drug-refractory AF. We aimed to perform an updated meta-analysis of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs) as uninterrupted anticoagulation in patients undergoing AF ablation to assess safety and efficacy of DOAC, after the publication of recent data on edoxaban in CA of AF.. We performed a meta-analysis of RCTs enrolling patients undergoing AF ablation. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for thromboembolic events, major bleeding (MB), and non-major bleeding (NMB).. A total of 2118 patients have been included in the analysis. Compared with patients receiving VKA, patients receiving DOACs had a lower, although non-significant, risk of thromboembolic events (RR, 0.40; 95% CI, 0.09-1.76; P = 0.23). MB rates in patients treated with DOACs were statistically significantly lower than VKA (RR, 0.61; 95% CI, 0.39-0.93, P = 0.02). The incidence of NMB was not significantly different (RR, 0.98; 95% CI, 0.83-1.57, p n.s.).. In a meta-analysis of RCTs, an uninterrupted DOACs strategy for CA of AF appears to be superior to uninterrupted VKA in terms of safety; a non-significant trend favoring DOACs in terms of efficacy is also evident.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Use of non-vitamin K oral anticoagulants (NOACs) has rapidly increased worldwide. We aimed to systematically assess the available evidence regarding the safety and efficacy of NOACs in patients undergoing cardiac implantable electronic device (CIED) surgery.. We performed a systematic literature search. Eligible randomised controlled trials and cohort studies were included. The primary outcome measures were clinically significant device-pocket haematoma and thromboembolic events.. Use of NOACs at the time of CIEDs surgery appears to be safe, and either strategy of peri-procedure continuation or interruption might be reasonable. However, continuation of NOAC seems to be associated with a numerically higher rate of bleeding complications. Certainty of the evidence is low, and further studies are required to confirm these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hematoma; Humans; Thromboembolism; Vitamin K

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with atrial fibrillation (AF) and peripheral artery disease (PAD) remain largely unknown. Therefore, we conducted a meta-analysis to explore the effects of NOACs versus warfarin in this population.. We systematically searched the PubMed and Embase databases, with no linguistic restrictions, until December 2019 for relevant randomized controlled trials (RCTs) and observational studies. A random-effects model using an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).. A total of six studies (three post hoc analyses of RCTs and three cohort studies) were included in this meta-analysis. Among AF patients treated with NOACs and warfarin, individuals with PAD had increased rates of all-cause death (RR = 1.26, 95% CI 1.07-1.48) and cardiovascular death (RR = 1.32, 95% CI 1.06-1.64) compared with those without PAD. In AF patients with PAD, we observed a similar risk of thromboembolic events, bleeding, and death with NOACs as with warfarin. In addition, there were no interactions between PAD and non-PAD subgroups regarding any of the reported outcomes of NOACs versus warfarin in AF patients (all P. Based on current evidence, AF patients with PAD are at a higher risk of death than those without PAD. Efficacy and safety outcomes with NOACs are comparable to those with warfarin, suggesting that the use of NOACs has effects similar to warfarin in AF patients with concomitant PAD.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Observational Studies as Topic; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Warfarin

This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in secondary stroke prevention in atrial fibrillation (AF) patients.. PubMed and Embase electronic databases were systematically searched from January 2009 to July 2019 for relevant randomized clinical trials and observational studies. A random-effects model was applied in the pooled analysis.. A total of 14 studies (4 randomized clinical trials and 10 observational studies) were included. Based on the randomized clinical trials, compared with VKA use, the use of NOACs was associated with decreased risk of stroke and systemic embolism, major bleeding, and intracranial bleeding. Based on the observational studies, compared with VKAs, the subgroup analysis showed that dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran and apixaban were associated with a decreased risk of major bleeding.. Based on current data, the use of NOACs is at least non-inferior to the use of VKAs in AF patients for secondary stroke prevention irrespective of NOAC type.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Observational Studies as Topic; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Secondary Prevention; Stroke; Thiazoles; Treatment Outcome; Vitamin K; Warfarin

In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF).. Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed.. During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95).. Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

Ischaemic stroke and systemic embolism are the major potentially preventable complications of atrial fibrillation (AF) leading to severe morbidity and mortality. Anticoagulation using vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOACs) is mandatory for stroke prevention in AF. Following approval of the four NOACs dabigatran, rivaroxaban, apixaban, and edoxaban, the use of VKA is declining steadily. Increasing age with thresholds of 65 and 75 years is a strong risk factor when determining annual stroke risk in AF patients. Current recommendations such as the "2016 Guidelines for the management of atrial fibrillation" of the European Society of Cardiology and the "2019 AHA/ACC/HRS Focused Update" by the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society strengthen the importance of anticoagulation and detection of bleeding risks, of which older age is an important one. While patients aged ≥ 75 years are usually underrepresented in randomised clinical trials, they represent almost 40% of the trial populations in the large NOAC approval studies. Therefore, a sufficient amount of data is available to assess the efficacy and safety for this patient cohort in that specific indication. In this article, the evidence for stroke prevention in AF using either VKA or NOACs is summarised with a special focus on efficacy compared to bleeding risk in patients aged ≥ 75 years. Specifically, we used a model of increased weighing of intracranial bleeding to illustrate the potential benefit of NOACs over VKA in the elderly population. In brief, there are at least two tested strategies with apixaban and edoxaban which even confer an additional clinical net benefit compared with VKA. Furthermore, elderly subgroups of trials for combined antithrombotic treatment following percutaneous coronary interventions in anticoagulated patients are analysed.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Vitamin K; Warfarin

Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019.. A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA.. A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A.. OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Consensus Development Conferences as Topic; Dabigatran; Europe; Female; Humans; Long-Term Care; Male; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Vitamin K; Warfarin

Vitamin K antagonist oral anticoagulants (VKAs) have been proven over 50 years to be highly effective and acceptably safe in many settings and are still used by millions of people worldwide. The main concern about the safety of VKAs regards the risk of bleeding, but there is accumulation evidence of their potentially negative effects beyond hemostasis. Indeed, VKAs impair the action of several Vitamin-K Dependent Proteins (VKDP), such as Bone Gla protein, Matrix Gla protein, Gas6 Protein, Periostin and Gla-Ric Protein, involved in bone and vascular metabolism, thus exerting a detrimental effect on bone and vascular health. Indeed, although the evidence regarding this issue is not compelling, it has been shown that VKAs use decreases bone mass density, increases the risk of bone fractures and accelerates the process of vascular and valvular calcification. Vascular calcification is a major concern in Chronic Kidney Disease (CKD) patients, also in absence of VKAs, because of mineral metabolism derangement, chronic inflammation and oxidative stress. Direct Oral AntiCoagulants (DOACs) do not affect VKDP involved in vascular and valvular calcification, and do not induce calcific valve degeneration in animal models, being a possible alternative to AVK for CKD patients. However, the efficacy and safety of DOACs in this population, suggested by some recent observations, requires confirmation by dedicated, randomized study. We reviewed here the effects of VKAs in bone and vascular health as compared to DOACs, in order to provide the physicians with some data useful to wisely choose the most suitable anticoagulant for every patient.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Vitamin K; Vitamins

Several studies have investigated the effectiveness and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and liver disease. Herein, we conducted a meta-analysis to compare the effect of NOACs with VKAs in patients with AF and liver disease. We also conducted a subsidiary analysis to compare the risk of liver injury between NOACs and VKA in AF patients. We systematically searched the PubMed and Embase databases from January 2009 to May 2020 for the relevant studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were selected and pooled using a random-effects model. A total of six cohorts were included. Compared with VKA use, the use of NOACs was associated with reduced risks of stroke or systemic embolism (HR 0.68, 95% CI 0.49-0.93), all-cause death (HR 0.69, 95% CI 0.63-0.75), and intracranial bleeding (HR 0.49, 95% CI 0.40-0.59), whereas the outcomes of major bleeding (HR 0.72, 95% CI 0.51-1.01) and gastrointestinal bleeding (HR 0.84, 95% CI 0.51-1.36) were not significantly different between groups in AF patients with liver disease. Moreover, compared with VKA use, the use of NOACs was associated with a reduced risk of liver injury (HR 0.72, 95% CI 0.61-0.84) in AF patients. Compared with VKAs, the use of NOACs was associated with reduced risks of stroke or systemic embolism, all-cause death, and intracranial bleeding in AF patients with liver disease, and associated with a reduced risk of liver injury in AF patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Administration Schedule; Humans; Liver Diseases; Stroke; Vitamin K

Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies.. In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing.. In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4-8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Factor Xa; Humans; Intracranial Hemorrhages; Recombinant Proteins; Risk Factors; Stroke; Vitamin K

Sex-specific differences have been definitively demonstrated in cardiovascular (CV) diseases. These differences can also impact on the effects of CV therapies. Female sex is recognized as an independent predictor of thromboembolic risk, particularly in older patients. Most of strokes are due to atrial fibrillation (AF). Women affected by AF have higher stroke risk compared to men. The introduction of novel oral anticoagulants (NOACs) for long-term anticoagulation completely changed the anticoagulant therapeutic approach and follow-up of patients affected by nonvalvular atrial fibrillation (NVAF). CHA2DS2-VASc stroke risk scoring in use in the current international guidelines attributes 1 point to "female sex". Besides, no anticoagulation is indicated for AF female patients without other risk factors. Interestingly, NOACs seem to normalize the differences between males and females both in terms of safety and efficacy, whereas residual higher stroke risk and systemic embolism persist in AF women treated with vitamin K antagonist anticoagulants VKA with optimal time in therapeutic range. Based on the CHA2DS2-VASc score, NOACs represent the preferred choice in NVAF patients. Moreover, complete evaluation of apparently lower risk factor along with concomitant clinical conditions in AF patients appears mandatory, particularly for female patients, in order to achieve the most appropriate anticoagulant treatment, either in male or in female patients. The present review was performed to review sex differences in AF-related thromboembolic risk reported in the literature and possibly highlight current knowledge gaps in prevention and management that need further research.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Clinical Decision-Making; Factor Xa Inhibitors; Female; Humans; Male; Patient Selection; Risk Assessment; Risk Factors; Sex Factors; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

Direct oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment.. Both observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vitamin K antagonists. A randomized trial of apixaban versus warfarin was terminated owing to poor enrollment and preliminary results identified no difference in clinical outcomes between groups. However, valuable pharmacodynamic data will be forthcoming from that trial. In observational research, among patients newly diagnosed with atrial fibrillation, there were opposing trends in the associations of apixaban initiation versus no oral anticoagulation with ischemic versus hemorrhagic stroke and no association was present with the overall risk of stroke or embolism. In another study comparing apixaban with warfarin initiation, apixaban was associated with less bleeding. Regular-dose apixaban (5 mg twice daily) associated with reduced rates of ischemic stroke or systemic embolism, whereas no such association was present for those prescribed the reduced dose (2.5 mg twice daily).. DOACs may be used after appropriate dose adjustment for an established clinical indication in patients with advanced CKD. Quality evidence for oral anticoagulation, with any specific agent or dose, for stroke prevention in hemodialysis continues to be lacking.

Topics: Acute Kidney Injury; Administration, Oral; Anticoagulants; Atrial Fibrillation; Glomerular Filtration Rate; Humans; Renal Insufficiency, Chronic; Stroke; Vitamin K

Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. However, the risk of bleeding and all-cause mortality in patients with edoxaban versus vitamin K antagonists (VKAs) is unclear.. We systematically searched all published studies of edoxaban versus VKAs. PubMed, CENTRAL databases and www.clinicaltrial.gov were searched for relevant articles published from January 1966 to 20 February 2020. All phase III randomized controlled trials (RCTs) comparing the risk of bleeding and all-cause mortality in patients with edoxaban versus VKAs were included in our meta-analysis. Both random- and fixed-effects models were used to pool data across phase III RCTs.. We included four trials that met our inclusion criteria (n = 33,077). They included patients with atrial fibrillation (3 trials, n = 24,847), venous thromboembolism (VTE) or pulmonary embolism (PE) (1 trial, n = 8240). Edoxaban was associated with reduced risks of major or clinically relevant nonmajor bleeding (CRNM) events (OR: 0.78, 95% CI: 0.68-0.89), any bleeding events (OR: 0.76, 95% CI: 0.72-0.80), and intracranial bleeding events (OR: 0.38, 95% CI: 0.29-0.48). They had a similar risk of gastro-intestinal bleeding (OR: 0.95, 95% CI: 0.79-1.13), death from any cause (OR: 0.97, 95% CI: 0.80-1.19), stroke (OR: 1.00, 95% CI: 0.88-1.14) and systemic embolic events (OR: 0.93, 95% CI: 0.57-1.51) between edoxaban and VKAs.. Compared to VKAs, edoxaban is safe as a direct oral anticoagulant, with respect to reduced risk of major or CRNM, intracranial bleeding events, and similar risk of gastro-intestinal bleeding events and all-cause mortality.

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Pyridines; Randomized Controlled Trials as Topic; Thiazoles; Vitamin K

Atrial fibrillation is a common cardiac disease of aging. The risk of stroke and bad prognosis increase with age and atrial fibrillation. Compared with younger people, elderly people have higher risks for both thrombosis and bleeding. Stroke prevention with oral anticoagulants is the cornerstone of the management of atrial fibrillation but is often questioned because of the risk of bleeding, furthermore comorbidities, comedications, fall risks, poor compliance. These factors frequently found in frail elderly patients complicate the management of antithrombotic therapy. This article reviews the evidence for the risks and benefits of anticoagulation in the elderly with atrial fibrillation, by comparing the new oral anticoagulants to vitamin K antagonists.. La fibrillation auriculaire est une pathologie cardiaque fréquente du vieillissement et l’accident vasculaire cérébral en est une complication reconnue et redoutable. L’anticoagulation préventive des événements thromboemboliques est souvent mise en doute chez le sujet âgé vulnérable ou dépendant en raison du risque hémorragique élevé lié aux caractéristiques de cette population : nombreuses comorbidités, risques de chute, faible compliance, polymédication. S’appuyant sur une revue de la littérature, cet article décrit les risques et les bénéfices de l’anticoagulation du sujet âgé souffrant d’une fibrillation auriculaire, en comparant les nouveaux anticoagulants oraux aux antagonistes de la vitamine K.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Risk Assessment; Risk Factors; Stroke; Vitamin K

There is still a paucity of data on the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) in the prevention of left atrial thrombus (LAT) formation before cardioversion or catheter ablation. To assess the efficacy of NOACs in the prevention of LAT in patients with non-valvular atrial fibrillation (NVAF) compared with vitamin K antagonists (VKAs), we conducted a meta-analysis.. We searched PubMed, Embase, and the Cochrane Library databases. For meta-analysis, dichotomous variables were analyzed by using the odds ratios (OR) computed using the Mantel Haenszel method (random models). All results were reported with 95% confidence intervals (CI).. A total of 13 studies (one randomized controlled investigation and 12 observational studies) were included in the meta-analysis. There was no statistically significant difference between the NOACs and VKAs groups with respect to the odds of LAT/LAAT formations (OR 0.79; 95% CI: 0.52-1.21; P = .29; (I2 = 14%).. NOACs were as effective as VKAs in the prevention of LAT/LAAT formation in patients with NVAF. Though patients on NOACs therapy showed a lower incidence of LAT/LAAT formation compared with VKAs, it was not significant (P = .29).

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Heart Atria; Heart Diseases; Humans; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Retrospective Studies; Vitamin K

Atrial fibrillation (AF) is the most common arrhythmia, ranging from 0.1% in patients <55 years to >9% in octogenarian patients. One important issue is represented by the 5-fold increased ischemic stroke risk in AF patients. Hence, the role of anticoagulation is central. Until a few years ago, vitamin K antagonists (VKAs) and low molecular weight heparin represented the only option to prevent thromboembolisms, though with risks. Novel oral anticoagulants (NOACs) have radically changed the management of AF patients, improving both life expectancy and life quality. This review aims to summarize the most recent literature on the use of VKAs and NOACs in AF, in light of the new findings.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Humans; Risk Factors; Stroke; Vitamin K

Non-vitamin K-dependent oral anticoagulants (NOAC) have changed the management of patients with oral anticoagulation. This raises the question of which patients should preferably be anticoagulated with NOAC and which preferably with vitamin K antagonists (VKA). This discussion has so far been insufficiently conducted and often decided on a flat-rate basis in favor of the NOAC.. To clarify the question owhich form of anticoagulation - NOAC or VKA - is the best choice for patients with atrial fibrillation, an interdisciplinary team of experts met.. The experts discussed essential practical aspects of NOAC and VKA therapy. Based on typical clinical scenarios, they developed assistance, comments and tips on the differentiated use of oral anticoagulants in patients with atrial fibrillation. A criteria served amongst others practicability in daily medical practice, contraindications, side effects and interactions, but also the patient's desire. The advantages and disadvantages of therapy with VKA and NOAC were summarized in a table.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Physical Therapy Modalities; Vitamin K

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have several advantages over VKAs that render them an attractive option for adults with congenital heart disease (CHD). Efficacy and safety data specific to the adult CHD population are emerging. Herein, we synthesize the growing literature regarding NOACs in adults with CHD and attempt to identify subgroups for which it appears reasonable to extrapolate data from populations without CHD. Small observational studies suggest that NOACs are safe and effective in selected adults with CHD. NOACs are contraindicated in patients with a mechanical valve, in those with mitral or tricuspid valve stenosis with enlarged and diseased atria, with or without a mitral or tricuspid bioprosthesis, and after recent cardiac surgery (< 3 months). There is currently insufficient evidence to recommend NOACs in patients with a Fontan circulation or cyanotic CHD. Growing literature supports the use of NOACs in patients without CHD who have various forms of valvular heart disease. Therefore, when an indication for oral anticoagulation is established, it appears reasonable to consider a NOAC instead of a VKA in adults with CHD lesions analogous to isolated mitral regurgitation, tricuspid regurgitation, or aortic regurgitation or stenosis. The NOAC agent selected and the prescribed dose should be tailored according to bleeding risk, body weight, renal function, and comedications, especially antiepileptic drugs. The decision to initiate a NOAC should be shared between the patient and care provider. Large-scale research studies are required to further assess safety and efficacy in selected patient subgroups.

Topics: Administration, Oral; Adult; Age Factors; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Dabigatran; Female; Heart Defects, Congenital; Heart Valve Diseases; Humans; Male; Prognosis; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Severity of Illness Index; Sex Factors; Stroke; Survival Analysis; Thiazoles; Vitamin K

This study assessed the incremental benefit of uninterrupted direct oral anticoagulants (DOACs) versus uninterrupted vitamin K antagonists (VKAs) for catheter ablation (CA) of nonvalvular atrial fibrillation (NVAF) on 3 primary outcomes: major bleeding events (MBEs), minor bleeding events, and thromboembolic events (TEs). The secondary outcome was post-procedural silent cerebral infarction (SCI) as detected by brain cardiac magnetic resonance.. As a class, evidence of the benefits of DOACs versus VKAs during CA of AF is scant.. A systematic review of Medline, Cochrane, and Embase was done to find all randomized controlled trials in which uninterrupted DOACs were compared against uninterrupted VKAs for CA of NVAF. A fixed-effect model was used, except when I. The benefit of uninterrupted DOACs over VKAs was analyzed from 6 randomized control trials that enrolled a total of 2,256 patients (male: 72.7%) with NVAF, finding significant benefit in MBEs (relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.20 to 0.99; p = 0.05). No significant differences were found in minor bleeding events (RR: 1.12; 95% CI: 0.87 to 1.43; p = 0.39), TEs (RR: 0.75; 95% CI: 0.26 to 2.14; p = 0.59), or post-procedural SCI (RR: 1.09; 95% CI: 0.80 to 1.49; p = 0.58).. An uninterrupted DOACs strategy for CA of AF appears to be safer than uninterrupted VKAs with a decreased rate of major bleeding events. There are no significant differences among the other outcomes. DOACs should be offered as a first-line therapy to patients undergoing CA of AF, due to their lower risk of major bleeding events, ease of use, and fewer interactions.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Hemorrhage; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Vitamin K

The 2016 European Society of Cardiology Guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) in preference to vitamin K antagonists (VKA) for stroke prevention in atrial fibrillation. A recent report from the Belgian Healthcare Knowledge Centre (KCE) raised concerns about the results of the phase 3 randomised trials that led to the approval of the NOACs for this indication and concluded that NOACs should only be used for patients who fail or cannot undergo treatment with a vitamin K antagonist because they cannot achieve stable INR values. Evidence from community-based studies suggests that NOACs are often not optimally used; however, our critical review of the randomised trial data provides no support for the concerns raised by the Belgian KCE about the trials. Furthermore, the results of observational studies involving more than 700,000 participants replicate those of the randomised trials, indicating that the benefits of NOACs seen in the trials can be readily translated to patient care. Due to their superior convenience and safety, NOACs also have the potential to reduce undertreatment of atrial fibrillation patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Belgium; Cardiology; Humans; Practice Guidelines as Topic; Societies, Medical; Stroke; Vitamin K

To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation.. A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA statement. The ROBINS-I tool was used to assess risk of bias.. A total of 27 different studies publishing data in 30 publications were included. In the studies with a follow-up up to 1 year, apixaban (HR, 0.93; 95%CI, 0.71-1.20) and dabigatran (HR, 0.95; 95%CI, 0.80-1.13) did not significantly reduce the risk of ischemic stroke vs warfarin, whereas rivaroxaban significantly reduced this risk (HR, 0.83; 95%CI, 0.73-0.94). Apixaban (HR, 0.66; 95%CI, 0.55-0.80) and dabigatran (HR, 0.83; 95%CI, 0.70-0.97) significantly reduced the major bleeding risk vs warfarin, but not rivaroxaban (HR, 1.02; 95%CI, 0.95-1.10), although with a high statistical heterogeneity among studies. Apixaban (HR, 0.56; 95%CI, 0.42-0.73), dabigatran (HR, 0.45; 95%CI, 0.39-0.51), and rivaroxaban (HR, 0.66; 95%CI, 0.49-0.88) significantly reduced the risk of intracranial bleeding vs warfarin. Reduced doses of direct oral anticoagulants were associated with a slightly better safety profile, but with a marked reduction in stroke prevention effectiveness.. Data from this meta-analysis suggest that, vs warfarin, the stroke prevention effectiveness and bleeding risk of direct oral anticoagulants may differ in real-life patients with atrial fibrillation.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Dabigatran; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Observational Studies as Topic; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K; Warfarin

Non-vitamin K oral anticoagulants (NOACs) have consistently demonstrated superior efficacy in terms of stroke prevention and safety in terms of bleeding over vitamin K antagonist (VKA) in patients with non-valvular atrial fibrillation (AF). The potential use of NOACs in AF patients requiring antiplatelet therapy (APT) has only been assessed in small meta-analyses reporting consistent benefits of NOACs over VKAs. However, the prescription costs of NOACs are higher than those of VKAs. The aim of his study was to estimate the cost-effectiveness (CE) of NOACs compared to VKAs in patients with non-valvular AF also requiring APT with the Dutch healthcare system used as a surrogate of many European healthcare systems.. A decision tree was constructed to analyse the CE of NOACs compared to VKAs in patients with non-valvular AF with an indication for APT over a horizon of 1 year. Beside the base-case analysis, univariate probabilistic sensitivity and two sensitivity analyses were performed: first, we assessed the impact of VKA home monitoring; second, we varied the NOACs price assuming patent expiration. Use of NOACs instead of VKA is associated with a health gain of 0.0171 quality-adjusted life years (QALYs) and with an incremental cost of €357, resulting in an incremental cost-effectiveness ratio of €20 919, which is almost equal to the generally accepted CE threshold of €20 000 used in the Netherlands. The probability that NOACs are cost-effective at a conservative willingness-to-pay threshold of €20 000 per QALY was 50%. Introducing home monitoring increased VKAs costs so much that NOACs became the dominant option (less costly and more effective). Price drops associated to patent expiration of NOACs increased its CE.. This analysis suggests that the use of NOACs is a cost-effective alternative of VKAs in patients with AF needing APT. Our findings in the Netherlands healthcare system are probably consistent with other European populations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Humans; Netherlands; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Stroke; Vitamin K

Atrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Neoplasms; Risk Factors; Stroke; Thromboembolism; Vitamin K

In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice.. By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies.. For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions.. DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Network Meta-Analysis; Stroke; Vitamin K

Catheter ablation has been established as a rhythm control strategy in selected patients with atrial fibrillation (AF) who have failed or wish to avoid anti-arrhythmic drugs. Uninterrupted oral anticoagulation with vitamin K antagonists (VKAs) peri-ablation is associated with a lower risk of thromboembolic and bleeding complications as compared to interrupted oral anticoagulation and bridging heparin. However, a substantial portion of patients with AF are treated with non-vitamin K antagonist oral anticoagulants (NOACs). Herein, we perform an in-depth review and comparison of three recent randomized trials of uninterrupted oral anticoagulation with NOACs vs VKAs in patients undergoing AF catheter ablation. Furthermore, we report pooled results of these randomized trials. The pooled incidence of major bleeding was significantly lower with NOACs as compared to VKAs (2% vs 4.9%, respectively; odds ratio [OR] 0.40; 95% confidence intervals [CI] 0.16-0.99). Similarly, cardiac tamponade was also reduced in the NOAC group (0.4% vs 1.5%; OR 0.27; 95% CI 0.07-0.97). Thromboembolic complications were not significantly different between groups. Overall, these findings support the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement's class I recommendation for uninterrupted NOAC use in patients undergoing AF catheter ablation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Randomized Controlled Trials as Topic; Thromboembolism; Vitamin K

Vitamin-K antagonists (VKA) have been the standard for oral anticoagulation. However, they carry several problems in older patients: frequent bleeding complications, complex management, risk of interactions with multiple drugs. Two classes of direct oral anticoagulants (DOA) are currently available in France: (a) direct thrombin inhibitors: dabigatran; and (b) direct factor Xa inhibitors: rivaroxaban, apixaban and others. Their management is easier: quickly effective after administration, they are given at fixed doses and do not need regular laboratory monitoring. Several randomized trials have shown that DOA are non-inferior to VKA for treating venous thromboembolic disease (prophylactic or curative treatment) and atrial fibrillation (prevention of associated embolisms). DOA might be also effective for long-term treatment of coronary disease, in some cases. No trial has specifically studied older patients. In the context of atrial fibrillation, subgroup analysis show similar results between patients above and below 75-years-old. Lower doses of dabigatran and apixaban should be used in many older people. All DOA are eliminated at least partly by kidneys. Their dose must be reduced in moderate renal failure (filtration glomerular rate (FGR) 30 to 50mL/min) and they are contraindicated in older patients with severe renal failure (FGR<30mL/min). DOA also have other problems: (a) important drug interactions are still possible, (b) the clinical application of specific coagulation tests need to be defined, (c) their safety in some subgroups of elderly patients, very different from patients included in clinical trials, is not known.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Contraindications, Drug; Dose-Response Relationship, Drug; Drug Interactions; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemorrhage; Humans; Renal Insufficiency, Chronic; Risk Factors; Secondary Prevention; Stroke; Thromboembolism; Vitamin K; Warfarin

As overall prevalence of atrial fibrillation (AF) continues to rise, the number of patients who undergo ablation, or electrical/chemical cardioversion, to restore normal sinus rhythm continues to increase as well. As direct oral anticoagulants (DOACs) have continued to be incorporated into clinical practice for long-term anticoagulation for AF, experience with how best to manage use of DOACs during electrophysiologic procedures is evolving. This review is intended to provide health care providers with a summary of current evidence regarding the use of DOACs during cardioversion and catheter ablation and provide key considerations for their use during such electrophysiologic procedures. PubMed and MEDLINE were searched from inception through June 2018 for studies in humans comparing DOACs alone or against vitamin K antagonists (VKAs) in adult patients (> 18 yrs) who underwent cardioversion or AF catheter ablation using the following key words: "rivaroxaban," "dabigatran," "apixaban," "edoxaban," "non-vitamin K antagonists," "direct or new oral anticoagulants," "warfarin," "vitamin K antagonists," "cardioversion," "ablation of atrial fibrillation," "uninterrupted," and "catheter ablation." Four retrospective studies and three prospective trials comparing DOACs with VKA in patients undergoing cardioversion and three prospective studies in patients undergoing catheter ablation for AF were identified. Observational data and meta-analyses were also critically reviewed. Prospective trials to date suggest similar efficacy and safety with using DOACs in the setting of cardioversion and AF ablation compared to traditional therapy with VKA, with or without bridging. Injectable anticoagulant overlap can be avoided in patients receiving DOACs in the setting of cardioversion for AF. Minimal interruption in anticoagulation may be only necessary for AF ablation in those with highest bleeding risk, such as in renal dysfunction and where drug-drug interactions may increase risk for anticoagulant accumulation. Periprocedural advantages of DOACs include convenience, rapid and predictable onset of effect, improved patient satisfaction, and potential for reduced costs.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Electric Countershock; Humans; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit-risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug-drug interactions and preference for once- or twice-daily dosing. In addition, several 'special situations' were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Atrial Fibrillation; Benzamides; Biomarkers; Blood Coagulation; Clinical Trials as Topic; Dabigatran; Drug Administration Schedule; Factor Xa; Heart Diseases; Humans; Piperazines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Risk; Rivaroxaban; Stroke; Thiazoles; Thrombin; Venous Thromboembolism; Vitamin K; Warfarin

For procedures associated with minimal bleeding risk, there are data and experience to support the practice of continuing vitamin K antagonists rather than interrupting therapy, to prevent exposing patients to the undue risk of developing thromboembolism during anticoagulation cessation. Despite the increasing use of non-vitamin K oral anticoagulants (NOACs), there is little evidence to guide the management of these drugs around minimal bleeding risk procedures. This review examines and discusses the major society guidelines and recommendations addressing the management of NOACs around minimal bleeding risk procedures. Additionally, it summarizes the existing evidence, and highlights the gaps in knowledge where evidence is not yet available. Finally, recommendations are made to assist the proceduralist deal with this area of limited evidence.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Practice Guidelines as Topic; Risk Factors; Venous Thromboembolism; Vitamin K

The direct oral anticoagulants (DOACs) have emerged as an effective and safe alternative to vitamin K antagonists (VKAs) for stroke and venous thromboembolism (VTE) prevention. However, patients with chronic kidney disease (CKD) experience an increase in the risk of both thromboembolism and bleeding, and the risk-benefit profile of DOACs, particularly in advanced CKD remains a source of ongoing debate. This review summarizes the recent evidence on the effects of DOACs in CKD across a range of clinical indications including newly emerging indications.. Data on early-to-moderate stage CKD derived from pivotal randomized controlled trials in broader atrial fibrillation and VTE populations support the favorable risk-benefit ratio of DOACs compared with VKAs in patients in these groups. However, safety data from observational studies comparing DOACs with VKAs in patients with atrial fibrillation and CKD (moderate to advanced) have been conflicting. Recent trials have evaluated the efficacy of low-dose DOACs on major cardiovascular outcomes, showing promising risk-benefit ratios in high-risk populations with concurrent CKD.. Current data on patients with CKD derived from trials in the broader population suggest that DOACs are an effective alternative to VKAs in patients with early-to-moderate stage CKD. However, studies on patients with advanced CKD are lacking. Further randomized controlled trials, particularly those evaluating the risk of any clinically relevant bleeding as part of a more accurate assessment of the risk-benefit profile of DOACs in people with CKD, are needed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Stroke; Venous Thromboembolism; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) have proven a favorable risk-benefit profile compared to vitamin K antagonists (VKAs) for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but actual data are not sufficiently powered to extend this profile on patients with AF that undergo cardioversion. We aimed to compare outcomes after cardioversion of AF under NOACs vs. VKAs. We systematically searched Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies published until October 2017. A total of 17506 patients from 11 studies were included. Treatment with NOACs was associated with similar relative risks (RR) of stroke and systemic embolism, hemorrhagic stroke, myocardial infarction, cardiovascular death, and all cause death compared to VKAs treatment. The RR of ischemic stroke was lower in the NOACs group. The risk of major bleeding was similar across treatment groups. Treatment with NOACs in patients with non-valvular AF that undergo cardioversion seems to be as safe and effective as the use of classical VKAs, with a better profile for ischemic stroke. Clinical Trial Registration: PROSPERO Registry, CRD42018086181 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 86181 .

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Embolism; Humans; Myocardial Infarction; Stroke; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOAC) are equally or potentially superior in terms of effectiveness in the prevention of ischemic stroke and carry a lower associated risk of intracranial hemorrhage compared to Vitamin K antagonists. Nevertheless, ischemic strokes also occur in patients who are being treated with NOAC. In those particular patients, knowledge about the underlying stroke etiology, clinical presentation, acute management, and complication rates is scarce.. Systematic literature review to provide a comprehensive clinical overview in terms of presentation, laboratory, imaging parameters and outcomes of patients suffering from acute cerebral ischemic events (i.e. TIA and acute ischemic stroke) while on treatment with a NOAC. Only if available, comparison to VKA is presented which was not the primary focus of this analysis.. PubMed/MEDLINE, Scopus and EMBASE from January 1, 2006, to November 20, 2018.. 52 studies providing detailed information on a total of 12247 patients were included. We excluded case reports and case series with less than five patients.. We systematically assessed study quality using a bias tool and pooled consistent data.. Existing data indicates milder stroke severity and smaller infarct size of acute ischemic stroke on treatment with NOAC compared to stroke occurrence on Vitamin K antagonists (VKA). Established risk factors for ischemic events also play a role in stroke while on NOACs, albeit the underlying etiology remains poorly understood. Intravenous thrombolysis and endovascular therapy seem to be safe and effective, but patient selection for recanalization therapies is challenging.. Limited quality of published data, duplicate cases, statistical issues of data pooling, possible incomplete retrieval of identified research and reporting bias might have limited our findings.. Acute ischemic events despite treatment with NOAC therapy are insufficiently investigated.. PROSPERO: CRD42018074853.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Endovascular Procedures; Female; Humans; Ischemic Attack, Transient; Male; Reperfusion; Risk Factors; Stroke; Thrombolytic Therapy; Vitamin K

The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also necessitated a good understanding of the pharmacological properties of each of these drugs prior to their use, to maximise the therapeutic benefit and minimise patient harm Areas covered: This review article outlines the pharmacokinetic and pharmacodynamic profiles of the currently licensed VKAs and NOACs that are most commonly used in clinical practice, with the aim of demonstrating how variations in these characteristics influence their use in clinical practice. A literature search was conducted on PubMed using keywords and relevant articles published by the 31

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Humans; Membrane Transport Proteins; Pharmacogenetics; Vitamin K

BACKGROUND Oral anticoagulants (OACs) such as warfarin and non-VKA oral anticoagulants (NOACs) have been recommended for patients with atrial fibrillation (AF) who are at risk for stroke. Whether NOACs have a higher persistence than warfarin is still unclear. This is especially true in China. MATERIAL AND METHODS Data from a large hospital-based cohort in China (China-AF Registry) from 2011 to 2017 were used for this study. Non-valvular AF patients with newly initiated OACs were included. A time-to-event approach was used to analyze patient persistence. The survival distributions of persistence were compared using the log-rank test. A multivariable Cox regression model was used to explore predictors of warfarin and NOACs non-persistence. RESULTS Patients with newly initiated warfarin (n=4845) or NOACs (n=854) were included in this study. Persistence rates at 1, 2, and 3 years were 93.2%, 89.4%, and 87.2% in the warfarin group and 88.8%, 84.3%, and 81.3% in the NOAC group respectively. Non-persistence was significantly higher with NOACs than with warfarin. On multivariate analysis, age <75 years old, outpatient clinic visits, asymptomatic AF, paroxysmal AF, duration of AF <3 years, history of peptic ulcer, and no previous TIA, stroke or thromboembolism were strong predictors of warfarin non-persistence, while in the NOACs group, age <75 years old, outpatient clinic visits, lower education status and no history of congestive heart failure were predictors. CONCLUSIONS Treatment persistence of NOACs was lower than that of warfarin among Chinese patients with AF. Patients with characteristics of non-persistence predictors need special attention to maintain their therapy.

Topics: Aged; Anticoagulants; Atrial Fibrillation; China; Female; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Prospective Studies; Registries; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Clinical guidelines recommend peri-cardioversion anticoagulation in patients with atrial fibrillation (AF). We performed a systematic review and meta-analysis to compare the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with AF undergoing cardioversion.. We searched CENTRAL, MEDLINE, and EMBASE for randomized controlled trials (RCTs) and observational studies comparing DOACs to VKAs in patients undergoing cardioversion for AF. We performed title, abstract, and full-text screening, data extraction, and risk of bias evaluation independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence using Grading of Recommendations Assessment, Development and Evaluation.. We identified three eligible RCTs (n = 5203) and 21 observational studies (n = 11,855). The three RCTs and four observational studies were at low risk of bias. In RCTs (mean follow-up, 30 days), thromboembolic events occurred in 0.18% of patients receiving DOACs, as compared with 0.55% receiving VKAs (relative risk [RR] 0.40, 95% CI [0.13, 1.24], moderate quality). Major bleeding occurred in 0.42% of patients receiving DOACs as compared with 0.64% receiving VKAs (RR 0.62, 95% CI [0.28, 1.35], moderate quality), and death occurred in 0.28% of patients receiving DOACs as compared with 0.38% receiving VKAs (RR 0.70, 95% CI [0.23, 2.10], low quality). Confidence in the estimates of effect for observational studies was very low.. DOACs peri-cardioversion in patients with AF appears safe from both a bleeding and thromboembolic risk perspective. Available evidence supports the use of DOACs as standard of care peri-cardioversion in patients with AF.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Electric Countershock; Hemorrhage; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Vitamin K antagonists (VKAs) cannot be administered without regular monitoring in order to assure their efficacy and safety. Indeed, if well managed, the VKAs appear to be no less efficacious or safe than the newer direct oral anticoagulants (DOACs). Although it is claimed that no regular monitoring of the DOACs is needed, their levels are increasingly being measured under a variety of circumstances, for example, prior to surgery, in suspected overdose, to confirm effective reversal, in patients with malabsorption and to assess patient compliance. Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases. Furthermore, it has been determined that almost all dabigatran-related thrombotic events occur in patients with the lowest quartile concentration of the drug. This suggests that to assure an ideal effect of DOACs in all patients taking them, some form of regular monitoring and dose tailoring should be performed. For the vitamin K antagonists, the best outcome is obtained using formal algorithms and centralized management. Furthermore, data suggest that replacing the standard prothrombin time as a monitoring test may increase the stability of VKA anticoagulation with consequent reduction in thromboembolism without an increase in bleeding. Thus, it is likely that the outcome of all current oral anticoagulants can be improved in the coming years by improving monitoring and tailoring their effect.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Monitoring; Hemorrhage; Humans; Venous Thromboembolism; Vitamin K

Antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remain challenging. This study aims to explore the best antithrombotic strategy for AF patients after PCI based on a network meta-analysis. This study was registered in PROSPERO (CRD42018093928). The PubMed, Cochrane, and EMBASE databases were searched to identify clinical trials concerning antithrombotic therapy for AF patients with PCI from inception to April 2018. Pairwise and network meta-analysis were conducted to compare clinical outcomes of different antithrombotic therapy. The primary endpoint was major bleeding. Fifteen studies including 16,382 patients were identified with follow-up ranging from 3 to 12 months. Non-vitamin K oral anticoagulants (NOAC) plus P2Y

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Observational Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Vitamin K

Topics: Administration, Oral; Algorithms; Animals; Anticoagulants; Atrial Fibrillation; Humans; Pharmacogenetics; Polymorphism, Genetic; Stroke; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Vitamin K

The direct-acting oral anticoagulants (DOACs) are drugs that have been shown to have a safety profile superior to the vitaminK antagonists (VKA). The prescribing of DOACs in Spain is subject to approval in the form of an inspection visa. This sets out the clinical conditions defined in the Spanish Medicines Agency Therapeutic Positioning Report (TPR) of 2013, updated in 2016. These recommendations do not coincide with those of the European Cardiology Society (2016), restricting the use of DOACs to a second-line treatment in the majority of cases. Furthermore, this TPR is applied differently in the Regional Autonomous Communities and even in different health areas. This leads to a wide variation in the prescribing conditions, causing territorial inequalities in accessibility to these drugs by patients. The removal of the visa, and the appropriateness of the prescription to the recommendations of the Clinical Practice guidelines are key aspects to neutralise the current administrative and clinical barriers for the efficient use of DOACs in Primary Care. SEMERGEN supports the boosting of the clinical training and alliance with the patients in order to promote awareness and knowledge of atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Practice Guidelines as Topic; Primary Health Care; Spain; Vitamin K

This review summarizes the available evidence concerning direct oral anticoagulant (DOAC) use to treat venous thromboembolism (VTE) in patients with cancer as well as pertinent safety data on the use of DOACs in patients with both cancer and atrial fibrillation.. The introduction of DOACs into clinical practice changed the way thrombotic complications are managed and prevented in diverse patient populations, including VTE and atrial fibrillation. Low-molecular-weight heparins have been the standard of care for treating VTE in cancer patients due to superiority over vitamin K antagonists in preventing recurrent VTE. Therefore, widespread DOAC use for VTE in patients with active cancer has not been adopted.. Recent randomized clinical trials (SELECT-D, Hokusai VTE Cancer) have provided evidence that DOACs may have a role in treating VTE in cancer patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Standard of Care; Treatment Outcome; Venous Thromboembolism; Vitamin K

Vitamin K antagonists (VKA) are used for the prophylaxis and treatment of thrombotic and thromboembolic events. Most important indications are venous thrombosis and pulmonary embolism, atrial fibrillation, and mechanical heart-valve replacement. Hence they are from high relevance for the neurologist and his daily praxis in cardio-neurological routine. Here, we give an overview about VKA with focus on mode of action, indications and efficacy, practical aspects of treatment, side effects, and monitoring.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coumarins; Humans; Thromboembolism; Vitamin K

Catheter ablation is recommended as a first- or second-line rhythm control therapy for selected patients with atrial fibrillation (AF). There is a wide variability in the periprocedural management of oral anticoagulation in patients undergoing AF ablation.. We aimed to perform an updated meta-analysis of novel oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) as uninterrupted anticoagulation in patients undergoing AF ablation.. Databases and conference abstracts were searched. Studies were excluded if oral anticoagulants were held at any periprocedural period. The primary outcomes were stroke or transient ischemic attack (TIA) and major bleeding.. Twelve studies and 4962 patients were included. Stroke or TIA was rare (NOAC, 0.08%; VKA, 0.16%) and not different between groups (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.19-2.30). The incidence of silent cerebral embolic events was also not significantly different between NOACs (8%) and VKAs (9.6%) (OR 0.86; 95% CI 0.42-1.76). Major bleeding was significantly reduced in the NOAC group (0.9%) as compared with VKA-treated patients (2%) (OR 0.50; 95% CI 0.30-0.84; P < .01). This finding was confirmed in a subgroup analysis of randomized and cohort studies with matched controls (OR 0.45; 95% CI 0.24-0.83; P = .01). There was no significant difference in the outcomes of individual NOACs and VKAs, although these analyses may have been underpowered to detect minor differences in such rare outcomes.. In patients undergoing AF ablation, uninterrupted periprocedural NOACs are associated with a low incidence of stroke or TIA and a significant reduction in major bleeding as compared with uninterrupted VKAs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Stroke; Vitamin K

The non-vitamin K antagonist oral anticoagulants (NOACs) were approved for non-valvular atrial fibrillation (AF) but this term may be misnomer. Thus, the term non-mechanical and rheumatic mitral valvular (non-MARM) AF was proposed to exclude patients with valvular heart disease (VHD) without contraindications for NOACs. We aimed to review the efficacy and safety of NOACs in patients with AF and VHD compared to Vitamin K Antagonists (VKA). We performed a systematic review with meta-analysis (PROSPERO CRD42015024837) including data from randomized controlled trials (RCTs) retrieved in November 2016. The efficacy and safety data were pooled using random-effects meta-analyses using the hazard ratio (HR) with the 95% confidence interval (95%CI). Trial sequential analysis (TSA) was performed in statistical significant results to evaluate whether cumulative sample size was powered for the obtained effect. In 5 RCTs (with 12 653 VHD AF patients), NOACs significantly reduced the risk of stroke and systemic embolism (HR 0.73, 95%CI:0.60-0.90; TSA showed estimate was robust - O'Brien-Fleming α-spending boundary crossed before reaching the estimated information size) and intracranial hemorrhage (HR 0.45, 95%CI:0.24-0.87) compared with VKA. Major bleeding risk was not significantly different. In patients with bioprosthesis (3 trials-280 patients) the risks of thromboembolism (HR 0.65, 95%CI:0.20-2.08) and major bleeding (HR 0.94, 95%CI:0.28-3.18) with NOACs were similar to VKA. NOACs are efficacious and safe in patients with non-MARM VHD AF, showing significant reduction in the risk of stroke and systemic embolism and intracranial hemorrage compared with VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Humans; Risk Factors; Thromboembolism; Vitamin K

Prevention of stroke is a pivotal intervention in the management of patients with atrial fibrillation (AF). Because of the difficulties of safely implementing Vitamin K Antagonists in all patients, there has been a growing interest in improving the pharmacological management of AF with newer antithrombotic agents. The new oral anticoagulants (NOACs) have been developed to overcome the limitations and improve the efficacy of the conventional oral anticoagulant drugs. Among the NOACs, apixaban - a very specific antagonist of activated factor Xa - has pharmacokinetic and pharmacodynamic properties that allow significant efficacy in AF management.. The aim of this review is to summarise the available data on the efficacy of apixaban in patients with AF, with a particular focus on the implications for its clinical management.. Clinical application of apixaban in subgroups of patients with AF is still under investigation and some contraindications should be taken into account. Despite these limitations, apixaban is an effective alternative to warfarin and aspirin for stroke prevention in AF, with encouraging evidence also in terms of adherence to treatment.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Stroke; Vitamin K

Atrial fibrillation (AF) is the most frequently encountered sustained arrhythmia with a prevalence of 0.5-10%, depending predominantly on age. The arrhythmia is associated with significant morbidity and mortality, mainly due to thromboembolic events including stroke and systemic embolisms. These complications can be effectively prevented with anticoagulation therapy either with vitamin K antagonists (VKA) or with non-vitamin K antagonists (NOAC). VKA therapy is effective in preventing strokes but these medications are difficult to use, are associated with significant bleeding risk, and have pharmacokinetic/dynamic properties that make their use cumbersome. NOACs-either factor II or factor Xa inhibitors-have been developed over the past two decades and have been tested against VKA in large randomized controlled trials. This trial evidence was complemented more recently by increasing real-world data comprising several 100,000 patients. Finally, NOACs have been examined for their use in specific clinical situations, for example, in patients undergoing cardioversion, catheter ablation, or coronary interventions. In all of these clinical scenarios, NOACs have been similarly effective or-in many instances-even superior to treatment with VKA. Recent guidelines, therefore, recommend NOAC therapy for stroke prevention in AF as first-line therapy.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Platelet Aggregation Inhibitors; Prothrombin; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Stents; Thromboembolism; Venous Thrombosis; Vitamin K

The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation.. We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs.. From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (. Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Female; Humans; Intracranial Hemorrhages; Male; Polymers; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Saliva, Artificial; Stroke; Vitamin K; Warfarin

Identifying patients who are likely to achieve and maintain a therapeutic international normalized ratio when prescribed a vitamin K antagonist for stroke prevention in atrial fibrillation (AF) and venous thromboembolism (VTE) is challenging. The SAMe-TT

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Clinical Decision-Making; Humans; Venous Thromboembolism; Vitamin K

This observational study aimed to investigate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with malignancy. A total of 76 patients (mean age: 73.2 ± 8.9; 28 females) with AF and malignancy treated with NOAC were included in the analysis. The mean CHA

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Retrospective Studies; Vitamin K

Patients with end-stage renal disease (ESRD) were excluded from pivotal clinical trials with oral anticoagulants. While such patients are at an increased risk of venous and arterial thromboembolism, their risk of bleeding is also elevated. It is thus of little surprise that stroke prevention with vitamin K antagonists (VKAs) in ESRD patients with atrial fibrillation is controversial, with observational evidence ranging from beneficial to harmful. This uncertainty extends to the less studied use of VKAs for venous thromboembolism in ESRD. The direct oral anticoagulants (DOACs) apixaban and rivaroxaban have now permissive labeling in the United States for atrial fibrillation in patients with ESRD; this expanded labeling has not yet occurred either in Europe or for venous thromboembolism. This review summarizes the current evidence for the pharmacology of DOACs in ESRD as well as their utilization and safety in patients with ESRD and atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Rivaroxaban; United States; Venous Thromboembolism; Vitamin K

Atrial fibrillation (AF) is a leading cause of stroke. Oral anticoagulant (OAC) therapy can significantly reduce the risk of stroke in patients with AF, but underuse of OACs for stroke prevention continues to be a serious clinical problem, with significant deleterious impact on outcomes. We review the studies demonstrating OAC underutilization and evaluating strategies for promoting the increased use of OAC therapy for stroke prevention in nonvalvular AF (NVAF) patients, including in special patient populations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Prescriptions; Health Services Misuse; Humans; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Pharmacological or electrical cardioversion allows immediate symptoms improvement in the setting of paroxysmal or persistent atrial fibrillation (AF), although the periprocedural risk of systemic embolism should be considered. Recently, there was a great interest on the safety and efficacy of direct oral anticoagulants (DOACs) when used for the cardioversion of non-valvular AF. We performed a random-effects meta-analysis of patients undergoing both electrical and pharmacologic cardioversion for non-valvular AF in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, X-VeRT, ENSURE-AF, and EMANATE trials. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for stroke/systemic embolism (SSE) and major bleeding (MB) at follow-up. A total of 8564 patients have been included in the analysis. When compared with patients receiving vitamin-K antagonists (VKAs), patients receiving DOACs had a lower risk of SSE (RR 0.70, 95% CI 0.33-1.546, P = 0.34), as well as of MB (RR 0.86;,95% CI 0.47-1.58, P = 0.62), although both were non-significant. Funnel plot analysis showed, however, lower RRs with more recent ad hoc studies in comparison with registrational studies, even though statistical significance was not reached. DOACs are as effective and as safe as VKAs for thromboembolic prevention in non-valvular AF in the setting of cardioversion. There are differences, although non-significant, between registrational studies and studies enrolling exclusively patients undergoing cardioversion of AF.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Hemorrhage; Humans; Odds Ratio; Thromboembolism; Vitamin K

Atrial fibrillation is a frequent reason for presentation to an emergency department (ED), and the number of these visits are increasing. This creates an opportunity to improve the suboptimal rate of oral anticoagulation (OAC) use in patients with atrial fibrillation who are at high risk of stroke. However, there are very few data on whether OAC initiation in the ED, compared with referral to the longitudinal health care provider to initiate it, results in better long-term use. Moreover, for ethical and medicolegal reasons, physicians who initiate a chronic medication are obliged to reassess the patient at a later date, to check for medication side effects and the need for dose adjustment. More research is needed to determine whether OAC should be prescribed in the ED, by a physician who will never see the patient again. Patients who are cardioverted in the ED might be an exception, secondary to the increased risk of stroke after cardioversion. If ED OAC prescribing is associated with better outcomes, these results must be placed into context with the care and outcomes of the other patients in the ED. If there is a net benefit, the findings should be disseminated to practicing emergency physicians, preferably via emergency physician opinion leaders. An implementation science-based approach, which addresses the barriers to ED OAC prescribing (eg, the competing demands of running an ED and lack of guaranteed follow-up care after discharge from an ED), should be used to support prescribing of OAC in the ED. Potential solutions are described.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Prescriptions; Electric Countershock; Emergency Medicine; Emergency Service, Hospital; Evidence-Based Practice; Hemorrhage; Humans; Medication Adherence; Risk Assessment; Stroke; Vitamin K

Factor Xa inhibitors and vitamin K antagonists (VKAs) are now recommended in treatment guidelines for preventing stroke and systemic embolic events in people with atrial fibrillation (AF). This is an update of a Cochrane review previously published in 2013.. To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for preventing cerebral or systemic embolic events in people with AF.. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2017), MEDLINE (1950 to April 2017), and Embase (1980 to April 2017). We also contacted pharmaceutical companies, authors and sponsors of relevant published trials. We used outcome data from marketing authorisation applications of apixaban, edoxaban and rivaroxaban that were submitted to regulatory authorities in Europe and the USA.. We included randomised controlled trials (RCTs) that directly compared the effects of long-term treatment (lasting more than four weeks) with factor Xa inhibitors versus VKAs for preventing cerebral and systemic embolism in people with AF.. The primary efficacy outcome was the composite endpoint of all strokes and systemic embolic events. Two review authors independently extracted data, and assessed the quality of the trials and the risk of bias. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. In case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects. We also performed a pre-specified sensitivity analysis excluding any open-label studies.. We included data from 67,688 participants randomised into 13 RCTs. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux, idrabiotaparinux, or rivaroxaban. The majority of the included data (approximately 90%) was from apixaban, edoxaban, and rivaroxaban.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in all of the included studies. Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin in participants with AF (OR 0.89, 95% CI 0.82 to 0.97; 13 studies; 67,477 participants; high-quality evidence).Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.78, 95% CI 0.73 to 0.84; 13 studies; 67,396 participants; moderate-quality evidence). There was, however, statistically significant and high heterogeneity (I. Treatment with factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in people with AF. The absolute effect of factor Xa inhibitors compared with warfarin treatment was, however, rather small. Factor Xa inhibitors also reduced the number of ICHs, all-cause deaths and major bleedings compared with warfarin, although the evidence for a reduction in the latter is less robust.

Topics: Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Humans; Intracranial Embolism; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic range and low international normalised ratio variability. The SAMe-TT2R2 score aims to identify those at risk for poor VKA control.. To evaluate the predictive value and clinical usefulness of the SAMe-TT2R2 score to identify those at risk for poor VKA control.. We performed a systematic review in MEDLINE and Embase for original research papers assessing the SAMe-TT2R2's relation to poor TTR. We performed a meta-analysis where scores ≥ 2 and ≥ 3 predicting TTR < 70%. When studies evaluated other cutoffs for TTR or SAMe-TT2R2, they were harmonised by multiple simulations with patient characteristics from the individual studies, if the data were available.. 16 studies were identified and used in the meta-analysis: 4 and 2 times directly, 8 and 8 times harmonised for scores ≥ 2 and ≥ 3, respectively (not all studies provided information about both cutoffs). The sensitivities and specificities were too heterogeneous to pool. The positive likelihood ratios were 1.25 (1.14-1.38) for a score ≥ 2, and 1.24 (1.09-1.40) for a score ≥ 3; the negative ones were 0.87 (0.82-0.93) and 0.96 (0.91-1.02), respectively. This shows that the post-test probabilities hardly differ from the prior probability (prevalence).. The SAMe-TT2R2 score does predict low TTR, but the effect is small. Its effect on individual patients is too limited to be clinically useful.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Humans; International Normalized Ratio; Likelihood Functions; Risk; Venous Thromboembolism; Vitamin K

The appropriate and safe peri-procedural anticoagulation schedule for patients on a direct oral anticoagulant (DOAC) undergoing AF ablation is not known. We aimed to evaluate the safety and efficacy of both continuous and minimally-interrupted novel oral anticoagulant (DOAC) strategies compared with uninterrupted vitamin K antagonist (VKA) for atrial fibrillation (AF) ablation.. We searched electronic databases for randomized or prospective controlled observational studies comparing DOAC (continuous or interrupted) versus uninterrupted VKA. The primary endpoint was major bleeding. Secondary endpoints were total bleeding (composite of major and minor bleeding) and symptomatic thromboembolism. Data were analyzed by random-effects modeling and sensitivity analyses performed according to study design and peri-procedural DOAC schedule.. Continuous and minimally-interrupted DOAC are both safe and non-inferior peri-procedural anticoagulation strategies compared with uninterrupted VKA for AF ablation. DOAC in general is associated with reduced major bleeding as demonstrated in pooled randomized studies.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Drug Administration Schedule; Humans; Risk Factors; Thromboembolism; Vitamin K

Non-vitamin K oral anticoagulants (NOACs) are increasingly prescribed for patients to treat or prevent arterial or venous thromboembolism. The following 4 NOAC agents are approved by the US Food and Drug Administration for clinical use: dabigatran etexilate, apixaban, edoxaban tosylate, and rivaroxaban. A good understanding of these agents' pharmacologic properties is important for surgeons given their marked differences compared with warfarin sodium. This review highlights key practical issues surrounding the use of NOACs in the perioperative setting.. The PubMed and Cochrane Library databases were searched for English-language studies from May 1, 2009, until May 1, 2017, for randomized clinical trials, meta-analyses, systematic reviews, observational studies, and clinical guidelines. From a systematic review of the published literature that included 70 articles and 166 404 patients, this study identified 5 key practical issues surrounding the use of NOACs in the perioperative setting. These include patient populations for which NOAC use is indicated and contraindicated, the timing of NOAC treatment cessation before invasive interventions, management of NOAC-treated patients requiring urgent interventions, the need for "bridging," and the timing of NOAC treatment's reinitiation after invasive interventions. Important findings are as follows: NOAC agents are not recommended for patients with mechanical heart valves or advanced kidney disease (creatinine clearance, <15 mL/min); minimal to no anticoagulant effect remains when therapy with a NOAC is withheld for 48 to 72 hours before surgery in the context of normal kidney function; a reversal agent is clinically available for dabigatran, while reversal agents for apixaban, edoxaban, and rivaroxaban are under regulatory review; and laboratory testing of the anticoagulant effects of NOACs are not routinely available. There is a paucity of high-quality data on the optimal timing of NOAC cessation and resumption in the perioperative period, particularly for patients who undergo procedures with high bleeding risk.. The anticoagulant effect of NOAC agents is predictable but not readily measurable in routine clinical practice. A number of uncertainties remain surrounding the use of these agents in the perioperative setting. Ongoing prospective studies and randomized clinical trials will provide greater clarity on these management issues in the near future.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Competence; Humans; Surgeons; Thromboembolism; Vitamin K

It has been documented that physical activity may increase the risk of atrial fibrillation (AF) in active or former competitive athletes. Different mechanisms are involved and responsible for the development of the arrhythmia, such as structural changes of the left atrium, influences of autonomic nervous system with enhanced vagal tone, and the use of prohibited substances with arrhythmogenic effects. Difficulties in the management of AF in athletes may derive from the low compliance to antiarrhythmic therapy and the selection of the most appropriate strategy for thromboembolic risk prevention. In fact, the majority of athletes are young, healthy, without any particular risk factor, except for arterial hypertension which can be the only risk factor in the evaluation of antithrombotic therapy with the CHA

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Athletes; Atrial Fibrillation; Blood Coagulation; Female; Humans; Hypertension; Male; Middle Aged; Risk Factors; Stroke; Thromboembolism; Vitamin K

Atrial fibrillation (AF) is the most common arrhythmia and its prevalence increases with age. Age also increases the risk of thromboembolism related to AF. As a result, elderly patients are at increased risk of AF-related stroke compared to younger patients. Age, however, also increases the risk of bleeding, including that of intracranial haemorrhage, an important cause of death and disability. Elderly patients with AF are, therefore, often undertreated due to the fear of bleeding complications, although recent data suggest an even greater net clinical benefit for anticoagulation in general in the elderly, even the very elderly, compared with younger patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, have become popular alternatives to vitamin K antagonists (VKAs) for anticoagulation in AF. The improved safety profile of NOACs may enable treatment of elderly patients that were previously untreated, further improving on this net clinical benefit. However, a number of factors, including renal impairment and multiple comorbidities, may elicit in elderly patients concerns with NOACs that are not seen in younger patients. Recent clinical data suggest that the use of NOACs offers a safer alternative to VKAs. However, on the basis of current evidence, it is not possible to simply recommend one NOAC over another in elderly adults. A personalised approach is recommended, accounting for individual patient factors.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Rivaroxaban; Treatment Outcome; Vitamin K

As model-based economic evaluations (MBEEs) are widely used to make decisions in the context of policy, it is imperative that they represent clinical practice. Here, we assess the relevance of MBEEs on dabigatran for the prevention of stroke in patients with atrial fibrillation (AF).. We performed a systematic review on the basis of a developed questionnaire, tailored to oral anticoagulation in patients with AF. Included studies had a full body text in English, compared dabigatran with a vitamin K antagonist, were not dedicated to one or more subgroup(s), and yielded an incremental cost-effectiveness ratio. The relevance of all MBEEs was assessed on the basis of ten context-independent factors, which encompassed clinical outcomes and treatment duration. The MBEEs performed for the United States were assessed on the basis of seventeen context-dependent factors, which were related to the country's target population and clinical environment.. The search yielded twenty-nine MBEEs, of which six were performed for the United States. On average, 54 percent of the context-independent factors were included per study, and 37 percent of the seventeen context-dependent factors in the U.S.. The share of relevant factors per study did not increase over time.. MBEEs on dabigatran leave out several relevant factors, limiting their usefulness to decision makers. We strongly urge health economic researchers to improve the relevance of their MBEEs by including context-independent relevance factors, and modeling context-dependent factors befitting the decision context concerned.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Cost-Benefit Analysis; Dabigatran; Decision Making; Female; Humans; Male; Models, Economic; Quality-Adjusted Life Years; Stroke; Surveys and Questionnaires; United States; Vitamin K

We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y

Topics: Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Observational Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Vitamin K

The Multimorbid Patient: Use of New Oral Anticoagulants in Patients with Chronic Kidney Disease Abstract. Increasing life expectancy in Western countries is associated with a high prevalence of multiple chronic diseases which is defined by the term "multimorbidity". Many of these patients suffer from chronic kidney disease (CKD) and thrombogenic comorbidities such as atrial fibrillation with the need for oral anticoagulation. For decades vitamin K antagonists have been exclusively prescribed for oral anticoagulation. However, due to altered pharmacokinetics and bioavailability of these drugs in CKD, a significant risk of bleeding exists. The introduction of direct oral anticoagulants as a new and promising alternative to vitamin K antagonists was -especially for CKD patients - highly anticipated. However, data from randomized studies are missing for older patients with advanced CKD. Consequently, a careful evaluation of the risk-benefit ratio is recommended for this sensitive patient population.. Zusammenfassung. Die zunehmende Lebenserwartung in den westlichen Ländern führt zu einer gleichzeitigen Zunahme chronischer Krankheiten, was mit «Multimorbidität» bezeichnet wird. Viele dieser Patienten leiden an chronischer Niereninsuffizienz (CKD) sowie thrombogenen Komorbiditäten wie z.B. Vorhofflimmern, weshalb eine orale Antikoagulation indiziert ist. Für lange Zeit standen lediglich die Vitamin-K-Antagonisten zur Verfügung. Aufgrund der unter anderem veränderten Pharmakokinetik sowie Bioverfügbarkeit dieser Medikamente bei CKD besteht jedoch gleichzeitig ein deutlich erhöhtes Blutungsrisiko. Die Einführung der direkten oralen Antikoagulanzien als neue und vielversprechende Alternative zu Vitamin-K-Antagonisten wurde daher insbesondere für die Population der CKD-Patienten mit grosser Spannung erwartet. Aufgrund der noch nicht ausreichenden Datenlage insbesondere bei älteren Patienten mit fortgeschrittener Niereninsuffizienz sollte das Risiko-Nutzen-Verhältnis vor Therapiebeginn sorgfältig evaluiert werden.

Topics: Anticoagulants; Arterial Occlusive Diseases; Atrial Fibrillation; Comorbidity; Contraindications; Coronary Disease; Dabigatran; Glomerular Filtration Rate; Kidney Failure, Chronic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thromboembolism; Vitamin K

Both atrial fibrillation (AF) and chronic kidney disease (CKD) are highly prevalent, especially with increasing age and associated comorbidities, such as hypertension, diabetes, heart failure, and vascular disease. The relationship between both AF and CKD seems to be bidirectional: CKD predisposes to AF while onset of AF seems to lead to progression of CKD. Stroke prevention is the cornerstone of AF management, and AF patients with CKD are at higher risk of stroke, mortality, cardiac events, and bleeding. Stroke prevention requires use of oral anticoagulants, which are either vitamin K antagonists (eg, warfarin), or the nonvitamin K antagonist oral anticoagulants (NOACs). While NOACs have been shown to be effective in mild-to-moderate renal dysfunction, there are a paucity of data regarding NOACs in severe and end-stage renal dysfunction. This review first discusses the evidence for NOACs in CKD. Second, we summarize the current knowledge regarding the efficacy and safety of NOACs to prevent AF-related stroke and systemic embolism in severe and end-stage renal disease.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Comorbidity; Glomerular Filtration Rate; Humans; Prognosis; Renal Insufficiency, Chronic; Thromboembolism; Vitamin K

Catheter ablation for atrial fibrillation (AF) is associated with a transitory increase in the risk of both thromboembolic and bleeding events. Evidence on the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients undergoing AF ablation mostly comes from small observational studies, underpowered to detect differences in clinical outcomes between NOACs and vitamin K antagonists (VKAs) treated patients. This updated meta-analysis aimed to determine the safety and efficacy of periprocedural anticoagulation with NOACs compared with VKAs in AF patients undergoing catheter ablation.. We searched MEDLINE, Cochrane library, and web sources for randomized and observational studies comparing periprocedural treatment with NOACs and VKAs in patients undergoing AF ablation. The primary safety endpoint was major bleeding events, and the primary efficacy endpoint was thromboembolic events (a composite of systemic thromboembolism, transient ischemic attack, and stroke).. Use of NOACs compared to VKAs significantly reduced the risk of bleeding in patients with AF ablation. Similarly, the risk of bleeding was lower with uninterrupted NOACs than with uninterrupted VKAs, and with interrupted NOACs than with interrupted VKAs. The rate of thromboembolic complications was extremely low in both study groups without any differences.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Loss, Surgical; Catheter Ablation; Drug Administration Schedule; Humans; Patient Safety; Postoperative Hemorrhage; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

Current guidelines recommend anticoagulation using warfarin with bridging parenteral anticoagulation or one of the non-vitamin K antagonist oral anticoagulants (NOACs) to prevent thromboembolic events in patients undergoing cardioversion for atrial fibrillation (AF). We aimed to compare by meta-analytical techniques, the safety and efficacy of NOACs versus warfarin in patients undergoing cardioversion.. PUBMED, EMBASE, Cochrane CENTRAL and CINAHL were searched electronically in addition to manual search for randomized controlled trials (RCTs) comparing NOACs and warfarin in patients undergoing cardioversion for AF. Mortality, major bleeding and ischemic and hemorrhagic stroke were compared between the two agents.. A total of 7 trials with 7588 total patients were included in the meta-analysis. NOACs, as compared to warfarin, resulted in similar risk of ischemic stroke [odds ratio (OR): 0.49 (95% confidence interval (CI): 0.20-1.19; P = 0.12], major bleeding [0.71 (0.37-1.38), P = 0.32], mortality [0.73 (0.32-1.67); P = 0.45], and hemorrhagic stroke [0.96 (0.11-8.70); P = 0.97]. The results were consistent across subgroup analyses.. Based on the current meta-analysis, NOACs and warfarin have comparable efficacy and safety in patients with atrial fibrillation undergoing cardioversion.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Electric Countershock; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K; Warfarin

In patients with atrial fibrillation (AF), oral anticoagulation with vitamin K antagonists (VKA) (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention with a 60-70% relative reduction in stroke risk compared with placebo. Mortality is reduced by 26%. VKA have a number of well-documented shortcomings which were overcome by non-vitamin-K oral anticoagulants (NOACs). Areas covered: Results of randomized trials for four NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have been published (ARISTOTLE, RE-LY, ENGAGE, ROCKET-AF). In this review, the authors discuss the results in subgroups of patients with prior transient ischemic attacks or ischemic stroke. In aggregate, the NOACs are superior to warfarin for secondary prevention and result in a 50% reduction in intracerebral hemorrhage. Apixaban was superior to aspirin in the AVERROES trial and had a similar rate of major bleeding complications. Expert opinion: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use. Aspirin should no longer be used for secondary stroke prevention in patients with AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Secondary Prevention; Stroke; Vitamin K

To assess the frequency of left atrium/left atrial appendage (LA/LAA) thrombus under treatment with non-vitamin K oral anticoagulants (NOACs) in comparison with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (AF).. PubMed, Web of Science™, EMBASE and the Cochrane Library databases were searched for studies comparing NOACs with VKAs in AF patients who underwent diagnostic transoesophageal echocardiography (TEE).. The findings of this meta-analysis suggest that NOACs are similar to VKAs regarding the frequency of LA/LAA thrombus in patients with AF. An unknown number of patients in the original studies did not receive sufficient anticoagulation for at least 3 weeks prior to TEE examination, and therefore the present results should be interpreted with caution. Systematic review registration- http://www.crd.york.ac.uk/PROSPERO . Unique identifier: PROSPERO CRD42017059293.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Heart Atria; Humans; PubMed; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Hemorrhage; Humans; Stroke; Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) is a progressive chronic disease characterized by exacerbations and periods of remission. It is estimated that up to 20% to 30% of those with AF also have coronary artery disease (CAD), and 5% to 15% will require percutaneous coronary intervention (PCI). In patients with concomitant AF and CAD, management remains challenging and requires a careful and balanced assessment of the risk of bleeding against the anticipated impact on ischemic outcomes (AF-related stroke and systemic embolism, as well as ischemic coronary events). Oral anticoagulation (OAC) is indicated for the prevention of AF-related stroke and systemic embolism, whereas antiplatelet therapy is indicated for the prevention of coronary events. Each offers a relative efficacy benefit (dual antiplatelet therapy [DAPT] is more effective than OAC alone in reducing cardiovascular death, myocardial infarction, stent thrombosis, and ischemic coronary events in a population with acute coronary syndromes [ACS]), but with a relative compromise (DAPT is significantly inferior to OAC for the prevention of stroke/systemic embolism in an AF population at increased risk of stroke). The purpose of this review is to explore the current evidence and rationale for antithrombotic treatment strategies in patients with both AF and CAD. Specifically, there is a focus on how to best tailor the therapeutic choices (OAC and antiplatelet therapy) to individual patients based on their underlying coronary presentation.

Topics: Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stroke; Vitamin K

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Renal Insufficiency; Risk Assessment; Secondary Prevention; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

Much new evidence on oral anticoagulation has come to light in recent years. Non-vitamin-K-dependent oral anti- coagulants (NOAC) have been developed and have been introduced into clinical practice. In this review, we present the current state of the evidence on anticoagulation for various indications with vitamin K antagonists (VKA) and with NOAC.. This review is based on pertinent articles retrieved by a selective search in PubMed (search terms: anticoagulation, atrial fibrillation, prosthetic valve, thrombosis, pulmonary embolism) and on specialty society recommendations and relevant guidelines from the years 2000-2018.. The main indications for oral anticoagulation are atrial fibrillation, venous thromboembolism, and status post heart valve replacement. In patients with atrial fibrillation and without valvular heart disease, anticoagulation is recommended for men with a CHA2DS2-VASc score ≥ 1 and for women with a score ≥ 2. NOAC for this indication are associated with a marginally lower rate of stroke than VKA (3.5% vs. 3.8%, number needed to treat [NNT] = 333) as well as a lower rate of major hemorrhage (5.1% vs. 6.2%, NNT = 91). NOAC are contraindicated for patients with mechanical heart valves. Anticoagulation with VKA can be predictably antagonized. Among the various types of NOAC, the anticoagulant effect of dabigatran can be safely antagonized with an antidote; no specific antidote is yet available for apixaban, rivaroxaban, or edoxaban.. The evidence base for anticoagulation over a time frame of several years is inadequate at present, and direct comparative data for the different types of NOAC are not yet available.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Prosthesis; Humans; Risk Assessment; Venous Thromboembolism; Vitamin K

Atrial fibrillation is more frequent in older patients, who have a higher risk of cardioembolic stroke and thromboembolism. Oral anticoagulant therapy is the standard of treatment for stroke prevention; however, under-prescription is still very common in older patients. The reasons underlying this phenomenon have not been systematically investigated, and true contraindications only partially account for it. An intimate skepticism on the real benefit-risk balance of oral anticoagulant therapy in the oldest patients seems to derive from the fact that most studies supporting it were conducted decades ago and included younger patients, with overall better functional and clinical status. In this review we will focus on the main barriers to anticoagulant therapy prescription in older patients and summarize the available evidences on the efficacy and safety of vitamin K antagonists and direct oral anticoagulants in this population. The encouraging evidence of a higher net clinical benefit of direct oral anticoagulants compared with warfarin should hopefully widen the treatment options also for frail individuals, thereby allowing a greater number of patients to be treated according to current international guidelines.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Vitamin K; Warfarin

Formal guidelines play an important role in disseminating the best available evidence knowledge and are expected to provide simple and practical recommendations for the most optimal management of patients with various conditions. Such guidelines have important implications for many disease states, which thereby could be more professionally managed in everyday clinical practice by clinicians with divergent educational backgrounds, and also more easily implemented in wards or outpatient clinics, eliminating inequalities in health care management. In this brief Viewpoint we provide an appraisal on the recommendations pertinent to the prevention of atrial fibrillation-related stroke or systemic thromboembolism, as provided in recently published guidelines for the management of this arrhythmia.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Practice Guidelines as Topic; Risk Assessment; Stroke; Thromboembolism; Vitamin K

Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted.. Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk; Stroke; Ticlopidine; Treatment Outcome; Vitamin K; Warfarin

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events. These AF patients may be denied oral anticoagulants, whilst evidence shows that the absolute benefits of oral anticoagulants are greatest in patients at highest risk. NOACs are an alternative to VKAs to prevent stroke in patients with "non-valvular AF", and NOACs may offer a greater net clinical benefit compared with VKAs, particularly in these high-risk patients. Physicians have to learn how to use these drugs optimally in specific settings. We review concrete clinical scenarios for which practical answers are currently proposed for use of NOACs based on available evidence for patients with kidney disease, elderly patients, women, patients with diabetes, patients with low or high body weight, and those with valve disease.

Topics: Administration, Oral; Aging; Anticoagulants; Antithrombins; Atrial Fibrillation; Body Weight; Diabetes Mellitus; Factor Xa Inhibitors; Heart Valve Diseases; Hemorrhage; Humans; Kidney Diseases; Risk Factors; Stroke; Vitamin K

Topics: Administration, Oral; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Factor Xa Inhibitors; Humans; Multicenter Studies as Topic; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Vitamin K; Warfarin

Cancer patients appear to be at increased risk for atrial fibrillation. Although surgery and chemotherapy exacerbate this risk, this association is observed even in the absence of any cancer-specific treatment. The underlying mechanism of this is likely multifactorial, but systemic inflammation and autonomic dysregulation are hypothesized to play critical roles. Cancer and atrial fibrillation are both independent risk factors for ischemic stroke; however, it is not clear whether this translates to an increased risk of stroke in patients with both comorbidities. As such, commonly used risk stratification tools including the CHADS2 score currently do not take cancer into account as a variable and it is possible that stroke risk is underestimated in this population. There is a paucity of data regarding anticoagulant choice in cancer patients with atrial fibrillation. Vitamin K antagonists are often preferred over direct oral anticoagulants; however, this may be changing in the near future as new trials specific to this patient population emerge.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Neoplasms; Risk Factors; Stroke; Vitamin K

Since direct oral anticoagulants (DOAC) have become available, use of anticoagulant treatment has become easier and safer-for patients suffering from thromboembolic diseases as well as for patients with atrial fibrillation: Because of constant bioavailability, fixed dose regimen treatment is possible, monitoring not necessary and severe bleeding complications-particularly intracranial hemorrhages-rare in comparison to vitamin K anticoagulants. To gain all these advantages, it is essential to give DOAC in the correct dosage. Dose reduction of single DOAC has to be considered depending on underlying disease, body weight and renal function. DOAC are not allowed in patients with artificial heart valves, in pregnancy and in children. In case of severe bleeding complications under DOAC treatment, prothrombin complex concentrates is one treatment option. For dabigatran an antidote is available.

Topics: Administration, Oral; Anticoagulants; Antidotes; Atrial Fibrillation; Biological Availability; Body Weight; Dabigatran; Humans; Thromboembolism; Vitamin K

Oral anticoagulation therapy has reduced the risk of ischaemic stroke and improved the outcomes for patients with atrial fibrillation considerably. The emergence of the non-vitamin K oral anticoagulants as alternatives to vitamin K antagonists has significantly changed the practice of stroke prevention in atrial fibrillation. As the main complication with antithrombotic therapy is bleeding, physicians should always balance the risk of ischaemic stroke against intracranial haemorrhage and intervene where appropriate to reduce both risks. Individual approach is often mandatory due to heterogeneity of the risks and patient preferences. The purpose of this review is to summarise the current knowledge of the oral anticoagulation therapy in atrial fibrillation patients and guide physicians with the management of anticoagulants based on data from clinical trials and systematic reviews.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Risk Assessment; Stroke; Vitamin K

The findings from the observational studies comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban).. The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance-weighted random effects models.. A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57-1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83-1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67-0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59-1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66-0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77-1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40-1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59-1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding.. Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thromboembolism; Vitamin K

The efficacy and safety of warfarin for stroke prevention in atrial fibrillation (AF) depend on the time in the therapeutic range (TTR) with an international normalised ratio (INR) of 2.0-3.0. This meta-analysis focused the relative efficacy and safety of non-VKA oral anticoagulants (NOAC) compared with warfarin at different thresholds of centre's TTR (cTTR).. We searched PubMed, Embase, CENTRAL and websites of regulatory agencies, limiting searches to randomized phase 3 trials. Primary outcomes were stroke or systemic embolism (SSE) and major or non-major clinically relevant (NMCR) bleeding. We used a random-effects model to pool effect on outcomes according to different thresholds of cTTR.. Four TTR sub-studies with a total of 71,222 patients were included. The benefit of NOAC in reducing SSE compared with warfarin was significantly higher in patients at cTTR<60% (HR 0.79, 95% CI 0.68-0.90) and at 60% to <70% (0.82, 0.71-0.95) but not at ≥70% (1.00, 0.82-1.23) with a significant interaction for cTTR<70% or ≥70% (p=0.042). The risk of major or NMCR bleeding was significantly lower with NOAC as compared with warfarin in patients at all sub-groups (0.67, 0.54-0.83 for patients at cTTR<60% and 0.75, 0.63-0.89 at 60% to <70%) except for cTTR≥70% (HR 0.84, 0.64-1.11), but the interaction for cTTR<70% or ≥70% was not statistically significant (p=0.271).. The superiority in efficacy of NOAC compared with warfarin for stroke prevention is lost above a cTTR threshold of approximately 70%, but the relative safety appears to be less modified by the centre-based quality of INR control.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; International Normalized Ratio; Randomized Controlled Trials as Topic; Stroke; Vitamin K; Warfarin

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, AF is associated with an increased risk of thromboembolism and stroke, according to progressive decline of glomerular filtration rate (GFR). However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25 ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <25 ml/) and those on dialysis.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; Thromboembolism; Vitamin K

Intracardiac thrombus is a potentially life-threatening condition associated with atrial fibrillation (AF), with a high risk of embolic complications. Oral anticoagulation (OAC) therapy is the first-line treatment for its prevention or resolution. For many patients, traditional OAC treatment using vitamin K antagonists (VKAs; e.g., warfarin) is limited by several factors and the advent of non-VKA oral anticoagulants (NOACs), with improved efficacy and safety profiles, has provided additional treatment options. However, studies are limited in number and are mostly case reports or series, with only one published modest-size prospective multicenter cohort study for rivaroxaban. No randomized controlled trials have been performed. Given the available data thus far, albeit weak, NOACs offer a possible alternative to VKAs for treating intracardiac thrombi.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; Multicenter Studies as Topic; Prospective Studies; Rivaroxaban; Vitamin K

The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit-risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD).. Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta-analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60-0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24-0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69-0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25-0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20-2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77-2.10]).. Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Female; Heart Valve Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up.. A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method.. Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74,. In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.

Topics: Atrial Fibrillation; Brain Ischemia; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Stroke; Vitamin K

Oral anticoagulation with vitamin K antagonists (VKA) was the cornerstone of stroke prevention in atrial fibrillation (AF). This review article presents the state of the art, with regard to the treatment options developed over the past few years, the new oral anticoagulants (NOAC). A search in PubMed for relevant published studies has been performed. Dabigatran and apixaban were superior to warfarin to reduce stroke risk or systemic embolism ; dabigatran, rivaroxaban and edoxaban were non-inferior. All NOAC are globally non-inferior to warfarin for stroke prevention in non-valvular AF and they have a superior safety profile, with a reduced intracranial bleeding risk. They are now the first choice for treatment.. Les antagonistes de la vitamine K (AVK) ont été pendant longtemps la référence comme prévention de l’accident vasculaire cérébral (AVC) chez les patients souffrant de fibrillation auriculaire (FA). Cet article de revue propose une mise à jour des options thérapeutiques développées ces dernières années, à savoir les nouveaux anticoagulants oraux (NACO). Une recherche des études pertinentes a été effectuée dans PubMed. Il apparaît ainsi que le dabigatran et l’apixaban sont supérieurs à la warfarine pour réduire les AVC et les embolies systémiques ; le dabigatran, le rivaroxaban et l’édoxaban sont non inférieurs. Tous les NACO sont donc globalement non inférieurs à la warfarine pour prévenir les AVC dans la FA non valvulaire et ils ont un profil de sécurité supérieur, avec un moindre risque d’hémorragie intracrânienne. Ils représentent maintenant le traitement de premier choix.

Topics: 4-Hydroxycoumarins; Administration, Oral; Anticoagulants; Atrial Fibrillation; Drugs, Investigational; Humans; Indenes; Stroke; Vitamin K

Atrial fibrillation (AF) is associated with a markedly increased risk of thromboembolic events, particularly in patients with valvular AF. Recent trials comparing vitamin K antagonists with non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in AF excluded most patients with valvular AF. Although the definition of valvular AF is disputed, the lack of evidence regarding the use of NOACs for these patients is not. We discuss the definition of valvular AF, the risk of thromboembolism, and the antithrombotic treatment for stroke prevention in these patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Stroke; Thromboembolism; Vitamin K

To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).. We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.. We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke Scale [NIHSS. DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain; Cerebral Hemorrhage; Cross-Sectional Studies; Female; Humans; Male; Observational Studies as Topic; Prospective Studies; Stroke; Treatment Outcome; Vitamin K

This meta-analysis sought to assess the safety and efficacy of uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) versus uninterrupted vitamin K antagonists in atrial fibrillation (AF) patients undergoing catheter ablation. Electronic databases were searched for randomized trials (RCTs) and observational studies that compared uninterrupted NOACs versus uninterrupted vitamin K antagonists in the catheter ablation of AF. Safety outcomes included major bleeding, total bleeding, minor bleeding, and cardiac tamponade. Efficacy outcomes were symptomatic thromboembolism and symptomatic stroke/transient ischemic attack. Summary estimate risk ratios (RRs) were constructed primarily with a DerSimonian-Laird model. Thirteen studies (3 RCTs and 10 observational studies) with 4,878 patients were included. The risk of major bleeding (RR 0.83, 95% confidence interval [CI] 0.46 to 1.50, p = 0.53), total bleeding (RR 0.90, 95% CI 0.71 to 1.15, p = 0.41), minor bleeding (RR 0.98, 95% CI 0.80 to 1.21, p = 0.85), cardiac tamponade (RR 0.85, 95% CI 0.43 to 1.69, p = 0.65), symptomatic thromboembolism (RR 0.92, 95% CI 0.26 to 3.31, p = 0.90), and symptomatic stroke/transient ischemic attack (RR 1.03, 95% CI 0.29 to 3.65, p = 0.97) was similar in both groups. The quality of evidence for both major bleeding and symptomatic thromboembolism was moderate for RCTs and very low for observational studies. In conclusion, the use of uninterrupted NOACs in AF catheter ablation appears to be safe and efficacious. The evidence is not of high quality; thus, further high-quality RCTs are needed to confirm these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Global Health; Humans; Incidence; Risk Factors; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Fibrinolytic Agents; Humans; Inappropriate Prescribing; Review Literature as Topic; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

The worldwide increase in the aging population and the associated increase in the prevalence of atrial fibrillation and venous thromboembolism as well as the widespread use of direct oral anticoagulants (DOAC) have resulted in an increase of the need for the management of bleeding complications and emergency operations in frail, elderly patients, in clinical practice. When severe bleeding occurs, general assessment should include evaluation of the bleeding site, onset and severity of bleeding, renal function, and concurrent medications with focus on anti-platelet drugs and nonsteroidal anti-inflammatory drugs (NSAID). The last intake of the DOAC and its residual concentration are also relevant. The site of bleeding should be immediately localized, anticoagulation should be interrupted, and local measures to stop bleeding should be taken. In life-threatening bleeding or emergency operations immediate reversal of the antithrombotic effect may be indicated. If relevant residual DOAC-concentrations are expected and surgery cannot be postponed, prothrombin complex concentrate (PCC) and/or a specific antidote should be given. While idarucizumab, the specific antidote for dabigatran, has been recently approved for clinical use, the recombinant factor X protein andexanet alfa, an antidote for the reversal of inhibitors of coagulation factor Xa, and ciraparantag, a universal antidote, are not available. Future cohort studies are necessary to assess the efficacy and safety of specific and unspecific reversal agents in "real-life" conditions. This was the rationale for introducing the RADOA-registry (RADOA: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists), a prospective non-interventional registry, which will evaluate the effects of specific and unspecific reversal agents in patients with life-threatening bleeding or emergency operations either treated with DOACs or vitamin K antagonists.. Durch eine weltweit alternde Bevölkerung nehmen Vorhofflimmern und venöse Thromboembolien und dadurch auch der Einsatz direkter oraler Antikoagulantien (DOAK) deutlich zu. Das Management von Blutungskomplikationen und Notfalloperationen bei diesen fragilen, alten Patienten stellt eine Herausforderung im klinischen Alltag dar. Bei Auftreten schwerer Blutungen sollten der Ort der Blutung, der Beginn und Schweregrad, sowie die Nierenfunktion und Begleitmedikationen wie Thrombozytenaggregationshemmer oder nichtsteroidale Antirheumatika (NSAR) Berücksichtigung finden. Der Zeitpunkt der letzten Tabletteneinnahme sowie die Restkonzentration des DOAK bei Aufnahme sind ebenfalls relevant. Die Antikoagulation sollte sofort unterbrochen und lokale Maßnahmen ergriffen werden, um die Blutung zu stillen. Bei lebensbedrohlicher Blutung oder rasch notwendiger Notfalloperation sollte der anti-koagulierende Effekt sofort aufgehoben werden. Die Gabe von PPSB kann erwogen werden, wenn spezifische Antidots nicht zur Verfügung stehen. Wenn relevante DOAK-Rest-konzentrationen vermutet werden und die Operation nicht aufgeschoben werden kann, dann sollten PPSB und/oder ein spezifisches Antidot präoperativ appliziert werden. Während Idarucizumab, das spezifische Antidot für Dabigatran, inzwischen zur Behandlung zugelassen ist, sind der rekombinante Faktor X Andexanet Alfa, der als Antidot gegen Faktor X-Inhibitoren wirkt und Ciraparantag, ein universelles Antidot, noch nicht für die klinische Anwendung verfügbar. Zukünftige Studien und Register sollten Effektivität und Sicherheit spezifischer und unspezifischer Gegenmittel im klinischen Alltag untersuchen. Diese Überlegungen haben zur Etablierung des RADOA-Registers (RADOA: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists) geführt, ein prospektives, multizentrisches, nicht-interventionelles Register, das die Ef-fektivität spezifischer und unspezifischer Gegenmittel bei Patienten mit lebensbedrohlichen Blutungen oder Notfalloperation unter Behandlung mit DOAK oder Vitamin-K-Antagonisten erfassen und auswerten wird.

Topics: Administration, Oral; Aged; Anticoagulants; Antidotes; Atrial Fibrillation; Emergency Medical Services; Frail Elderly; Hemorrhage; Humans; Population Dynamics; Prothrombin; Registries; Risk Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

Direct oral anticoagulants (DOACs) are increasingly prescribed substances in patients with indication for effective anticoagulation. Patients with chronic kidney disease (CKD) have a high burden of cardiovascular risk and are more likely to develop atrial fibrillation (AF) than patients without CKD. Patients with mild to moderate CKD benefit from DOACs, especially when having intolerance to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients with rare renal disease and hypercoagulabilic state. DOACs are to a large extent eliminated by renal excretion. Since prospective randomised data in CKD patients are sparse, the decision for anticoagulative therapy is challenging especially in patients with severe renal impairment. The direct factor Xa-inhibitors are approved for use even in patients with an estimated glomerular filtration rate (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a regular basis is essential before initiation and after start of DOAC, especially for patients at risk for acute renal failure (elderly, diabetics, patients with preexisting kidney disease). None of the DOACs is approved in CKD patients with end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors. In these patients conventional therapy with VKA is the only option, which has to be monitored closely since it has potential adverse effects.. Die direkten oralen Antikoagulantien (DOAK) werden zunehmend häufiger bei Patienten mit einer Indikation für eine effektive Antikoagulation verordnet. Im Vergleich zu Patienten ohne chronische Nierenerkrankung (CKD) haben Patienten mit CKD ein höheres kardiovaskuläres Risiko und eine höhere Wahrscheinlichkeit, Vorhofflimmern zu entwickeln. Die Behandlung mit DOAK ist bei Patienten mit milder bis mäßiger CKD von Vorteil, insbesonde-re wenn eine Unverträglichkeit gegen Vitamin-K-Antagonisten (VKA) besteht. DOAK können in Einzelfällen auch bei Patienten mit seltenen Nierenerkrankungen und Hyperkoagulabilität eingesetzt werden. Die DOAK werden zu einem großen Teil renal eliminiert. Da prospektive, randomisierte Daten zu CKD-Patienten rar sind, ist die Entscheidung für eine Antikoagulation schwierig, insbesondere bei Patienten mit deutlich eingeschränkter Nierenfunktion. Die direkten Faktor-Xa-Hemmer sind auch bei Patienten mit einer geschätzten glomerulären Filtrationsrate (GFR) von 15 bis 30 ml/min zugelassen. Es ist jedoch notwendig, die Nierenfunktion vor und nach Beginn der DOAK sorgfältig und regelmäßig zu evaluieren, besonders bei Patienten mit einem höheren Risiko für ein akutes Nierenversagen (Ältere, Diabetiker, Patienten mit bekannter Nierenerkrankung). Kein DOAK ist bei CKD-Patienten mit terminaler Nierenerkrankung, ob mit oder ohne Dialysetherapie, zugelassen. DOAK sind nicht empfohlen bei nierentransplantierten Patienten, die unter Immunsuppression mit Calcineurin-Hemmern stehen. Bei diesen Patienten ist die konven-tionelle Therapie mit VKA die einzige Möglichkeit und muss aufgrund potenziell uner-wünschter Nebenwirkungen engmaschig kontrolliert werden.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Contraindications; Factor Xa Inhibitors; Humans; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Risk Factors; Venous Thromboembolism; Vitamin K

Atrial fibrillation (AF) occurs with a prevalence of 1 % in the general population, up to 8 % in patients over 80 years of age and can lead to palpitations, tachycardia, hospitalization for heart failure and stroke. In order to prevent strokes, oral anticoagulation is necessary. In the 2016 guidelines for the management of atrial fibrillation, non vitamin K anticoagulants (NOACs) are preferred among vitamin K anticoagulants due to less severe bleeding, especially intracranial haemorrhage. There is also no longer evidence for antiplatelet therapy in AF. Apart from randomized controlled trials it has been shown in real world data that use of NOACs is safe and feasible. NOACs are not indicated in patients with mechanical valve replacement and valvular atrial fibrillation. Since November 2015 the first specific antidote for dabigatran is available in Germany, a factor Xa antidote (apixaban, rivaroxaban, edoxaban) is being tested in a phase III study.

Topics: Anticoagulants; Atrial Fibrillation; Guidelines as Topic; Humans; Stroke; Thromboembolism; Vitamin K

The thromboembolic risk of atrial fibrillation (AF) is significantly mitigated by oral anticoagulation (OAC) therapy, albeit at an increasing bleeding risk. The general principle is that the potential harm conferred by possible bleeding must not exceed the expected protective benefit of OAC. Over the recent years, the CHA2DS2-VASc score has been proven to be superior to other scores in identifying 'low risk' AF patients. However, even this latest score does not incorporate all possible risk factors causing a high thromboembolic risk, while the individual components of the CHA2DS2-VASc score do not seem to carry equal thromboembolic risk. Thus, the quest for more reliable risk stratification schemes and identification of "truly low-risk" patients has been continued.. In this article, data concerning the risk stratification schemes and particularly the CHA2DS2-VASc score of 1 and 0, are critically reviewed and a practical algorithm is proposed for all and more specifically for the "low-risk" patients.. A variety of clinical, echocardiographic, genetic and biochemical or coagulation parameters can also predict adverse thromboembolic events in AF patients. Nevertheless, the addition or adoption of more complex schemes may defeat the purpose of simplicity and practicality, demanding more extensive and costly assessments to decide on a relatively simple question, that of the need for anticoagulation. In the era of non-vitamin K oral anticoagulants (NOACs) proven equivalent or superior to vitamin K antagonists (VKAs), this may not be necessary any more, and a simple recommendation of dispensing OAC therapy almost to every patient afflicted by AF may prove to be a more practical and a ubiquitous approach, as long as safety is ensured by these newer agents.. The accumulated evidence appears compelling that at least those with a CHA2DS2- VASc score of ≥1, should receive OAC. With regards to those with a CHA2DS2-VASc score of 0, one may wish to consider additional risk factors (Figure 1) beyond those in scores to decide whether there is a need for thromboembolic protection that outweighs the bleeding risk, preferably with use of NOACs. Finally, an individualized strategy and clinical judgement may be necessary by assessing patient's clinical and financial status, preferences and choices in a shared decision-making or participatory medicine approach.

Topics: Algorithms; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Practice Guidelines as Topic; Stroke; Vitamin K

Nonvalvular atrial fibrillation (AF) is a risk factor for stroke in elderly patients. Although warfarin has been used to prevent AF-associated stroke for more than 50 years, non-vitamin K antagonist oral anticoagulants (NOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban recently have been developed to overcome the disadvantages of warfarin. Based on the results of NOAC clinical trials, Savelieva and Camm made recommendations regarding selection of NOACs in patients with nonvalvular AF. Recent accumulating evidence indicates that NOACs work differently in Asian and non-Asian individuals. In this review, we discuss the results of the large, randomized, phase 3 international clinical trials on NOACs, the subanalyses of Asians, and a Japanese phase 3 clinical trial of rivaroxaban to discriminate Japanese patient-specific characteristics with regard to their responses to NOACs and make recommendations. Our analysis revealed that rivaroxaban decreased the incidence of gastrointestinal (GI) bleeding compared with warfarin in Japanese patients. The efficacy results showed that rivaroxaban significantly decreased the incidence of ischemic stroke (hazard ratio: 0.40, 95% confidence interval: 0.17-0.96) compared with warfarin. The lower incidence of GI bleeding and ischemic stroke may be specific to Japanese patients. Based on the present and previous results, the following recommendations regarding the selection of NOACs are added in the Camm chart for Japanese patients: edoxaban for patients with a high risk of bleeding and those with a previous stroke; and rivaroxaban for patients with a high risk of ischemic stroke and a low bleeding risk, and those with previous GI bleeding.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Incidence; Japan; Stroke; Vitamin K

The use of vitamin K antagonists (VKAs) in hemodialysis patients with atrial fibrillation (AF) is controversial. No randomized trials are available and observational studies have yielded conflicting results, engendering a large clinical practice variability and physician uncertainty. An unresolved but highly relevant question is whether AF poses a true risk of ischemic stroke in hemodialysis and whether any form of oral anticoagulation is therefore warranted.. We conducted a systematic review of studies that compared the incidence of ischemic stroke and bleeding in hemodialysis patients with AF taking VKA and those not taking VKA. When hemodialysis patients had been pooled with peritoneal dialysis, kidney transplant, or stage V chronic kidney disease patients, unpublished outcome data of the hemodialysis subgroup were obtained through personal communication. The main outcome measures were ischemic stroke/thromboembolic events, all-cause mortality, major bleeding, and hemorrhagic stroke. Combined hazard ratios (HRs) and 95% CIs were calculated using a random-effects model.. Twelve prospective or retrospective cohort studies were included in the meta-analysis, totaling 17,380 hemodialysis patients of whom 4,010 (23.1%) received VKA. In VKA-treated patients, mean CHADS. Our meta-analysis revealed a trend for a reduction of the risk of ischemic stroke in hemodialysis patients with AF treated with VKA. The true protective effect may have been underestimated, owing to inclusion of low-risk patients not expected to benefit from anticoagulation and to suboptimal anticoagulation. However, assessment of the overall effect of VKA in hemodialysis patients should also take into account the increased risk of bleeding, in particular of hemorrhagic stroke. Whether new oral anticoagulants provide a better benefit-risk ratio in hemodialysis patients should be the subject of future trials.

Topics: Anticoagulants; Atrial Fibrillation; Cause of Death; Cerebral Hemorrhage; Hemorrhage; Humans; Kidney Failure, Chronic; Mortality; Proportional Hazards Models; Renal Dialysis; Stroke; Thromboembolism; Vitamin K; Warfarin

Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for more than 50 years. VKAs are mainly used for the prevention of stroke in patients with atrial fibrillation (AF) and the treatment and secondary prevention of venous thromboembolism. In the past 5 years, four new agents-the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or non-VKA oral anticoagulants]-have been approved for these and other indications. Despite these new treatment options, the VKA warfarin currently remains the most frequently prescribed oral anticoagulant. The availability of DOACs provides an alternative management option for patients with AF, especially when the treating physician is hesitant to prescribe a VKA owing to associated limitations, such as food and drug interactions, and concerns about bleeding complications. Currently available real-world evidence shows that DOACs have similar or improved effectiveness and safety outcomes compared with warfarin. Treatment decisions on which DOAC is best suited for which patient to maximize safety and effectiveness should take into account not only clinically relevant patient characteristics but also patient preference. This article reviews and highlights real and perceived implications of VKAs for the prevention of stroke in patients with non-valvular AF, with specific reference to their strengths and weaknesses compared with DOACs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Stroke; Vitamin K

Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists. New evidences have suggested their use in treatment of elderly people, in patients with renal insufficiency or with antiphospholipid antibody syndrome. In addition, the use of antidotes, which rapidly reverse the anticoagulant effect of the NOACs, could be useful in bleeding, during emergency procedures, or in case of overdose.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Pyrazoles; Pyridones; Stroke; Vitamin K

Few data are available about safety of vitamin K antagonists (VKAs) in patients with clinical/demographic characteristics predisposing to an increased risk of bleeding. We performed a meta-analysis to evaluate the safety of VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) in the following subgroups of "high-risk" patients: elderly patients, patients with low body weight and patients with impaired renal function.. Major electronic databases were systematically searched to identify randomized controlled trials (RCTs) addressing this issue. Pooled Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for each outcome using a random effects model.. Eleven RCTs for a total of 41,015 patients treated with VKAs (25,901 with AF and 15,114 with VTE) were included. We found a significant association between age>75years and bleeding in patients receiving VKAs (RR: 1.62, 95%CI: 1.28-2.05; P<0.0001). Moreover, the prevalence of bleeding events under VKAs was significantly higher in patients with low body weight (RR: 1.20, 95%CI: 1.03-1.40; P=0.02) and in those with impaired renal function (RR: 1.59, 95%CI: 1.30-1.94; P<0.00001). Results were confirmed when separately analyzing data on AF and VTE. Regression models showed that treatment duration did not impact on the differences found in the safety profile of VKAs in different settings analyzed.. Results of our meta-analysis suggest an increased risk of bleeding complications in "high-risk" patients. Although all results are significant, other studies focused on this issue are warranted to further validate these results.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Venous Thromboembolism; Vitamin K; Warfarin

Currently there is lack of head-to-head comparisons between different Non-Vitamin K Antagonist Oral Anticoagulants (NOACs), especially in more risky subgroups, as those with chronic kidney disease (CKD).. We assessed the relative efficacy and safety of the four NOACs on the market in a systematic review and network meta-analysis of patients with atrial fibrillation (AF) and moderate CKD enrolled in the phase 3 randomized trials. A Bayesian framework was used to perform the network meta-analysis. Treatment hierarchy was assessed by surface under the cumulative ranking (SUCRA) curves.. Five randomized trials including 13,878 AF patients with moderate CKD were identified. Full/Single dose NOACs were associated with significant reductions in the odds of stroke/systemic embolism (odd ratio [OR] 0.79, 95% credible intervals [CrI] 0.67-0.94) and major bleeding (OR 0.74, 95% CrI 0.65-0.86) compared with Warfarin. Dabigatran 150 had the highest probability of being ranked first with respect to efficacy (SUCRA 0.96), whereas Apixaban had the second highest (SUCRA 0.67); Dabigatran 110, Rivaroxaban and Edoxaban High-Dose showed similar probabilities of being ranked first for efficacy (SUCRA 0.54, 0.53, 0.51, respectively); with respect to safety, only Apixaban and Edoxaban High Dose had a probability >50% of being ranked first (SUCRA 0.84 and 0.61, respectively).. Indirect comparisons generated the hypothesis that Apixaban and Edoxaban High-Dose might be more likely associated with a better net clinical profile in AF patients with moderate CKD. These findings may potentially guide physicians in selecting the most appropriate NOAC for each patient, while waiting for dedicated evidences.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Network Meta-Analysis; Renal Insufficiency, Chronic; Thromboembolism; Vitamin K

In patients with atrial fibrillation (AF), the safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) vs warfarin according to diabetes mellitus (DM) status are not completely characterized. We performed a meta-analysis to clarify whether in these patients the strategy of oral anticoagulation should be tailored to diabetes status. In this study-level meta-analysis, we included 4 randomized phase III trials comparing NOACs and warfarin in patients with nonvalvular AF; a total of 18 134 patients with DM and 40 454 without DM were overall considered. Incidence of the following outcome measures was evaluated during the follow-up: stroke or systemic embolism, ischemic stroke, major bleeding, intracranial bleeding, and vascular death. Use of NOACs compared with warfarin reduced stroke/systemic embolism in diabetic (Risk Ratios [RR] 0.80, 95% CI 0.68-0.93; P = .004) and nondiabetic patients (RR 0.83, 0.73-0.93; P = .001) (P for interaction .72). No interaction between diabetes status and benefits of NOACs was found for the occurrence of ischemic stroke, major bleeding, or intracranial bleeding (P for interaction >.05 for each comparison). Reduction of vascular death rates with NOACs was significant in diabetic patients (4.97% vs 5.99% with warfarin; RR 0.83, 0.72-0.96; P = .01), in whom absolute the reduction of this outcome measure was higher than in nondiabetics (1.02% vs 0.27%), although no interaction was present (P = .23). Results of this meta-analysis support the safety and efficacy of NOACs compared with warfarin in diabetic patients with nonvalvular AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Diabetes Complications; Diabetes Mellitus; Humans; Prognosis; Randomized Controlled Trials as Topic; Safety; Stroke; Vitamin K; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and atrial fibrillation (AF). However, there is insufficient data concerning the periinterventional, perioperative, and intensive care management of patients on NOACs. Therefore, the recommendations regarding this management rely on pharmacokinetics of the particular NOAC in combination with the individual patient's characteristics, bleeding risk of the planned intervention/surgery, and urgency of the procedure. This review summarizes evidence and recommendations regarding the optimal periinterventional/perioperative antithrombotic management of patients on NOACs.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Atrial Fibrillation; Critical Care; Drug Interactions; Half-Life; Hemorrhage; Humans; Kidney Failure, Chronic; Pulmonary Embolism; Risk Factors; Surgical Procedures, Operative; Thromboembolism; Venous Thrombosis; Vitamin K

Cardiovascular mortality of hemodialysis patients remains a major problem. The prevalence and incidence of atrial fibrillation in this population are more important than in the general population. The indication of antivitamin K therapy (AVK) in this context of atrial fibrillation must be weighted against the increased risk of bleeding. Unfortunately, and contrary to the general population, an indication of anticoagulation based on embolic or hemorrhagic risk scores is not as clearly established in the hemodialysis population. No prospective randomized study has investigated the benefit/risk balance of anticoagulant treatment in hemodialysis subjects. This article is a review of the current literature on this topic, showing the prevalence of thromboembolic but also bleeding events in the hemodialysis population. The impact of AVK treatment in this specific population is also reviewed. To the best of our knowledge, the indication of treatment must be individualized.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Renal Dialysis; Stroke; Vitamin K

Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.. This study aimed to determine relative safety and efficacy of NOACs in patients with VHD.. We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.. Compared with warfarin, the rate of SSEE in patients treated with higher-dose NOACs was lower and consistent among 13,585 patients with (RR: 0.70; 95% CI: 0.58 to 0.86) or 58,098 without VHD (RR: 0.84; 95% CI: 0.75 to 0.95; interaction p = 0.13). Major bleeding in patients on higher-dose NOACs versus warfarin was similar and consistent among patients with (RR: 0.93; 95% CI: 0.68 to 1.27) or without VHD (RR: 0.85; 95% CI: 0.70 to 1.02; interaction p = 0.63 for VHD/no-VHD difference). Intracranial hemorrhage was lower with higher-dose NOACs than with warfarin irrespective of VHD (RR: 0.47; 95% CI: 0.24 to 0.93, and 0.49; 95% CI: 0.41 to 059, respectively; interaction p = 0.91). No protective effect of higher-dose NOACs in preventing all-cause death seemed to be present in patients with VHD versus without VHD (RR:1.01; 95% CI: 0.90 to 1.14 vs. RR: 0.88; 95% CI: 0.82 to 0.94, respectively; interaction p = 0.03).. High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.

Topics: Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Hemorrhage; Humans; Stroke; Vitamin K

Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Decision Making; Humans; Intracranial Hemorrhages; Stroke; Thromboembolism; Vitamin K

Atrial fibrillation is the most common cause of stroke. Treatment with anticoagulants in patients with atrial fibrillation reduces embolic complications of the disease including stroke. However, the commonly used anticoagulant has a narrow therapeutic index, requires routine monitoring, and has numerous drug and food interactions leading to less than optimal rates of adherence. Inhibition of clotting factor Xa has been evaluated as a potential target for anticoagulation therapy with the hypothesis that using target-specific therapy will alleviate some of the dosing variability observed with the vitamin K antagonist. Three factor Xa inhibitors are currently indicated for use in nonvalvular atrial fibrillation. Similar to the vitamin K antagonist, warfarin, all of the factor Xa inhibitors are administered orally. Rivaroxaban and edoxaban are dosed once daily while apixaban is dosed twice daily. All three agents have demonstrated noninferiority when compared with current standard treatment with warfarin for efficacy and safety outcomes. The therapeutic dose of factor Xa inhibitors vary based on renal function. Unlike warfarin, there are no currently available antidotes for the factor Xa inhibitors although this is an area of interest for current and future studies. In the event of a life-threatening bleed there are established management strategies to reverse the bleeding effects of the factor Xa inhibitors.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Drug Monitoring; Factor Xa Inhibitors; Hemorrhage; Humans; Stroke; Vitamin K

Patients at thromboembolic risk with non-valvular atrial fibrillation (AF) can now be managed either with a vitamin K antagonist (VKA) or with a fixed dose of a non-VKA oral anticoagulant (NOAC), while patients with valvular AF have been restricted to VKAs on the basis of a potentially higher risk and different mechanism of thrombosis, and the lack of sufficient data on the efficacy of NOACs. The terms 'non-valvular AF' and 'valvular AF' have not been however consistently defined. 'Valvular' AF has included any valvular disorder, including valve replacement and repair. In AF with rheumatic mitral disease, observational studies strongly suggest that VKA treatment is valuable. These patients have not been included in NOAC trials, but there is also no stringent argument to have excluded them. This is at sharp variance from patients with mechanical valves, also excluded from the pivotal Phase III trial comparing warfarin with NOACs, but in whom a single Phase II trial of dabigatran etexilate against VKA treatment was stopped prematurely because of increased rates of thromboembolism as well as increased bleeding associated with dabigatran. Until more data are available, such patients should be therefore managed with VKAs. We here propose an open-label randomized trial of one of the NOACs against the best of treatment available in regions of the world in which rheumatic heart disease is still highly prevalent, aiming at showing the superiority of the NOAC used against current standard treatment.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Evidence-Based Medicine; Humans; Mitral Valve Stenosis; Randomized Controlled Trials as Topic; Thromboembolism; Treatment Outcome; Vitamin K

Oral anticoagulation therapy is essential in patients with atrial fibrillation and clinicians need guidance on decision-making between the vitamin K antagonists (VKA), e.g. warfarin, or non-vitamin K antagonist oral anticoagulants. Observational studies have shown that patients who receive VKA therapy spend a significant percentage of their time with international normalized ratio values outside of the therapeutic range (time in therapeutic range, TTR <60%.) Recently, a clinical score has been developed with commonly encountered clinical features, the SAMe-TT2R2 score, to help decision-making with regard to whether a patient is likely to do well, or not, with a VKA. Those with a SAMe-TT2R2 score of 0-1 are likely to do well on a VKA, while those with a SAMe-TT2R2 score ≥ 2 are on probability going to achieve suboptimal TTR. In this article, we provide an overview of the main published retrospective and prospective studies that have validated the SAMe-TT2R2 score and its value for decision-making in daily clinical practice.

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; International Normalized Ratio; Vitamin K; Warfarin

Stroke is the most serious clinical consequence of atrial fibrillation, which is the most common cardiac arrhythmia. Non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as efficacious, safe and convenient stroke prevention agents. This updated network meta-analysis focused on the relative efficacy and safety of apixaban compared with dabigatran, rivaroxaban and edoxaban for stroke prevention in (i) patients with CHADS2 score ≥ 2, (ii) secondary stroke prevention, and (iii) patients with high quality anticoagulation control with warfarin.. A fixed-effects network meta-analysis was conducted, including data from four Phase III randomised controlled trials (> 70,000 patients with non-valvular atrial fibrillation). The results of the base-case analysis comparing NOACs with warfarin were broadly in line with the results from the individual trials. Results from the three subgroup analyses were broadly similar to the base case results. For example in patients with CHADS2 score ≥ 2, apixaban, high-dose dabigatran, rivaroxaban, and high-dose edoxaban had significantly lower hazards of stroke/systemic embolism compared with low-dose edoxaban. Apixaban and low-dose edoxaban were associated with significantly lower hazards of major bleeding compared with rivaroxaban and dabigatran 150 mg. However, several treatment comparisons that were significant in the base-case analysis were not significant in the patient subgroups, due to the reduced sample size of the subgroups compared with the overall population.. Among the NOACs, apixaban offered the most favourable efficacy and safety profile in the overall patient population as well as in the three subgroups investigated.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Vitamin K

Topics: Antithrombins; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Orthopedic Procedures; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thrombosis; Vitamin K

Rivaroxaban is increasingly used in patients undergoing catheter ablation of atrial fibrillation (AF). In the absence of large controlled trials, a comprehensive meta-analysis of the literature appears to be the best way to obtain reliable evidence on rare peri-procedural outcomes such as thromboembolic or bleeding events. We aimed to provide a detailed analysis of currently available data on safety and efficacy of peri-procedural rivaroxaban in patients undergoing AF ablation. We performed a systematic search of the English language literature for studies comparing peri-procedural rivaroxaban therapy with vitamin K antagonists (VKAs) and reporting detailed data on bleeding and/or thromboembolic complications. The Peto odds ratio (POR) was used to pool data into a fixed-effect meta-analysis. A total of 7400 patients undergoing catheter ablation were included in 15 observational and 1 randomized studies of which 1994 were receiving rivaroxaban and 5406 VKA. The risk of thromboembolism trended to be lower in the rivaroxaban group [4/1954 vs. 19/5219, POR 0.40, 95% confidence interval (CI), 0.16-1.01, P = 0.052]. Major bleeding events occurred in 23 of 1994 cases (1.15%) in the rivaroxaban and 90 of 5406 (1.66%) in the VKA group (POR 0.74, 95% CI, 0.46-1.21, P = 0.23). A total of 87 minor bleeding events were reported in 1753 patients (4.96%) in the rivaroxaban group and in 165 of 4009 patients (4.12%) in the VKA group (POR 0.84, 95% CI 0.63-1.11, p = 0.22). In patients undergoing AF ablation, rivaroxaban appears to be an effective and safe alternative to VKA.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Catheter Ablation; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin

Anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) is of paramount importance for prevention of thromboembolic events, and recent studies favor uninterrupted vitamin K antagonists (VKAs). We aimed to compare the efficacy and safety of new oral anticoagulants (NOACs) to uninterrupted VKAs for anticoagulation in CA by performing a meta-analysis. PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov databases were searched for studies comparing NOACs with uninterrupted VKAs in patients who underwent CA for AF from January 1, 2000, to August 31, 2015. Odds ratio (OR) and Peto's OR (POR) were used to report for event rates >1% and <1%, respectively. A total of 11,686 patients with AF who underwent CA in 25 studies were included in this analysis. There was no significant difference between NOACs and uninterrupted VKAs in occurrence of stroke or transient ischemic attacks (POR 1.35, 95% CI 0.62 to 2.94) and major bleeding (POR 0.87, 95% CI 0.58 to 1.31), which were consistent in subgroup analysis of interrupted and uninterrupted NOACs. A lower risk of minor bleeding was observed with NOACs (OR 0.80, 95% CI 0.65 to 1.00), and no major differences were observed for the risk of thromboembolic events, cardiac tamponade or pericardial effusion requiring drainage, and groin hematoma. NOACs, whether interrupted preprocedure or not, were associated with equal rates of stroke or TIA and major bleeding complications and less risk of minor bleeding compared with uninterrupted VKAs in CA for AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dabigatran; Factor Xa Inhibitors; Humans; Ischemic Attack, Transient; Observational Studies as Topic; Prothrombin; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Use of uninterrupted vitamin K antagonists (VKAs) during ablation of atrial fibrillation is superior to bridging with heparin. Few studies evaluated the use of uninterrupted new oral anticoagulants (NOACs) during ablation of atrial fibrillation. These studies are relatively small in size and mostly underpowered to show differences in the infrequent thromboembolic complications between comparators.. We performed the first meta-analysis of uninterrupted NOAC compared with uninterrupted VKA in ablation of atrial fibrillation. We searched the online databases until May 2015 and report outcomes of interest as odds ratios (ORs) using a random effects model. A total of 3544 atrial fibrillation patients in 8 studies who underwent catheter ablation were included in this analysis.. Overall, stroke and/or transient ischemic attack events were of very low incidence with uninterrupted anticoagulation strategy in 6 of 3544. There were no differences in rates of stroke and/or transient ischemic attack between uninterrupted NOAC and uninterrupted VKA, 0.11% vs 0.22% (OR, 0.65; 95% confidence interval [CI], 0.14-2.96; P = 0.58), nor in major bleeding 0.9% vs 1% (OR, 0.94; 95% CI, 0.48-1.87; P = 0.87). All bleeding 6.5% vs 7.3% (OR, 0.93; 95% CI, 0.67-1.29; P = 0.65), minor bleeding 6.3% vs 7.1% (OR, 0.93; 95% CI, 0.67-1.28), and cardiac tamponade 0.6% vs 0.6% (OR, 1.0; 95% CI, 0.43-2.31; P = 1.0) were all equal with uninterrupted NOACs compared with uninterrupted VKAs. Among 3544 patients, only one death occurred in the VKA group.. Use of uninterrupted NOACs in ablation appears to be as safe and efficacious as use of uninterrupted VKAs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Evidence-Based Medicine; Humans; Risk Factors; Stroke; Thromboembolism; Vitamin K

The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Drug Monitoring; Educational Status; Europe; Female; Health Care Surveys; Health Knowledge, Attitudes, Practice; Hemorrhage; Humans; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Patient Education as Topic; Patients; Predictive Value of Tests; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Atrial fibrillation (AF) is associated with an increased risk of stroke. AF-related strokes cause greater disability and mortality than those in patients without AF, and are associated with a significant clinical and economic burden in Mexico. Antithrombotic therapy reduces stroke risk in patients with AF and is recommended for all patients except those classified as having a low stroke risk. However, its use is suboptimal all around the world; one study showed that only 4 % of Mexican patients with AF who presented with ischemic stroke were in the therapeutic range for anticoagulation. Vitamin K antagonists (VKAs) such as warfarin or acenocoumarin have long been the only oral anticoagulants for stroke prevention in AF. Although effective, VKAs have disadvantages, including the need for regular coagulation monitoring and dose adjustment. Interactions with numerous common medications and foods contribute to the risk of serious bleeding and thrombotic events in VKA-treated patients. Thus novel oral anticoagulants (NOACs), more properly called direct oral anticoagulants (DOACs), such as dabigatran etexilate, rivaroxaban, apixaban, and edoxaban (not available in Mexico), have been developed. These offer the convenience of fixed-dose treatment without the need for monitoring, and have few drug or food interactions. Pivotal phase III trials have demonstrated that these agents are at least as effective as warfarin in preventing stroke and are associated with a reduced risk of intracranial hemorrhage. With apixaban approved in Mexico in April 2013, clinicians now have the choice of three novel DOACs as alternatives to warfarin. However, it is yet to be established which of these agents should be the first choice, and treatment decisions are likely to depend on the individual patient's characteristics.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Drug Administration Schedule; Drugs, Investigational; Evidence-Based Medicine; Humans; Mexico; Practice Guidelines as Topic; Precision Medicine; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Vitamin K

Several patients with non-valvular atrial fibrillation treated with warfarin or other vitamin-K antagonists (VKA) might benefit from switching to an oral non vitamin-K antagonist anticoagulant (NOAC). In the absence of randomised comparative trials of switching to NOACs versus maintaining VKA treatment, several considerations argue in favour of a switching strategy. First, there is conclusive evidence that haemorrhagic strokes and intracranial bleedings are much fewer in number with NOACs than with warfarin. The risk of intracranial bleeding is 52 % lower with NOACS than with warfarin, with extremes ranging from 33 to 70 %. Such benefit is applicable to different NOACs, and independent of the time-in-therapeutic range under warfarin. Patients at increased risk for intra-cranial bleeding (renal dysfunction, or prior stroke or intra-cranial bleeding) should benefit most from switching to NOACs. Patients with labile International Normalized Ratio are also considered good candidates for switching because of their increased risk of stroke, and the lack of interactions between the effects of NOACs versus warfarin and the time-in-therapeutic range. Furthermore, some NOACs proved to be superior to warfarin in reducing the risk of thromboembolic complications even in intention-to-treat analyses. As further advantage, NOACs show fewer drug-drug and drug-food interactions when compared with warfarin. Last, but not least, NOACs do not need frequent blood drawings except in patients with moderate renal dysfunction, in whom periodic controls of serum creatinine are generally advised. The higher cost remains a barrier to a wider use of NOACs, especially in low-income settings.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Evidence-Based Medicine; Female; Humans; Intracranial Hemorrhages; Male; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Severity of Illness Index; Survival Rate; Treatment Outcome; Vitamin K; Warfarin

Ischaemic strokes resulting from atrial fibrillation (AF) constitute a devastating condition for patients and their carers with huge burden on health care systems. Prophylactic treatment against systemic embolization and ischaemic strokes is the cornerstone for the management of AF. Effective stroke prevention requires the use of the vitamin K antagonists or non-vitamin K oral anticoagulants (NOACs). This article summarises the latest developments in the field of stroke prevention in AF and aims to assist physicians with the choice of oral anticoagulant for patients with non-valvular AF with different risk factor profile.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient-related and procedure-related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non-valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aortic Valve; Atrial Fibrillation; Elective Surgical Procedures; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Perioperative Care; Phenprocoumon; Prothrombin; Randomized Controlled Trials as Topic; Societies, Medical; Thromboembolism; Thrombosis; United States; Vitamin K; Warfarin

The aim of this network meta-analysis was to evaluate the comparative efficacy and safety of dabigatran, rivaroxaban, apixaban, interrupted vitamin K antagonist (I-VKA), and continuous VKA (C-VKA) in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF).. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify clinical trials comparing dabigatran, rivaroxaban, or apixaban with I-VKA or C-VKA, or against each other, in AF patients undergoing RFCA. A network meta-analysis was conducted to directly and indirectly compare the efficacy and safety of competitive anticoagulation regimens with a Bayesian random-effects model.. A total of 39 studies enrolling 27,766 patients were included. C-VKA demonstrated significant superiority over I-VKA in reducing thromboembolic events (risk difference [RD] -0.0068, 95 % confidence interval [CI] -0.0106 to -0.0032) and major bleeding complications (RD -0.0044, 95 % CI -0.0098 to -0.0006). Rivaroxaban compared with I-VKA was associated with a lower risk of thromboembolism (RD -0.0073, 95 % CI -0.0134 to -0.0012), being at the best ranking position among all of the compared anticoagulation regimens in terms of both the efficacy and safety. None of the remaining comparisons reached statistically significant difference in the rate of thromboembolism or major bleeding.. The present study suggests that C-VKA is superior to I-VKA for AF patients undergoing RFCA. Rivaroxaban is the highest probability to be the optimal alternative to C-VKA among the three non-VKA oral anticoagulants in AF ablation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Causality; Comorbidity; Dabigatran; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thromboembolism; Treatment Outcome; Vitamin K

Appropriate activated clotting time (ACT) during catheter ablation of atrial fibrillation (CA-AF) is essential to minimize periprocedural complications.. An electronic search was performed using major databases. Outcomes were thromboembolic (TE) and bleeding complications according to ACT levels (seconds). Heparin dose (U/kg) and time (minutes) to achieve the target ACT was compared among patients receiving vitamin K antagonist (VKA) versus non-VKA oral anticoagulants (NOAC). Nineteen studies involving 7,150 patients were identified. Patients with ACT > 300 had less TE (OR, 0.51; 95% CI 0.35-0.74) and bleeding (OR, 0.70; 95% CI 0.60-0.83) compared to ACT < 300, when using any type of oral anticoagulation. The use of VKA was associated with reduced heparin requirements (mean dose: 157 U/kg vs. 209 U/kg, P < 0.03; SDM -0.86 [95% CI -1.39 to -0.33]), and with lower time to achieve the target ACT (mean time: 24 minutes vs. 49 minutes, P < 0.03; SDM -11.02 [95% CI -13.29 to -8.75]) compared to NOACs. No significant publication bias was found.. Performing CA-AF with a target ACT > 300 decreases the risk of TE without increasing the risk of bleeding. Patients receiving VKAs required less heparin and reached the target ACT faster compared to NOACs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Catheter Ablation; Chi-Square Distribution; Drug Administration Schedule; Hemorrhage; Heparin; Humans; Odds Ratio; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K

Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature.

Topics: Age Factors; Anticoagulants; Antithrombins; Arthroplasty, Replacement; Atrial Fibrillation; Comorbidity; Critical Illness; Drug Interactions; Drug Monitoring; Hemorrhage; Heparin; Humans; Neoplasms; Perioperative Care; Pulmonary Embolism; Stroke; Venous Thromboembolism; Vitamin K

Aim of our study was to assess the safety and efficacy on factor-Xa inhibitors (FXIs) in patients with non-valvular atrial fibrillation (NVAF) as compared to Vitamin K antagonist (VKA).. Phase II and III randomized controlled trials that reported clinical safety and efficacy of FXI in patients with NVAF were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through December 10, 2015. The primary safety outcome of our study was composite of stroke and systemic embolic event. Secondary outcomes studied were individual endpoints of primary safety outcome, major bleeding, clinically relevant non-major bleed (CRNMB), and all-cause mortality.. We included 11 RCTs with a total of 59,164 participants, of which 34,231 patients received oral FXI and 24,933 patients were on VKA with a mean follow-up of 369days. There was a significant reduction in primary outcome with FXI compared to VKA, 1,112 (3.4%) versus 816 (3.6%) events, respectively (OR 0.82; 95% CI 0.68-0.99). Use of FXI significantly reduced major bleeding events compared to VKA, OR 0.74, 95% CI 0.58-0.96, test for heterogeneity (I(2)=74%). Incidence of CRNMB was not different between FXI and VKA groups, OR 0.84, 95% CI 0.68-1.04. There was a significant reduction in all-cause mortality in FXI group compared to VKA group, OR 0.88, 95% CI 0.83-0.94 with no significant heterogeneity.. Use of FXI was associated with a significant reduction in major bleeding events and all-cause mortality without increased risk of stroke or SEE compared to VKA.

Topics: Administration, Oral; Atrial Fibrillation; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K

Antithrombotic management of outpatients with stable coronary artery disease (CAD) who also have an indication for long-term oral anticoagulation (OAC) is critical in daily practice, firstly because these patients are frequently seen, and secondly because they have shown a high risk of both ischemic events and bleeding as compared to patients without OAC. The current guidelines recommend that most of such patients should be treated with OAC alone (without any antiplatelet therapy) after 12 months of stability even when a stent has been implanted. Robust data are however very sparse and level of evidence very low to support such a strategy. The goal of the present manuscript is to review all available evidences to help the physician's choices in this specific context and to highlight the unsolved issues that should be addressed by new studies in the near future.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Humans; Outpatients; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Vitamin K

Emerging observational studies using propensity score (PS) methods assessed real-world comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with non-valvular atrial fibrillation (AF). We aimed to compare treatment effect estimates of NOACs between PS studies and randomized controlled trials (RCTs). Electronic databases and conference proceedings were searched systematically. Primary outcomes included stroke or systemic embolism (SE) and major bleeding. A random-effects meta-analysis was performed to synthesize the data by pooling the PS- and RCT-derived hazard ratios (HRs) separately. The ratio of HRs (RHR) from the ratio of PS-derived HRs relative to RCT-derived HRs was used to determine whether there was a difference between estimates from PS studies and RCTs. There were 10 PS studies and 5 RCTs included for analysis. No significant difference of treatment effect estimates between the PS studies and RCTs was observed: RHR 1.11, 95 % CI 0.98-1.23 for stroke or SE; RHR 1.07, 95 % CI 0.87-1.34 for major bleeding. A significant association between NOACs and risk of stroke or SE was observed: HR 0.88, 95 % CI 0.83-0.94 for the PS studies; HR 0.79, 95 % CI 0.72-0.87 for the RCTs. However, no relationship between NOACs and risk of major bleeding was found: HR 0.91, 95 % CI 0.79-1.05 for the PS studies; HR 0.85, 95 % CI 0.73-1.00 for the RCTs. In this study, treatment effect estimates of NOACs versus warfarin in patients with non-valvular AF from PS studies are found to be in agreement with those from RCTs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Propensity Score; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Vitamin K; Warfarin

In the RE-LY clinical trial, dabigatran presented a better effectiveness/safety profile when compared to warfarin. However, clinical trials are not very representative of the real-world setting. We aimed to assess the performance of dabigatran in real-world patients with atrial fibrillation (AF) by means of a systematic review and meta-analysis of observational comparison studies with vitamin K antagonists (VKA). We searched PubMed, Embase and Scopus databases until November 2015 and selected studies according to the following criteria: observational study performed with nonvalvular AF patients; reporting adjusted hazard ratios (HR) of clinical events in a follow-up period; for dabigatran 75 mg, 110 mg or 150 mg versus VKA. Twenty studies were selected which included 711,298 patients, 210,279 of which were treated with dabigatran and the remaining 501,019 with VKA. Ischaemic stroke incidence was of 1.65 /100 patient-years for dabigatran and 2.85/100 patient-years for VKA (HR 0.86, 95 % confidence interval of 0.74-0.99). Major bleeding rate was 3.93/100 patient-years for dabigatran and 5.61/100 patient-years for VKA (0.79, 0.69-0.89). Risk of mortality (0.73, 0.61-0.87) and intracranial bleeding (0.45, 0.38-0.52) were significantly lower in patients treated with dabigatran when compared to patients on VKA. Risk of gastrointestinal (GI) bleeding was significantly higher in patients treated with dabigatran (1.13, 1.00-1.28). No significant difference was observed in risk of myocardial infarction (0.99, 0.89-1.11). In this combined analysis of real-world observational comparison studies with VKA, dabigatran was associated with a lower risk of ischaemic stroke, major bleeding, intracranial bleeding and mortality, higher risk of GI bleeding and a similar risk of myocardial infarction.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Observational Studies as Topic; Stroke; Vitamin K

Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Overall prevalence is estimated to 5.5% and the incidence increases with age. As the population ages, the prevalence and costs of AF are expected to increase. AF is the most important cause of stroke in patients >75years. Until recently, Vitamin K antagonists (VKAs) were the only available oral anticoagulants (OACs) evaluated for long-term treatment of patients with AF with or without coronary heart disease (CHD). This situation was challenged by introduction of non-VKA oral anticoagulants (NOACs). In AF, use of NOACs seems to be as effective and safe as VKAs, especially in elderly patients. AF and CHD are frequently associated and the question of antithrombotic management in aging patients is delicate. In elderly patients experiencing a new AF episode after an acute coronary syndrome, triple antithrombotic therapy should be as short as possible in order to decrease the risk of major bleedings. To date, there is no specific study or available guidelines regarding the NOACs use specifically in elderly patients experiencing both AF and CHD. In this review, we try to provide a perspective on NOACs future incorporation into clinical practice in elderly patients with both AF and CHD.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Disease; Humans; Stroke; Vitamin K

Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating. Most could be prevented if efforts were directed towards detection of atrial fibrillation before stroke occurs, through screening or case finding, and treatment of all patients with atrial fibrillation at increased risk of stroke with well-controlled vitamin K antagonists or non-vitamin K antagonist anticoagulants. The default strategy should be to offer anticoagulant thromboprophylaxis to all patients with atrial fibrillation unless defined as truly low risk by simple validated risk scores, such as CHA2DS2-VASc. Assessment of bleeding risk using the HAS-BLED score should focus attention on reversible bleeding risk factors. Finally, patients need support from physicians and various other sources to start anticoagulant treatment and to ensure adherence to and persistence with treatment in the long term.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Medication Adherence; Registries; Risk Assessment; Risk Factors; Stroke; Vitamin K; Warfarin

Many patients with atrial fibrillation have substantial symptoms despite ventricular rate control and require restoration of sinus rhythm to improve their quality of life. Acute restoration (ie, cardioversion) and maintenance of sinus rhythm in patients with atrial fibrillation are referred to as rhythm control. The decision to pursue rhythm control is based on symptoms, the type of atrial fibrillation (paroxysmal, persistent, or long-standing persistent), patient comorbidities, general health status, and anticoagulation status. Many patients have recurrent atrial fibrillation and require further intervention to maintain long term sinus rhythm. Antiarrhythmic drug therapy is generally recommended as a first-line therapy and drug selection is on the basis of the presence or absence of structural heart disease or heart failure, electrocardiographical variables, renal function, and other comorbidities. In patients who continue to have recurrent atrial fibrillation despite medical therapy, catheter ablation has been shown to substantially reduce recurrent atrial fibrillation, decrease symptoms, and improve quality of life, although recurrence is common despite continued advancement in ablation techniques.

Topics: Administration, Oral; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Electric Countershock; Heart Failure; Heart Rate; Humans; Practice Guidelines as Topic; Quality of Life; Stroke; Thromboembolism; Time Factors; Vitamin K

Atrial fibrillation (AF) is a common cardiac rhythm disturbance and is associated with a 5-fold increased risk of stroke. The most important risk factors for stroke in patients with AF are previous stroke and age ≥ 75 years. Canadian guidelines recommend anticoagulant therapy for patients with AF who are older than the age of 65 years, but the elderly often remain undertreated, primarily because of concerns regarding bleeding. Non-vitamin K oral anticoagulants appear to be safer, at least as efficacious, and more convenient than warfarin, and are a cost-effective alternative for elderly patients with AF. We review the evidence for the use of antithrombotic agents for stroke prevention in elderly patients (age ≥ 75 years) with nonvalvular AF.

Topics: Accidental Falls; Aged; Anticoagulants; Atrial Fibrillation; Cognitive Dysfunction; Coronary Artery Disease; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Polypharmacy; Renal Insufficiency; Risk Assessment; Stroke; Vitamin K

The safety of dabigatran versus adjusted-dose vitamin K antagonist (VKA) treatment is the subject of debate. We evaluated the risk of myocardial infarction (MI) or mortality in patients with atrial fibrillation (AF) treated in clinical practice with dabigatran or a VKA. We performed a meta-analysis of observational studies that included an adjusted or matched analysis and reported MI, or death in AF patients treated with dabigatran or a VKA. Ten published analyses met the inclusion criteria. Of the 539,559 patients, 17,365 (3 %) patients were on dabigatran 110 mg twice daily (bid), 150,948 (28 %) were on dabigatran 150 mg bid, and 371,246 (69 %) were on VKA. Adjusted risk for MI versus VKA was 0.71 (0.47-1.07; p=0.10) in patients starting oral anticoagulant (OAC) treatment with dabigatran 110 mg, 0.82 (0.71-0.96; p=0.01) in patients starting dabigatran 150 mg, 1.40 (1.04-1.88; p=0.03) in patients switching OAC treatment to dabigatran 110 mg, and 1.28 (0.88-1.87; p=0.19) in patients switching OAC treatment to dabigatran 150 mg, with statistical homogeneity in each subgroup. Risk of death was consistently lower in patients treated with dabigatran 110 mg (HR 0.79; 0.65-0.96; p=0.02) or 150 mg (HR 0.65; 0.57-0.73; p<0.00001) versus VKA. In conclusion, dabigatran use, as currently prescribed in routine practice for AF patients, was associated with a lower risk of MI in OAC-naïve patients treated with dabigatran 150 mg compared with VKA, and a higher risk of MI in patients switching from VKA to dabigatran 110 mg. Risk of death was lower in AF patients treated with either dose of dabigatran versus VKA.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Myocardial Infarction; Observational Studies as Topic; Risk Assessment; Vitamin K

For more than 50 years, vitamin K antagonists (VKAs) have been the standard of care for treatment of atrial fibrillation (AF). However, the numerous limitations of VKAs have led to the development of non-VKA oral anticoagulants (NOACs). There are 4 NOACs currently approved for prevention of thromboembolism in patients with nonvalvular AF. This article provides an overview of AF, summarizes basic properties of NOACs, and reviews the landmark trials. Current data on use of NOACs in special populations and specific clinical scenarios are also presented. Lastly, recommendations from experts on controversial topics of bleeding management and reversal are described.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Thromboembolism; Vitamin K

Direct oral anticoagulants (DOACs) have been approved for the treatment of venous thromboembolism and atrial fibrillation based on randomized controlled trials (RCTs) of direct comparisons with vitamin K antagonists. Despite having more than 100,000 patients enrolled, safety and efficacy are debated in selected populations. Although DOACs are reviewed as a class of anticoagulant, pharmacokinetic differences exist such that different medications may be beneficial in distinct clinical settings. Synthesizing available evidence based on phase III RCTs, post hoc subgroup analyses, and pooled metaanalyses, this review provides an overview of DOACs and scrutinizes individual differences in their applications for the special populations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Venous Thromboembolism; Vitamin K

A bidirectional relationship exists between atrial fibrillation (AF) and chronic renal disease. Patients with AF have a higher incidence of renal dysfunction, and the latter predisposes to incident AF. The coexistence of both conditions results in a higher risk for thromboembolic-related adverse events but a paradoxical increased hemorrhagic risk. Oral anticoagulants (both vitamin K antagonists [VKAs] and non-VKA oral anticoagulants [NOACs]) have been demonstrated to be effective in mild to moderate renal dysfunction. Patients with severe renal impairment were excluded from the non-VKA oral anticoagulant trials, so limited data are available. In end-stage renal failure, the net clinical benefit of VKAs in dialysis-dependent patients remains uncertain, although some evidence suggests that such patients may do well with high-quality anticoagulation control. Risk stratification and careful follow-up of such patients are necessary to ensure a net clinical benefit from thromboprophylaxis.

Topics: Administration, Oral; Algorithms; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Renal Insufficiency, Chronic; Risk Assessment; Stroke; Thromboembolism; Vitamin K

The high risk of both stroke and major bleeding in atrial fibrillation (AF) patients with chronic kidney disease (CKD) defines an important population for whom the assessment of the balance between the risk of ischemic stroke and of bleeding is essential. The use of novel oral anticoagulants (NOACs) may be a viable option in this population due to their greater net clinical benefit than warfarin, as demonstrated by the results of the clinical phase III trials. NOACs have been found to have a greater net clinical benefit than warfarin in patients at high risk of either stroke (CHADS2≥1 or CHA2DS2-VASc score≥2) or bleeding (HAS-BLED≥3). Noteworthy, it has been found also a positive net clinical benefit with apixaban and dabigatran 110mg BID in patients with CHADS2 score=0 and HAS-BLED score≥3. At CHA2DS2-VASc score=1, apixaban and both doses of dabigatran were superior to warfarin in terms of the net clinical benefit. Available scientific evidence might help in clinical decision-making regarding the use of NOACs in patients with CKD who are at high risk for both stroke and bleeding. Overall, current findings provide a rationale for the choice of apixaban or rivaroxaban over dabigatran in patients with AF and stage III CKD. Out of the NOACs, only apixaban has been recently approved for the use in patients with end-stage renal dysfunction on hemodialysis (the recommended dose of 5mg twice daily should be halved in patients with body weight of ≤60kg and or age≥80years).

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Outcome; Vitamin K

Anticoagulant treatment is required for the treatment and prevention of thromboembolic disorders. Vitamin K antagonists are commonly used oral anticoagulants worldwide. Acenocoumarol is mono-coumarin derivative with racemic mixture of R (+) and S (-) enantiomers. Efficacy and safety of acenocoumarol has been evaluated in atrial fibrillation, cardiac valve replacement, after myocardial infarction, treatment of deep vein thrombosis, after major surgeries and after critical illness requiring prolonged hospitalization. Acenocoumarol is effective and safe in all age groups. It offers an advantage over warfarin in terms of better stability of anti-coagulant effect. Due to its economic advantage acenocoumarol may be suitable oral anticoagulant for long term use in countries like India.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; India; Mixed Function Oxygenases; Myocardial Infarction; Thromboembolism; Treatment Outcome; Vitamin K

Data regarding the clinical outcomes in patients with atrial fibrillation (AF) receiving dual antiplatelet therapy (DAPT) and an anticoagulant in addition to DAPT (DAPT + vitamin K antagonist [VKA]) after coronary stent implantation are still controversial. Therefore, in order to solve this issue, we aim to compare the adverse clinical outcomes in AF patients receiving DAPT and DAPT + VKA after percutaneous coronary intervention and stenting (PCI-S).. Observational studies comparing the adverse clinical outcomes such as major bleeding, major adverse cardiovascular events, stroke, myocardial infarction, all-cause mortality, and stent thrombosis (ST) in AF patients receiving DAPT + VKA therapy, and DAPT after PCI-S have been searched from Medline, EMBASE, and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on discontinuous variables, and the pooled analyses were performed with RevMan 5.3.. Eighteen studies consisting of a total of 20,456 patients with AF (7203 patients received DAPT + VKA and 13,253 patients received DAPT after PCI-S) were included in this meta-analysis. At a mean follow-up period of 15 months, the risk of major bleeding was significantly higher in DAPT + VKA group, with OR 0.62 (95% CI 0.50-0.77, P < 0.0001). There was no significant differences in myocardial infarction and major adverse cardiovascular event between DAPT + VKA and DAPT, with OR 1.27 (95% CI 0.92-1.77, P = 0.15) and OR 1.17 (95% CI 0.99-1.39, P = 0.07), respectively. However, the ST, stroke, and all-cause mortality were significantly lower in the DAPT + VKA group, with OR 1.98 (95% CI 1.03-3.81, P = 0.04), 1.59 (95% CI 1.08-2.34, P = 0.02), and 1.41 (95% CI 1.03-1.94, P = 0.03), respectively.. At a mean follow-up period of 15 months, DAPT + VKA was associated with significantly lower risk of stroke, ST, and all-cause mortality in AF patients after PCI-S compared with DAPT group. However, the risk of major bleeding was significantly higher in the DAPT + VKA group.

Topics: Anticoagulants; Atrial Fibrillation; Blood Vessel Prosthesis Implantation; Coronary Disease; Drug Therapy, Combination; Humans; Observational Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stents; Vitamin K

To investigate the relative effect of warfarin versus non-vitamin K oral anticoagulants (NOACs) in thrombotic and bleeding outcomes in subgroups of atrial fibrillation (AF) patients with varying degrees of renal dysfunction.. Systemic review and meta-regression analyses on NOACs versus warfarin, supplemented with indirect comparisons were conducted. The eligibility criteria for inclusion were randomised controlled trials comparing NOACs against warfarin for stroke prevention in AF patients. Outcomes of interest were stroke or systemic embolism (SE) and major bleeding.. Five studies comprising 72,845 AF patients randomised to either a NOAC or warfarin were included in the meta-regression analysis. A shift in strata from no renal impairment to renal impairment resulted in a non-significant impact on bleeding and stroke/SE, indicating similar safety and efficacy, despite renal function status. Apixaban was associated with less major bleeding compared to dabigatran and rivaroxaban but not edoxaban in patients with moderate renal impairment. For efficacy outcomes, only dabigatran 150 mg was statistically significantly favoured compared to edoxaban 30 mg. For efficacy outcomes in mild renal impairment, both dabigatran 150 mg and rivaroxaban 10 mg (J-ROCKET) were statistically significantly favoured against edoxaban 30 mg.. Non-vitamin K oral anticoagulants had similar efficacy and safety compared to warfarin across different levels of renal function. Indirect comparisons suggest that apixaban and edoxaban were associated with a better safety profile in patients with moderate renal impairment. However, caution is warranted when interpreting indirect comparisons of drugs investigated in different trials. Prescribers should fit the most appropriate NOAC to the AF patient characteristics (and vice versa) to individualise effective stroke prevention.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency; Stroke; Treatment Outcome; Vitamin K; Warfarin

Atrial fibrillation (AF) confers increased risk of stroke and other thromboembolic events, and oral anticoagulation therefore is the essential part of AF management to reduce the risk of these complications. Until recently, the vitamin K antagonists (VKAs, e.g., warfarin) were the only oral anticoagulants available, acting by decreased synthesis of vitamin K-dependent coagulation factors (II, VI, IX, and X). The VKAs had many limitations: delayed onset and prolonged offset of action, variability of anticoagulant effect among patients, multiple food and drug interactions affecting pharmacological properties of warfarin, narrow therapeutic window, and obligatory regular laboratory control, which all made warfarin "inconvenient" both for patients and clinicians. The limitations of VKAs led to development of a new class of drugs collectively defined as non-VKA oral anticoagulants (NOACs), which included direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban). The NOACs avoid many of the VKA drawbacks. In this review, we will focus on the current evidence justifying the use of NOACs in non-valvular AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) have changed the landscape for stroke prevention in atrial fibrillation (AF). Given the huge burden of AF in Asians, more attention to stroke prevention is clearly needed. Aiming to provide an overview and reappraisal of stroke prevention in Asians with AF, we searched MEDLINE for information on NOACs in Asians. In addition, abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. In the 4 recent Phase 3 trials comparing NOACs to warfarin, a consistent pattern is evident. For efficacy endpoints in the comparison of NOACs vs warfarin, a significant reduction in stroke/systemic embolization was seen for dabigatran 150mg [HR 0.45 (0.28-0.72)], with non-significant trends seen for lower stroke/systemic embolization with other NOACs, except edoxaban 30mg. A similar pattern was seen for ischaemic stroke, with a significant reduction for dabigatran 150mg [HR 0.55 (0.32-0.950]. For haemorrhagic stroke, all NOAC regimes, except rivaroxaban 20mg, had significantly lower hazard ratios. No evidence of increased myocardial infarction was found for NOACs. All-cause mortality was significantly lowered amongst Asian patients on edoxaban 60mg compared to warfarin [HR 0.63 (0.40-0.98)] with non-significant trends to lower mortality with dabigatran 150mg, rivaroxaban and edoxaban 30mg. For safety endpoints, all the NOAC regimes, except rivaroxaban 20mg, significantly reduced major bleeding and 'all bleeding' events. Intracranial haemorrhage was consistently lowered by all NOACs. None of NOACs increased gastrointestinal bleeding. These information suggested that NOACs should be preferentially indicated for stroke prevention in Asians with AF.

Topics: Administration, Oral; Anticoagulants; Asian People; Atrial Fibrillation; Global Health; Humans; Incidence; Stroke; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOAC) have been developed as alternatives to warfarin. Until recently, the latter was the standard oral anticoagulant for patients with non-valvular atrial fibrillation (NVAF). The efficacy and safety of NOAC in Japanese patients with NVAF has been investigated in small trials or subgroups from global randomized control trials (RCT).. We conducted a systematic review and meta-analysis of RCT, to compare the efficacy and safety of NOAC to those of warfarin in Japanese patients with NVAF. Published research was systematically searched for RCT that compared NOAC to warfarin in Japanese patients with NVAF. Random-effects models were used to pool efficacy and safety data across RCT. Three studies, involving 1,940 patients, were identified. Patients randomized to NOAC had a decreased risk for stroke and systemic thromboembolism (relative risk [RR], 0.45; 95% CI: 0.24-0.85), with a non-significant trend for lower major bleeding (RR, 0.66; 95% CI: 0.29-1.47), intracranial bleeding (RR, 0.46; 95% CI: 0.18-1.16) and gastrointestinal bleeding (RR, 0.52; 95% CI: 0.25-1.08).. NOAC are more efficacious than warfarin for the prevention of stroke and systemic embolism in Japanese patients with NVAF. The present findings offer clinicians a more comprehensive picture of NOAC as a therapeutic option to reduce the risk of stroke in Japanese NVAF patients.

Topics: Administration, Oral; Aged; Anticoagulants; Asian People; Atrial Fibrillation; Female; Humans; Japan; Male; Middle Aged; Vitamin K; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are at least non-inferior to Vitamin K Antagonists (VKAs) for stroke prevention on patients with non-valvular atrial fibrillation (AF). We aimed to evaluate the efficacy and safety of NOACs in patients undergoing cardioversion through a systematic review and meta-analysis.. MEDLINE, Cochrane Library, and Web of Science(®) databases (until September 2014) were searched for studies fulfilling inclusion criteria. Two reviewers independently selected randomized controlled trials (RCTs) evaluating NOACs and VKA in patients with AF undergoing cardioversion. The primary outcome was ischemic stroke or systemic embolism (IS/SE). Secondary outcomes were major bleeding, myocardial infarction, and mortality. Risk ratio (RR) and 95 % confidence intervals were derived through random-effects meta-analysis. Heterogeneity was evaluated through I (2) test.. Four RCTs (3 post-hoc analysis) evaluating apixaban, dabigatran, and rivaroxaban in 3,512 patients with AF were included. The risk of IS/SE with NOACs was similar to VKA (RR 0.60, 95 % CI 0.20-1.80; I (2) = 17 %). There was no significant increase in major bleeding (RR 1.27, 95 % CI 0.58-2.81; I (2) = 0 %), myocardial infarction (RR 0.71, 95 % CI 0.10-5.04; I (2) = 0 %), or mortality (RR 0.87, 95 % CI 0.24-3.08; I (2) = 0 %) with NOACs.. This systematic review and meta-analysis suggests that NOACs may be as safe as VKAs in the setting of AF cardioversion.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Causality; Comorbidity; Defibrillators, Implantable; Humans; Incidence; Risk Factors; Stroke; Survival Rate; Treatment Outcome; Vitamin K

The non-vitamin K antagonist oral anticoagulants (NOACs), such as the thrombin inhibitor (dabigatran) and the direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), have been shown to be at least as efficacious and safe as conventional oral anticoagulants, such as the vitamin K antagonists (VKAs) (e.g., warfarin), for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Each NOAC has various advantages and specific features, and therefore decisions regarding appropriate stroke prevention require individual assessment of stroke and bleeding risk on anticoagulation with VKA therapy and NOACs when starting on any of these drugs. This review briefly describes the results of the four NOACs clinical randomized trials and discusses how they might impact clinical practice and choice of anticoagulants in atrial fibrillation patients. Moreover, this review discusses the differences of the proposed management of antithrombotic therapy in several international guidelines and pragmatic issues of NOACs for stroke prophylaxis.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and is a growing health problem that is associated with a significantly increased risk of stroke and thromboembolism. Oral anticoagulant (OAC) therapy reduces the risk of stroke and all-cause mortality in patients with AF. OAC therapy is commonly given as a well-controlled vitamin K antagonist (VKA; e.g. warfarin) and can reduce the risk of stroke in AF patients by almost two-thirds. However, the widespread use of VKAs has been hampered by the unpredictable pharmacokinetic and pharmacodynamic properties of the drugs and justifiable concerns about the consequent risk of haemorrhage. The non-VKA OACs (NOACs) have revolutionized thromboprophylaxis in AF by providing therapeutic options with predictable pharmacodynamic and pharmacokinetic properties that are as efficacious as warfarin in the prevention of stroke and thromboembolism but are more convenient to use. In this review, we provide a patient-centred framework to assist clinicians in recommending the right OAC therapy to fit the individual patient with AF, including methods for stratifying the risk of stroke and haemorrhage and the chances of achieving tight control of VKA anticoagulation, and we discuss the properties of the NOACs that favour their use in particular patient cohorts.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Patient-Centered Care; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Vitamin K; Warfarin

DOACs are increasingly used in patients with NVAF. Information on efficacy and safety of these compounds in patients undergoing electrical or pharmacological cardioversion is limited. Thus, we performed a systematic review and a meta-analysis of the literature to address this issue.. Randomized controlled trials comparing the efficacy and safety of DOACs and VKAs in patients with NVAF were systematically searched in Medline, Web of Science, Scopus, Cochrane, and EMBASE databases (up to September 2014). Pooled relative risk (RR) and the corresponding 95% confidence interval (CI) were calculated for each outcome.. Four randomized controlled trials (3635 patients), for a total of 4517 cardioversions (2869 with DOACs and 1648 with VKAs), were included in the analysis. DOACs and VKAs appeared equally effective in the prevention of stroke/systemic embolism (0.41% vs 0.61%; RR: 0.73, 95% CI: 0.31, 1.72; P=0.48) and of post-cardiovascular death (0.52% vs 0.81%; RR: 0.73, 95% CI: 0.27, 2.03; P=0.55), with a similar risk of major bleeding complications (0.81% vs 0.60%; RR: 1.23, 95% CI: 0.55, 2.71). Heterogeneity among studies was generally absent. Furthermore, the Weighted Mean Incidence (WMI) of complications appeared very low in patients randomized to DOACs (WMI: 0.6% and 0.9% for stroke/systemic embolism and major bleeding, respectively).. Our results suggest that DOACs are at least as effective and safe as VKAs in patients with NVAF undergoing to an electrical or pharmacological cardioversion. Thus, DOACs may be considered a valid and practical alternative to VKAs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Humans; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Scarce data are available about efficacy and safety of new oral anticoagulants (NOACs) for cardioversion (CV) of atrial fibrillation (AF). We performed a meta-analysis of data from randomized studies reporting outcomes of patients receiving NOACs, as compared to vitamin K antagonists (VKAs), and undergoing CV of AF.. Data from four studies were selected, including 4268 CVs. The primary endpoints were the incidence of stroke or systemic embolism and the incidence of major bleeding within 30 days.. There was not any significant difference in the incidence of stroke or systemic embolism between NOACs and VKAs (RR 0.73, p = 0.47) nor in the incidence of major bleeding (RR 1.39, p = 0.13).. We found no evidence of differential outcomes after CV of AF according to treatment with NOACs or VKAs. This finding warrants confirmation in larger clinical series and in the setting of properly powered randomized trials of newly diagnosed AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Atrial fibrillation (AF) is the most commonly observed rhythm disorder in clinical practice. It is associated with a high risk of thromboembolic stroke and increased cardiovascular mortality. Vitamin K antagonists (VKAs), the only oral anticoagulants used for thromboembolic prophylaxis in AF patients over the past 60 years, have been effective in reducing thromboembolic stroke, compared with placebo and aspirin, in this group of patients. However, VKAs have a very narrow therapeutic window, so regular monitoring of the therapeutic effect is obligatory for their use. The need for regular assessment of blood anticoagulation often causes dissatisfaction and reduces patients' quality of life. Non-VKA oral anticoagulants (NOACs), such as dabigatran, a direct thrombin inhibitor, and 3 factor Xa inhibitors, namely rivaroxaban, apixaban, and edoxaban, have been developed in recent years and have increased the armamentarium available to the physician for thromboprophylaxis in non-valvular AF (NVAF) patients. This review describes the characteristics of NOACs, analyzing aspects related to their use in the thromboprophylaxis of NVAF patients. It also discusses how to optimize NOAC therapy in specific clinical conditions, such as renal or liver impairment, and concomitant assumption of drugs potentially interfering with NOACs action. Finally, it focuses on NOAC-related bleeding management in the setting of non-cardiac surgery or radiofrequency catheter ablation of NVAF.

Topics: Administration, Oral; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Stroke; Thromboembolism; Vitamin K

Anticoagulation in cardioversion and ablation of atrial fibrillation is imperative for reducing thrombo-embolic events. Ample information is available about the use of warfarin and vitamin K antagonists (VKA) but few trials examine safety and efficacy of rivaroxaban in these procedures. We aim to explore the hypothesis that rivaroxaban causes equal thrombo-embolic and bleeding events when used in atrial fibrillation patients undergoing ablation or cardioversion compared to VKA.. We searched the online databases as well as conference abstracts till December 2014 for studies comparing rivaroxaban with VKA in atrial fibrillation patients undergoing catheter ablation or cardioversion. We report events as Odds ratio using random effects model except when event rates were less than 1% we used Peto Odds Ratio.. A total of 8872 atrial fibrillation patients in 15 studies undergoing either catheter ablation or cardioversion were included in this analysis. There were significantly lower stroke events with rivaroxaban compared with VKA (Peto Odds Ratio (POR) 0.33, 95% confidence interval (CI) [0.11, 0.95]; P=0.04), and significantly less thrombo-embolic events with rivaroxaban compared with VKA (POR 0.46, 95% CI [0.21, 0.97]; P=0.04). Major and minor bleeding were equal with rivaroxaban versus VKA (Odds Ratio (OR) 0.92, 95% CI [0.62, 1.36]; P=0.68) and (OR 0.81,95% CI [0.58, 1.11]; P=0.19) respectively.. The use of rivaroxaban in ablation and cardioversion of atrial fibrillation may be associated with decreased risk of stroke and thromboembolism with equal bleeding risk compared to VKA.

Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Electric Countershock; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Risk; Rivaroxaban; Stroke; Thromboembolism; Vitamin K

Use of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.. To perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.. Studies were searched for in PubMed and Google Scholar databases.. Studies were considered eligible if: they evaluated the clinical impact of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during periprocedural phase of RFCA; they reported clinical outcome data.. 25 studies were selected, including 9881 cases. The summary measure used was the risk ratio (RR) with 95% confidence interval (CI). The random-effects or the fixed effect model were used to synthesize results from the selected studies.. There was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).. As with every meta-analysis, no patients-level data were available.. The use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events.

Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Hemorrhage; Humans; Incidence; Stroke; Thromboembolism; Vitamin K

Atrial fibrillation (AF) is a significant problem for the aging population and remains a major factor underlying stroke risk. Warfarin anticoagulation has been proven effective for stroke prevention in AF, but can be difficult to manage and requires frequent monitoring. The non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to be as effective as warfarin for stroke prevention in nonvalvular AF (NVAF) and are associated with a reduced risk of bleeding compared with warfarin. Dabigatran, rivaroxaban, apixaban, and edoxaban have been approved in the USA for reducing the risk of stroke in patients with NVAF. In this article, AF risk assessment is discussed and NOAC phase III clinical trials for the prevention of stroke and systemic embolic events are reviewed. Further, differences in stroke and bleeding outcomes between NOACs are highlighted, the use of NOACs for cardioversion and special patient populations is discussed, and management considerations for patients with AF are reviewed.

Topics: Age Factors; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Comorbidity; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Risk Factors; Sex Factors; Stroke; Vitamin K

As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; Clopidogrel; Drug Synergism; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Humans; Mortality; Numbers Needed To Treat; Observational Studies as Topic; Platelet Aggregation Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Risk; Risk Assessment; Stroke; Thiazoles; Thrombophilia; Ticlopidine; Vitamin K

The pharmacological treatment options for anticoagulation in patients with atrial fibrillation (Afib) have increased with the introduction of novel oral anticoagulants, compared with earlier times, when vitamin K antagonist was the drug of choice. As they age, many Afib patients require percutaneous coronary intervention (PCI), necessitating antiplatelet medication in addition to anticoagulation therapy. Choosing the appropriate combination and duration of anticoagulation and antiplatelet therapies may be challenging in stable coronary artery disease (CAD) and even more complicated during and after coronary intervention with the introduction of additional antithrombotic drugs. In this article, we review the scientific basis for the recent guidelines for anticoagulation and antithrombotic therapy in patients with Afib and stable CAD before, during, and after elective PCI.

Topics: Angina, Stable; Anticoagulants; Atrial Fibrillation; Comorbidity; Humans; Percutaneous Coronary Intervention; Risk Factors; Stroke; Vitamin K

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiology; Europe; Evidence-Based Medicine; Guideline Adherence; Humans; Practice Guidelines as Topic; Stroke; Treatment Outcome; Vitamin K

This study was designed to compare efficacy and safety among novel oral anticoagulants (NOACs), which have not been directly compared in randomized control trials to date.. We performed network meta-analyses of randomized control trials in preventing thromboembolic events and major bleeding in patients with atrial fibrillation. PubMed, Embase, and the Cochrane Database of Systematic Reviews for published studies and various registries of clinical trials for unpublished studies were searched for 2002-2013. All phase III randomized controlled trials (RCTs) of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), idraparinux, and ximelagatran were reviewed.. A systematic literature search identified nine phase III RCTs for primary analyses. The efficacy of each NOAC was similar with respect to our primary composite endpoint following adjustment for open label designs [odds ratios (ORs) versus vitamin K antagonists: apixaban 0.79; dabigatran 150mg 0.77; edoxaban 60mg 0.87; rivaroxaban 0.86] except for dabigatran 110mg and edoxaban 30mg. Apixaban and edoxaban 30mg and 60mg had significantly fewer major bleeding events than dabigatran 150mg, ricvaroxaban, and vitamin K antagonists. All NOACs were similar in reducing secondary endpoints with the exception of dabigatran 110mg and 150mg which were associated with a significantly greater incidence of myocardial infarction compared to apixaban, edoxaban 60mg, and rivaroxaban.. Our indirect comparison with adjustment for study design suggests that the efficacy of the examined NOACs is similar across drugs, but that some differences in safety and risk of myocardial infarction exist, and that open label study designs appear to overestimate safety and treatment efficacy. Differences in study design should be taken into account in the interpretation of results from RCTs of NOACs.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Odds Ratio; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiazoles; Thromboembolism; Treatment Outcome; Vitamin K

Strokes, whether ischaemic or haemorrhagic, are the most feared complications of atrial fibrillation (AF) and its treatment. Vitamin K antagonists have been the mainstay of stroke prevention. Recently, direct oral anticoagulants have been introduced. The advantages and disadvantages of these treatment strategies have been extensively discussed. In this narrative review, we discuss dilemmas faced by primary care clinicians in the context of stroke and transient ischaemic attack (TIA) in patients with AF. We discuss the classification of stroke, the different types of stroke seen with AF, the prognosis of AF-related strokes, the early management after AF-related stroke or TIA and the therapeutic options after anticoagulant-associated intracerebral haemorrhage. Most importantly, we aim to dispel common misconceptions on the part of non-stroke specialists that can lead to suboptimal stroke prevention and management.

Topics: Anticoagulants; Atrial Fibrillation; Disease Management; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Prognosis; Stroke; Vitamin K; Warfarin

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia that results from the chaotic depolarization of atrial tissue. AF is the most common sustained cardiac dysrhythmia and the most common dysrhythmia diagnosed in US emergency departments. All patients with AF must have their cardioembolic risk assessed, even if sinus rhythm is restored. Novel oral anticoagulants may be considered instead of vitamin K antagonists for anticoagulation in patients with nonvalvular AF.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Disease Management; Fibrinolytic Agents; Humans; Potassium Channel Blockers; Risk Factors; United States; Vitamin K

Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Atrial Flutter; Benzimidazoles; beta-Alanine; Combined Modality Therapy; Contraindications; Dabigatran; Hemorrhage; Morpholines; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Thiophenes; Thromboembolism; Vitamin K

The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians.. We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model.. Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52-0.83] versus 0.85 [0.77-0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44-0.74] versus 0.89 [0.76-1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19-0.52] versus 0.56 [0.44-0.70], P interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 [0.48-1.32] versus 1.44 [1.12-1.85], P interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding.. Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations.

Topics: Administration, Oral; Anticoagulants; Asian People; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Embolism; Humans; Stroke; Vitamin K

Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear.. To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist).. MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and www.clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism.. Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% (95% CI, 6.53-8.68; I(2) = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I(2) = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years (95% CI, 0.12-0.20; I(2) = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I(2) = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I(2) = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I(2) = 0%).. The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality.

Topics: Adult; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Hemorrhage; Humans; Mortality; Risk; Thromboembolism; Thrombophilia; Treatment Outcome; Vitamin K; Warfarin

Stroke prevention in elderly atrial fibrillation patients remains a challenge. There is a high risk of stroke and systemic thromboembolism but also a high risk of bleeding if anticoagulants are prescribed. The elderly have increased chronic kidney disease, coronary artery disease, polypharmacy, and overall frailty. For all these reasons, anticoagulant use is underutilized in the elderly. In this manuscript, the benefits of non-vitamin K antagonist oral anticoagulants compared with warfarin in the elderly patient population with multiple comorbid conditions are reviewed.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Humans; Risk Factors; Stroke; Vitamin K; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists (VKAs). The aim of this study is to examine the efficacy and safety of NOACs compared with warfarin with composite end points in patients with atrial fibrillation.. This semi-systematic review performed a study of Phase III randomized controlled trials comparing NOACs with vitamin K antagonists (VKAs) in patient with atrial fibrillation using composite end points (combination of various clinical events). The use of composite end points allowed for combining efficacy and safety outcomes, thereby comparing the differences between NOAC and warfarin therapy from a clinical perspective.. Treatment with NOAC compared with warfarin was associated with a significant reduction in the sum of stroke or non-CNS, systemic embolism and major bleeding (odds ratio 0.87; 95% CI: 0.82-0.91).. Generally, NOACs were associated with a more favorable efficacy and safety profile compared with warfarin with regard to composite end points.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Vitamin K; Warfarin

Limited information exists on gender-related differences in the safety and efficacy of non-vitamin K antagonist oral anticoagulants (NOACs).. To assess the safety and efficacy of direct oral anticoagulants (DOACs)/NOACs in men and women pooling data from randomized controlled trials on the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) and on the acute and extended treatment of venous thromboembolism (VTE).. MEDLINE and EMBASE databases were searched up to June 2014. The efficacy outcome was defined as the prevention of stroke and systemic embolism (AF studies), or as the prevention of recurrent VTE or VTE-related death (VTE studies). The safety outcome was defined as the occurrence of major and/or clinically relevant non-major bleeding. Differences in the efficacy and safety outcomes were expressed as risk ratio (RR) with pertinent 95% confidence intervals (95% CI).. A total of 13 studies (> 100,000 patients) were included. DOACs appeared to have a similar efficacy and safety compared with vitamin K antagonists in female and male patients treated for nonvalvular AF and acute VTE. In the extended treatment of VTE NOACs had a RR of bleeding of 4.97 (95% CI 1.06, 23.41) in males and 1.33 (95% CI 0.63, 2.83) in females compared with placebo (subgroup difference chi-square test: 2.25, p = 0.13).. No gender-related difference in the efficacy and safety of NOACs in patients with AF or acute VTE was found. A trend toward an increased risk of bleeding in male patients as compared with female patients was detected in the extended treatment of VTE.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Randomized Controlled Trials as Topic; Sex Characteristics; Venous Thromboembolism; Vitamin K

Millions of US patients are prescribed oral anticoagulants. Traditionally, oral anticoagulation was achieved with vitamin K antagonists (VKAs). In recent years, non-VKA oral anticoagulants (NOACs) have emerged that provide an effective and convenient alternative to VKAs. These agents possess very different pharmacologic properties from what the medical community has grown accustom to with the VKAs. Thus, a new knowledge base is required for NOACs. One particular challenge with the NOACs is the lack of specific reversal agent, resulting in difficulties correcting the coagulopathy induced by these drugs when needed. A review of the current literature is presented to assist clinicians in gaining knowledge of the NOACs to care for patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Risk Factors; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thromboembolism; Vitamin K

Direct oral anticoagulants are now frequently used in patients experiencing atrial fibrillation. Some of these patients may need a cardioversion. How to manage the procedure in these patients? Can we perform the procedure in patients taking the direct oral anticoagulant? Should we switch the treatment to a vitamin K antagonist? When do we need to perform a transesophageal echocardiography? All these questions justify this review article.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Echocardiography, Transesophageal; Electric Countershock; Humans; Practice Guidelines as Topic; Vitamin K

Oral anticoagulation is central to the management of patients with atrial fibrillation (AF) and at least one additional stroke risk factor. For decades, the vitamin K antagonists (e.g. warfarin) remained the only oral anticoagulant available for stroke prevention in AF. The non-vitamin K oral anticoagulants (NOACs) are now available, and these drugs include the direct thrombin inhibitors and factor Xa inhibitors. The latter class includes edoxaban, which has recently been approved for stroke prevention in AF by the United States Food and Drug Administration and the European Medicine Agency. In line with other NOACs, edoxaban avoids the many limitations of warfarin associated with variability of anticoagulation effect and multiple food and drug interactions.. In this review, the currently available evidence on edoxaban in patients with non-valvular AF is discussed. The pharmacology, efficacy and safety, and current aspects of use of edoxaban in patients with non-valvular AF for stroke and thromboembolism prevention are reviewed.. Phase III trials on edoxaban for stroke prevention in non-valvular AF confirms non-inferiority of edoxaban compared to well-managed warfarin both in terms of efficacy and safety. Currently ongoing and future trials as well as real-world data are warranted to confirm its effectiveness and safety for chronic anticoagulation and improve evidence in other areas which are lacking evidence where NOAC use remains controversial.

Topics: Atrial Fibrillation; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Embolism; Factor Xa Inhibitors; Humans; Pyridines; Risk; Stroke; Thiazoles; Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) increases the risk of mortality and stroke. The prevention of these complications is based on oral anticoagulants that are more efficient than salycilates. As compared with antivitamins K agents, new oral anticoagulants are promising for patients presenting non valvular atrial fibrillation because of lower cerebral hemorragic risk (with respect of assessment of renal function and therapeutic compliance). Available studies and recommendations are presented.

Topics: 4-Hydroxycoumarins; Anticoagulants; Atrial Fibrillation; Drugs, Investigational; Humans; Indenes; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Emergencies; Factor Xa Inhibitors; Hemorrhage; Humans; Kidney Diseases; Morpholines; Orthopedic Procedures; Postoperative Complications; Premedication; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

Acute coronary syndrome affects more than 750,000 Americans per year, and antiplatelet agents are the cornerstones of treatment. Atrial fibrillation affects 2.4 million patients in the United States, and venous thromboembolism occurs in 1 to 2 per 1,000 adults per year. Anticoagulants are commonly prescribed to affected patients. Surgeons are commonly called upon to care for patients taking medications that affect normal coagulation. It is important that the surgical community has a fundamental understanding of these agents' pharmacology, which may impact patients' clinical course.. A review of recent literature on pharmacologic agents that affect coagulation was performed.. A number of medications that alter normal coagulation were reviewed in this article including their pharmacologic properties and reversal strategies.. There are a variety of medications that affect a patient's coagulation ability, including many newer agents on the market. This review provides surgeons with the knowledge needed to assist in caring for individuals receiving these drugs.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Thromboembolism; United States; Vitamin K

The use of new oral anticoagulants (NOACs) in patients with impaired renal function has raised major concerns, in particular the possibility of an increased risk of bleeding due to accumulation. The aims of this work were to assess the safety of NOACs in patients with renal failure and describe the relationship between clinical events and drug renal excretion magnitude.. All phase III trials comparing NOACs with vitamin K antagonists (VKAs) in patients with estimated glomerular filtration (eGFR) rate < 50 mL min(-1) were eligible. The main safety and efficacy outcomes were major bleeding and thrombosis. A meta-regression was performed to estimate the correlation between the treatment effect estimate and the percentage of renal excretion.. Nine studies (12 272 patients) were included. A significantly greater relative reduction in major bleeding was seen for NOACs with renal excretion <50% (RR, 0.61; CI, 0.51-0.74) than for those with high renal excretion (RR, 0.96; CI, 0.85-1.07) (interaction test, P < 0.0001). A linear relationship between the relative risk of major bleeding and the magnitude of renal excretion was found by meta-regression (R(2)  = 0.66, P = 0.03). For thrombosis, a greater treatment effect of NOA vs. INR-adjusted VKA was observed in patients with eGFR < 50 mL min(-1) (RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal excretion was found.. New oral anticoagulants were at least as effective as VKAs, with reduced risks of major bleeding and thrombosis in patients with eGFR < 50 mL min(-1) . The renal excretion of these new drugs seemed to modify the safety profile, contrary to the efficacy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Glomerular Filtration Rate; Hemorrhage; Humans; Renal Insufficiency; Thrombosis; Treatment Outcome; Venous Thromboembolism; Vitamin K; Warfarin

Novel oral anticoagulants (NOACs) (rivaroxaban, dabigatran, apixaban) have been approved by international regulatory agencies to treat atrial fibrillation and venous thromboembolism in patients with kidney dysfunction. However, altered metabolism of these drugs in the setting of impaired kidney function may subject patients with CKD to alterations in their efficacy and a higher risk of bleeding. This article examined the efficacy and safety of the NOACs versus vitamin K antagonists (VKAs) for atrial fibrillation and venous thromboembolism in patients with CKD. A systematic review and meta-analyses of randomized controlled trials were conducted to estimate relative risk (RR) with 95% confidence interval (95% CIs) using a random-effects model. MEDLINE, Embase, and the Cochrane Library were searched to identify articles published up to March 2013. We selected published randomized controlled trials of NOACs compared with VKAs of at least 4 weeks' duration that enrolled patients with CKD (defined as creatinine clearance of 30-50 ml/min) and reported data on comparative efficacy and bleeding events. Eight randomized controlled trials were eligible. There was no significant difference in the primary efficacy outcomes of stroke and systemic thromboembolism (four trials, 9693 participants; RR, 0.64 [95% CI, 0.39 to 1.04]) and recurrent thromboembolism or thromboembolism-related death (four trials, 891 participants; RR, 0.97 [95% CI, 0.43 to 2.15]) with NOACs versus VKAs. The risk of major bleeding or the combined endpoint of major bleeding or clinically relevant nonmajor bleeding (primary safety outcome) (eight trials, 10,616 participants; RR 0.89 [95% CI, 0.68 to 1.16]) was similar between the groups. The use of NOACs in select patients with CKD demonstrates efficacy and safety similar to those with VKAs. Proactive postmarketing surveillance and further studies are pivotal to further define the rational use of these agents.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Venous Thromboembolism; Vitamin K

Patients with atrial fibrillation considering use of anticoagulants must balance stroke reduction against bleeding risk. Knowledge of bleeding risk without the use of anticoagulants may help inform this decision.. To determine the rate of major bleeding reported in observational studies of atrial fibrillation patients not receiving Vitamin K antagonists (VKA).. We searched MEDLINE, EMBASE and CINAHL to October 2011 and examined reference lists of eligible studies and related reviews.. All longitudinal cohort studies that included over 100 adult patients with atrial fibrillation not receiving VKA.. Teams of two reviewers independently and in duplicate adjudicated eligibility, assessed risk of bias and abstracted study characteristics and outcomes.. Twenty-one eligible studies included 96,448 patients. Major bleeding rates varied widely, from 0 to 4.69 events per 100 patient-years. The pooled estimate in 13 studies with 78839 patients was 1.59 with a 99% confidence interval of 1.10 to 2.3 and median 1.42 (interquartile range 0.62-2.70). Pooled estimates for fatal bleeding and non-fatal bleeding from 4 studies that reported these outcomes were, respectively, 0.40 (0.34 to 0.46) and 1.18 (0.30 to 4.56) per 100 patient-years. In 9 randomized controlled trials (RCTs) the median rate of major bleeding in patients not receiving either anticoagulant or antiplatelet therapy was 0.6 (interquartile 0.2 to 0.90), and in 12 RCTs the median rate of major bleeding in patients receiving a single antiplatelet agent was 0.75 (interquartile 0.4 to 1.4).. Results suggest that patients with atrial fibrillation not receiving VKA enrolled in observational studies represent a population on average at higher risk of bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk; Vitamin K

Worldwide there is a tremendous need for affordable anticoagulants that do not require monitoring. The advent of the non-warfarin oral anticoagulant drugs represents a major advance for stroke prevention in atrial fibrillation (AF). The objectives of this review are to 1) identify gaps in our current knowledge regarding use of these single target anticoagulant drugs; 2) outline the potential implications of these gaps for clinical practice, and thereby, 3) highlight areas of research to further optimise their use for stroke prevention in AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Humans; Quality Improvement; Stroke; Translational Research, Biomedical; Vitamin K

Anticoagulation is the most-important intervention to prevent stroke in patients with atrial fibrillation (AF). Despite a lower point prevalence of AF in Asian communities and Asian countries than in other populations, individuals of Asian ethnicity are at a disproportionately high risk of stroke and have greater consequent mortality. Warfarin and other vitamin K antagonists are conventionally used for anticoagulation, and demonstrably reduce the risk of stroke and all-cause mortality in patients with AF. The use of warfarin in Asian countries is suboptimal, primarily owing to the universal challenge of achieving controlled anticoagulation with an unpredictable drug as well as concerns about the particularly high-risk of haemorrhage in Asian patients. Instead, antiplatelet therapy has been favoured in Asian communities, this strategy is neither safe nor effective for stroke prevention in these individuals. The non-vitamin K antagonist, oral anticoagulant drugs offer a solution to this challenge. The direct thrombin inhibitor dabigatran, and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have demonstrated noninferiority to warfarin in the prevention of stroke and systemic embolism in international, randomized, controlled trials. Importantly, some of these drugs are also associated with a significantly lower incidence of major haemorrhage, and all result in lower rates of intracranial haemorrhage and haemorrhagic stroke than warfarin. In this article, we review the use of the non-vitamin K antagonist anticoagulants in the management of AF in Asian populations.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Asia; Asian People; Atrial Fibrillation; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Incidence; Prevalence; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

For the prevention of thromboembolic events in patients with atrial fibrillation and a high thrombotic risk, the standard treatment is warfarin, an anticoagulant. Dabigatran, a thrombin inhibitor, is the alternative when warfarin fails to maintain the INR within the therapeutic range. Patients with a moderate thrombotic risk may receive either warfarin or low-dose aspirin. Apixaban, a factor Xa inhibitor anticoagulant, has been authorised in the European Union for use in patients with non-valvular atrial fibrillation and a moderate or high risk of thrombosis. In a double-blind, randomised non-inferiority trial versus warfarin in 18 201 patients, the incidence of stroke or systemic embolism was lower in the apixaban group (average 1.3 versus 1.6 events per 100 patient-years; p = 0.01). This difference was mainly due to a lower incidence of haemorrhagic stroke and did not result in a clear decline in mortality. In addition, these results are undermined by multiple methodological flaws. Clinical evaluation included no trials comparing apixaban with dabigatran; any indirect comparison would be risky given the poor quality of the clinical assessment of both drugs in atrial fibrillation. A double-blind, randomised trial including 5598 patients compared apixaban with aspirin but provided little information on these options in patients with a moderate risk of thrombosis, as most patients were at high risk. In clinical trials, major bleeding events were less frequent with apixaban than with warfarin (average 2.1 versus 3.1 events per 100 patient-years), but they were more frequent with apixaban than with aspirin (1.4 versus 0.9 events per 100 patient-years). In 2013, there is no way of monitoring the anticoagulant activity of apixaban in routine clinical practice, and there is no antidote in case of overdose; the same is true for dabigatran. Apixaban is a substrate for various cytochrome P450 isoenzymes and for P-glycoprotein, creating a risk of multiple drug-drug interactions. In addition, the anticoagulant action of apixaban is increased by renal failure, meaning that renal function must be regularly monitored. In practice, the antithrombotic treatment of choice for patients with atrial fibrillation is warfarin when the risk of thrombosis is high, and warfarin or aspirin when the thrombotic risk is moderate. When the INR cannot be maintained within the desired therapeutic range, it is best to stick with dabigatran.

Topics: Atrial Fibrillation; Clinical Trials as Topic; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Pyrazoles; Pyridones; Vitamin K; Warfarin

Chronic anticoagulation with vitamin K antagonists (VKAs) prevents ischaemic stroke and systemic embolism in people with non-valvular atrial fibrillation (AF) but dose adjustment, coagulation monitoring and bleeding limits its use. Direct thrombin inhibitors (DTIs) are under investigation as potential alternatives.. To assess (1) the comparative efficacy of long-term anticoagulation using DTIs versus VKAs on vascular deaths and ischaemic events in people with non-valvular AF, and (2) the comparative safety of chronic anticoagulation using DTIs versus VKAs on (a) fatal and non-fatal major bleeding events including haemorrhagic strokes, (b) adverse events other than bleeding and ischaemic events that lead to treatment discontinuation and (c) all-cause mortality in people with non-valvular AF.. We searched the Cochrane Stroke Group Trials Register (July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, May 2013), MEDLINE (1950 to July 2013), EMBASE (1980 to October 2013), LILACS (1982 to October 2013) and trials registers (September 2013). We also searched the websites of clinical trials and pharmaceutical companies and handsearched the reference lists of articles and conference proceedings.. Randomised controlled trials (RCTs) comparing DTIs versus VKAs for prevention of stroke and systemic embolism in people with non-valvular AF.. All three review authors independently performed data extraction and assessment of risk of bias. Primary analyses compared all DTIs combined versus warfarin. We performed post hoc analyses excluding ximelagatran because this drug was withdrawn from the market owing to safety concerns.. We included eight studies involving a total of 27,557 participants with non-valvular AF and one or more risk factors for stroke; 26,601 of them were assigned to standard doses groups and included in the primary analysis. The DTIs: dabigatran 110 mg twice daily and 150 mg twice daily (three studies, 12,355 participants), AZD0837 300 mg once per day (two studies, 233 participants) and ximelagatran 36 mg twice per day (three studies, 3726 participants) were compared with the VKA warfarin (10,287 participants). Overall risk of bias and statistical heterogeneity of the studies included were low.The odds of vascular death and ischaemic events were not significantly different between all DTIs and warfarin (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.85 to 1.05). Sensitivity analysis by dose of dabigatran on reduction in ischaemic events and vascular mortality indicated that dabigatran 150 mg twice daily was superior to warfarin although the effect estimate was of borderline statistical significance (OR 0.86, 95% CI 0.75 to 0.99). Sensitivity analyses by other factors did not alter the results. Fatal and non-fatal major bleeding events, including haemorrhagic strokes, were less frequent with the DTIs (OR 0.87, 95% CI 0.78 to 0.97). Adverse events that led to discontinuation of treatment were significantly more frequent with the DTIs (OR 2.18, 95% CI 1.82 to 2.61). All-cause mortality was similar between DTIs and warfarin (OR 0.91, 95% CI 0.83 to 1.01).. DTIs were as efficacious as VKAs for the composite outcome of vascular death and ischaemic events and only the dose of dabigatran 150 mg twice daily was found to be superior to warfarin. DTIs were associated with fewer major haemorrhagic events, including haemorrhagic strokes. Adverse events that led to discontinuation of treatment occurred more frequently with the DTIs. We detected no difference in death from all causes.

Topics: Amidines; Antithrombins; Atrial Fibrillation; Azetidines; Benzimidazoles; Benzylamines; beta-Alanine; Dabigatran; Drug Administration Schedule; Embolism; Female; Humans; Male; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Stroke; Vitamin K; Warfarin

Hypertrophic cardiomyopathy (HCM), which was first described in 1958, occurs in approximately one in 500 people. Patients with HCM are at an increased risk of atrial fibrillation, which is not only poorly tolerated in this population, but also increases their risk of an embolic event. The incidence of stroke in HCM patients with atrial fibrillation is approximately 21-23%. Given the high risk of stroke, antithrombotic therapy with warfarin is recommended in national guidelines. This therapy should be used without regard to other risk factors for stroke that may be present. Anticoagulation with the new oral anticoagulants may be considered as an alternative; although, specific data for patients with HCM is not available. The purpose of this review is to remind practitioners of the importance of stroke prophylaxis with oral anticoagulants in this population.

Topics: Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Humans; Practice Guidelines as Topic; Risk Factors; Stroke; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs), direct inhibitors of thrombin or factor Xa (FXa), are increasingly used in clinical practice for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (NVAF) and for therapy of venous thromboembolism (VTE). Like any anticoagulant treatment, their use is associated with the risk of bleeding events. The first aim of this article is to review the data on bleeding complications from the phase III clinical studies on chronic use of DOACs and from the few available phase IV registers in use of these drugs. In all randomized studies the DOACs showed a statistical non-inferiority for safety versus comparators (in most cases warfarin), although the rates of major bleeding were significantly lower for some DOACs and treatment doses than for warfarin. Data from available phase IV registers confirm that the use of DOACs in clinical practice is not associated with higher bleeding rates versus warfarin. Secondly, we will try to propose a possible treatment of bleeding complications associated with DOACs. Given the absence of specific antidotes, strategies for proper treatment of bleeding events are crucial; however, due to the lack of data, only proposals rather than recommendations are possible.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Hemorrhage; Heparin; Humans; Risk Factors; Severity of Illness Index; Venous Thromboembolism; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Embolism; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Drug Costs; Factor Xa Inhibitors; Humans; Thrombin; Thromboembolism; Vitamin K; Warfarin

In the majority of patients with non-valvular atrial fibrillation (AF) anticoagulation is required to reduce the risk of stroke. Although vitamin K antagonists effectively reduce the risk of stroke, they have many disadvantages that limit their use. Rivaroxaban is a new once-daily oral anticoagulant that overcomes some of these limitations (i.e., no monitoring of anticoagulant effect required and fixed doses can be prescribed). In recent AF studies, rivaroxaban was reported to be at least as effective as warfarin for the prevention of stroke or systemic embolism but with a lesser risk of fatal bleeding and intracranial hemorrhage. More recent data have confirmed the beneficial effects of rivaroxaban, as originally described, and irrespective of the history of previous stroke, heart failure, myocardial infarction, diabetes, moderate renal dysfunction or age. In the present review the authors discuss current evidence regarding the efficacy and safety of rivaroxaban in patients with non-valvular AF.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes; Vitamin K; Warfarin

To aid trialists, systematic reviewers and others, we evaluated the degree of standardisation of control measure reporting that has occurred in atrial fibrillation (AF) and venous thromboembolism (VTE) studies since 2000; and attempted to determine whether the prior recommendation of reporting ≥2 measures per study has been employed.. Systematic review.. We searched bibliographic databases (2000 to June 2013) to identify AF and VTE studies evaluating dose-adjusted vitamin K antagonists (VKAs) and reporting ≥1 control measure. The types of measures reported, proportion of studies reporting ≥2 measures and mean (±SD) number of measures per study were determined for all studies and compared between subgroups.. Through the use of a standardised data extraction tool, we independently extracted all data, with disagreements resolved by a separate investigator.. 148 studies were included, 57% of which reported ≥2 control measures (mean/study=2.13±1.36). The proportion of time spent in the target international normalised ratio range (TTR) was most commonly reported (79%), and was frequently accompanied by time above/below range (52%). AF studies more frequently reported ≥2 control measures compared with VTE studies (63% vs 37%; p=0.004), and reported a greater number of measures per study (mean=2.36 vs 1.53; p<0.001). Observational studies were more likely to provide ≥2 measures compared with randomised trials (76% vs 33%; p<0.001) and report a greater number of measures (mean=2.58 vs 1.63; p<0.001). More recent studies (2004-2013) reported ≥2 measures more often than older (2000-2003) studies (59% vs 35%; p=0.05) and reported more measures per study (mean=2.23 vs 1.48; p=0.02).. While TTR was often utilised, studies reported ≥2 measures of VKA control only about half of the time and lacked consistency in the types of measures reported. A trend towards studies reporting greater numbers of VKA control measures over time was observed over our review time horizon, particularly, with AF and observational studies.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Studies as Topic; Drug Monitoring; Humans; International Normalized Ratio; Venous Thromboembolism; Vitamin K

Cardiovascular disease remains a major cause of morbidity and mortality in developed countries. New treatments, in the form of novel oral anticoagulants (NOAC) that reduce thrombotic risk are now available for patients with atrial fibrillation (AF) or acute coronary syndrome (ACS). Warfarin has been the cornerstone of thromboprophylaxis in patients with AF, but treatment is cumbersome, inconvenient and often unreliable, with fluctuating time in therapeutic range. Thrombotic events also continue to occur in a significant number of ACS patients despite antiplatelet therapy. Thus there is an unfilled need to reduce thrombotic events in ACS and AF patients. NOAC comprise direct factor Xa inhibitors (apixaban, rivaroxaban, darexaban, edoxaban), direct thrombin inhibitors (dabigatran) and PAR-1 antagonists (vorapaxar, atopaxar). In this review, we compare and contrast NOACs and review their individual and specific clinical trial database in ACS and AF. In the setting of ACS, the role of NOAC is unclear, as any reduction in ischemic events appears to be offset by hemorrhagic risk. However, NOAC have a definite place in the treatment of patients with non-valvular AF, where they are at least as effective, if not superior to warfarin.

Topics: Acute Coronary Syndrome; Administration, Oral; Animals; Anticoagulants; Antithrombins; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Thrombosis; Vitamin K

Warfarin, a vitamin K antagonist, is the most widely used oral anticoagulant in the world. It is cheap and effective, but its use is limited in many patients by unpredictable levels of anticoagulation, which increases the risk of thromboembolic or haemorrhagic complications. It also requires regular blood monitoring and dose adjustment. New classes of drugs, non-vitamin K antagonist oral anticoagulants (NOACs), are now supported as alternatives to warfarin. Three NOACs are licensed: dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, antagonists of factor Xa. NOACs do not require routine blood monitoring or dose adjustment. They have a rapid onset and offset of action and fewer food and drug interactions. Current indications include treatment and prophylaxis of venous thromboembolism and prevention of cardioembolic disease in non-valvular atrial fibrillation. Effective antidotes are lacking and some caution must be used in severe renal impairment, but favourable trial evidence has led to their widespread adoption. Research is ongoing, and an increase in their use and indications is expected in the coming years.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Drug Administration Schedule; Evidence-Based Medicine; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Venous Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) is the most common arrhythmia and brings about significant mortality and morbidity as a result of heart failure and ischemic stroke. Besides vitamin K antagonists (VKA), several new pharmacological agents (nonvitamin K antagonist oral anticoagulants [NOACs]) and procedures have since been developed to improve stroke prevention efforts in AF.. This paper will discuss the antiplatelet agents, VKA and NOACs, and their efficacy and safety for stroke prevention in AF. Focus will be placed on the NOACs, their limitations and special considerations. A short assessment of other nonpharmacological antithrombotic procedures will also be made. An extensive PubMed search was used to identify suitable papers.. Despite the advent of NOACs, the VKAs will remain as an important oral anticoagulant due to its versatility. However, convenience and limited food or drug interactions will make NOACs attractive options. The choice between various NOACs will depend on several important factors as illustrated below. Over time, the role for antiplatelet agents will gradually diminish. Left atrial appendage occlusion devices have shown promising results and may have the potential to change the way clinicians manage thromboembolism risks related to AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Platelet Aggregation Inhibitors; Stroke; Thromboembolism; Vitamin K

Anticoagulants are effective at preventing and treating thrombosis, but can cause bleeding. For decades, vitamin K antagonists (VKAs) have been the only available oral anticoagulants. The development of non-VKA oral anticoagulants (NOACs), which inhibit either factor Xa or thrombin stoichiometrically, has provided alternatives to VKAs for several indications. The results of recent large-scale randomised controlled trials comparing NOACs with VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) have produced some unexpected results. As a group, NOACs showed similar efficacy as warfarin, but a reduced risk of major bleeding. The reduction in bleeding with NOACs was greatest with intracranial hemorrhage. In contrast, the relative risk of gastro-intestinal bleeding was increased with some NOACs. In this review, we explore the potential mechanisms as well as the implications of these organ-specific bleeding patterns.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Endothelium, Vascular; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intestinal Absorption; Intracranial Hemorrhages; Organ Specificity; Randomized Controlled Trials as Topic; Stroke; Thrombophilia; Thromboplastin; Vitamin K; Warfarin

The incidence of intracranial bleeding is known to be markedly higher in Japan and other East Asian countries than in countries outside of East Asia. Non-vitamin K antagonist oral anticoagulants (NOACs) have much lower risk of intracranial bleeding than warfarin, so we reviewed the effect of this class of drugs on intracranial bleeding in Asian patients with non-valvular atrial fibrillation (NVAF). Warfarin therapy in Asian or East Asian populations appears to be associated with lower efficacy, poorer safety and a much greater risk of intracranial bleeding when compared with non-Asian or non-East Asian groups. Reflecting the higher incidence of intracranial bleeding in Asia and East Asia, Asian physicians in charge usually keep the prothrombin time-international normalized ratio (PT-INR) lower than is the case in Western countries. Irrespective of the lower PT-INR of warfarin, the incidence of intracranial bleeding is still high in Asia and East Asia. Because each NOAC strongly reduces the incidence of intracranial bleeding when compared with warfarin, use of dabigatran, rivaroxaban, apixaban or edoxaban would seem the best option for stroke prevention when treating Asian patients, including Japanese with NVAF.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Japan; Stroke; Vitamin K

Atrial fibrillation (AF) and coronary heart disease (CHD) commonly occur together. Previous consensus guidelines were published before the wide availability of novel oral anticoagulants (NOACs) and newer P2Y12 antiplatelet agents. We examine recent evidence to guide management in 3 categories of patients with AF and CHD: patients with stable CHD, nonstented patients with recent acute coronary syndrome, and patients with a coronary stent requiring dual-antiplatelet therapy.. We conducted a literature search by evaluation of PubMed and other data sources including international meeting reports. We critically reviewed recent clinical trial and relevant registry evidence to update European and US consensus documents.. Oral anticoagulation with warfarin or NOACs is required to prevent embolic stroke in AF, and antiplatelet therapy is insufficient for this purpose. Antiplatelet therapy using monotherapy with aspirin is the standard of care in stable CHD. Dual-antiplatelet therapy with aspirin and clopidogrel or a new P2Y12 inhibitor (dual-antiplatelet therapy) is needed to reduce coronary events after an acute coronary syndrome or after percutaneous coronary intervention. Combinations of these agents increase the risk of bleeding, and limited clinical trial evidence suggests that withdrawal of aspirin may reduce bleeding without increasing coronary events.. Available clinical trials and registries provide remarkably little evidence to guide difficult clinical decision making in patients with combined AF and CHD. In patients on triple antithrombotic therapy with vitamin K antagonists, aspirin, and clopidogrel, a single clinical trial indicates that withdrawal of aspirin may reduce bleeding risk without increasing the risk of coronary thrombosis. It is unclear whether this evidence applies to combinations of NOACs and newer P2Y12 inhibitors. Clinical trials of combinations of the newer antithrombotic agents are urgently needed to guide clinical care.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticlopidine; Vitamin K; Warfarin

Chronic oral anticoagulant therapy is recommended (class I) in patients with mechanical heart valves and in patients with atrial fibrillation with a CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65 to 74 years, Sex category) score ≥1. When these patients undergo percutaneous coronary intervention with stenting, treatment with aspirin and a P2Y12 receptor inhibitor also becomes indicated. Before 2014, guidelines recommended the use of triple therapy (vitamin K antagonists, aspirin, and clopidogrel) for these patients. However, major bleeding is increasingly recognized as the Achilles' heel of the triple therapy regimen. Lately, various studies have investigated this topic, including a prospective randomized trial, and the evidence for adding aspirin to the regimen of vitamin K antagonists and clopidogrel seems to be weakened. In this group of patients, the challenge is finding the optimal equilibrium to prevent thromboembolic events, such as stent thrombosis and thromboembolic stroke, without increasing bleeding risk.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Ticlopidine; Vitamin K

The main purpose of anticoagulants is to diminish fibrin formation, thereby decreasing the risk of venous or arterial thrombosis. Vitamin K antagonist have been used for many decades in order to achieve reduced thrombotic risk, despite major drawbacks of this class of drugs such as cumbersome dossing and monitoring of anticoagulant status. To overcome these drawbacks of VKA, new classes of anticoagulants have been developed including oral anticoagulants for direct inhibition of either thrombin or factor Xa, which can be administrated in a fixed dose without monitoring. Coagulation factors can activate cellular protease-activated receptors, thereby inducing cellular processes as inflammation, apoptosis, migration, and fibrosis. Therefore, inhibition of coagulation proteases not only attenuates fibrin formation, but may also influence pathophysiological processes like vascular calcification and atherosclerosis. Animal models revealed that VKA therapy induced both intima and media calcification and accelerated plaque vulnerability, whereas specific and direct inhibition of thrombin or factor Xa attenuated atherosclerosis. In this review we provide an overview of old and new oral anticoagulants, as well discuss potential pleiotropic effects with regard to calcification and atherosclerosis. Although translation from animal model to clinical patients seems difficult at first sight, effort should be made to fully understand the clinical implications of long-term oral anticoagulant therapy on vascular side effects.

Topics: Animals; Anticoagulants; Antithrombins; Atherosclerosis; Atrial Fibrillation; Blood Coagulation Factors; Calcinosis; Coumarins; Disease Models, Animal; Disease Progression; Drug Monitoring; Enzyme Activation; Factor Xa Inhibitors; Hemorrhage; Humans; Practice Guidelines as Topic; Protease Inhibitors; Randomized Controlled Trials as Topic; Receptors, Proteinase-Activated; Stroke; Thrombosis; Vitamin K

Non-valvular atrial fibrillation is one of the most important risk factor for embolic cerebral infarcts. Besides vitamin K antagonists, recently developed novel oral anticoagulants are gaining an increasing role in its treatment. Dabigatran, rivaroxaban and apixaban are novel oral anticoagulants available in the routine clinical practice. This review summarizes their use and the corresponding guidelines in the secondary prevention of ischemic stroke, by answering questions raised in relation of a hypothetical case report.. A nem valvularis eredetű pitvarfibrilláció az embóliás agyi infarktusok egyik legfontosabb kockázati tényezője. Kezelésében a K-vitamin-antagonisták mellett az elmúlt években megjelenő új típusú orális antikoagulánsok egyre nagyobb teret kapnak. A dabigatran, a rivaroxaban és az apixaban a klinikai gyakorlatban elérhető új típusú orális antikoagulánsok. Az összefoglaló ezek alkalmazásának irányelveit, tulajdonságaikat tekinti át ischaemiás stroke szekunder prevenciójában, hipotetikus esetismertetés kapcsán felmerülő kérdéseket tárgyalva. Orv. Hetil., 2014, 155(42), 1655–1660.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Vitamin K; Warfarin

The majority of patients with nonvalvular atrial fibrillation (AF) will require anticoagulation therapy for reducing the risk of stroke, the most devastating complication of AF. Although traditionally vitamin K antagonists have been used for this purpose, they have important limitations that interfere with their use in clinical practice. Different clinical trials have shown the benefits of new oral anticoagulants over warfarin, but patients included in the ROCKET-AF trial were found to be at a higher risk of AF-related complications. Moreover, rivaroxaban has been proven to be effective and safe in patients with AF and moderate renal dysfunction as well as in those with ischemic heart disease. Rivaroxaban is taken only once daily; this may improve medication adherence and, secondarily, it provides a higher protection and reduction in the risk of stroke. This article provides an extensive review of the available evidence about rivaroxaban, with a special focus on nonvalvular AF.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Humans; Ischemic Attack, Transient; Medication Adherence; Morpholines; Renal Insufficiency; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Thromboembolism; Vitamin K; Warfarin

Clinical trials have shown that anticoagulation with vitamin K antagonists (VKAs), e.g. warfarin, decreases the risk of stroke in patients with atrial fibrillation (AF); however, increased bleeding risk is one of the safety concerns. The primary objective was to conduct a systematic review of the published literature, assessing the risk of major bleeding and mortality in patients with AF treated with VKAs.. Online searches of MEDLINE, EMBASE, BIOSIS, and the Cochrane Library were performed to a pre-specified protocol from 1960 to March 2012 for randomized controlled trials (RCTs) and from January 1990 to March 2012 for observational studies. A total of 47 studies (16 RCTs and 31 observational studies) were included. Cumulative follow-up was 61,563 patient-years for RCTs and 484 241 patient-years for observational studies. The overall median incidence of major bleeding was 2.1 per 100 patient-years (range, 0.9-3.4 per 100 patient-years) for RCTs and 2.0 per 100 patient-years (range, 0.2-7.6 per 100 patient-years) for observational studies. With study year as a proxy for changing management patterns, some evidence of bleeding rates and/or their reporting increasing over time was noted. Mortality rates from observational studies were inadequately reported to allow comparison with those from RCT data.. The median rate of major bleeding in observational studies and RCTs is similar. The larger heterogeneity in bleeding rates observed in a real-life setting could reflect a high variability in standard of care of patients on VKAs and/or methodological differences between observational studies and/or variability in data sources.

Topics: Anticoagulants; Atrial Fibrillation; Comorbidity; Evidence-Based Medicine; Hemorrhage; Humans; Incidence; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Thromboembolism; Vitamin K

The usefulness of anticoagulation in patients with atrial fibrillation (AF) is well known. However, the inherent limitations of vitamin K antagonists (VKAs) have made the development of new oral anticoagulants necessary. Drugs directed against thrombin or the factor Xa are currently available.. These molecules, being administered at fixed doses and not requiring laboratory monitoring, overcome one crucial problem associated with the use of VKAs. However, data about the bleeding risk related to the use of these molecules should be further analyzed.. The efficacy of direct anticoagulants (DACs) in AF-related stroke prevention has been considered the primary outcome in all Phase III published trials. On the other hand, the reduction of the bleeding risk is an important goal achieved by the DACs as compared with VKAs. Besides data deriving from randomized trials, when talking about new drugs, the need of evidences from the 'everyday clinical practice' are often requested. The aim of this literature revision is to report and analyze data from specific subgroups about which little is known. In particular, information about the use of DACs in oncologic patients, in patients receiving concomitant antiplatelet drugs and in the perioperative period is currently lacking. The parallel evaluation of all these data may lead to the identification of clinical and demographical criteria to choose when to switch to DACs.

Topics: Animals; Anticoagulants; Antimetabolites; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Drugs, Investigational; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

Within a few decades half of the patients with non-valvular atrial fibrillation (AF) will be older than 80 years. These patients are at particularly high risk of thromboembolism (Scylla) but also of the hemorrhagic complications of thromboprophylaxis (Charybdis). A frequent compromise is to use as antithrombotic agents instead of vitamin-K antagonists aspirin or other antiplatelet drugs, which are ineffective for thromboprophylaxis in the oldest old and definitely not free from a high risk of severe bleeding. All the new direct anticoagulants currently licensed (dabigatran, rivaroxaban, apixaban) are at least as effective as warfarin for thromboprophylaxis in AF, but the risk of the intracranial bleeding, the most feared complication of anticoagulant therapy, is at least halved. In the oldest patients of 80 years of age or more preliminary data, available so far only for dabigatran, indicate that the favorable outcomes of direct anticoagulants are also present in this subgroup, often left untreated for fear of intracranial bleeding. The choice between the different direct anticoagulants is driven by the presence or not of renal insufficiency, the presence and degree of multimorbidity and polypharmacy and by the likelihood or not of poor treatment adherence in patients who are often frail and with some degree of cognitive impairment.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Medication Adherence; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Vitamin K

Atrial fibrillation is the most common clinically relevant heart rhythm disorder and is associated with increased morbidity and mortality. Most important risk factors for atrial fibrillation are high age, arterial hypertension, diabetes mellitus, heart failure and rheumatic heart disease. Chronic atrial fibrillation is classified as paroxysmal, persistent, long-standing persistent and permanent atrial fibrillation. Spontaneous conversion to sinus rhythm is observed in paroxysmal atrial fibrillation, whereas in persistent atrial fibrillation, pharmacological or electrical cardioversion is required in order to restore sinus rhythm. In permanent atrial fibrillation, the arrythmia is accepted by patient and physician and cardioversion is not attempted. Rate control only is thus applied in permanent atrial fibrillation, whereas in paroxysmal and persistent atrial fibrillation, addition rhythm control with anti-arrhythmic drugs and/or ablation is attempted if symptoms persist and age and co-morbidities do not pose contra-indications. Besides rhythm management, oral anticoagulation is the mainstay of therapy for most patients with atrial fibrillation. Risk scores such as the CHA2DS2-VASc score help to identify patients with a high risk of stroke and need for oral anticoagulation. The underuse of vitamin K antagonists in clinical practise is partly due to considerable disadvantages: an increased bleeding risk, a narrow therapeutic window and multiple drug interactions prompting frequent laboratory controls to assess an individual dosage. New oral anticoagulants targeting thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban and edoxaban) may replace warfarin in many patients with atrial fibrillation due to convincing data both on efficacy and safety as well as convenience. However, challenges remain with respect to lack of specific antidotes and high costs.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Electric Countershock; Heart Rate; Humans; Platelet Aggregation Inhibitors; Risk Factors; Stents; Stroke; Vitamin K

The recent introduction of new oral anticoagulants or novel target specific oral anticoagulants (TSOA's) is likely to have a major impact in the years ahead. Many large clinical trials have been published in the past few years showing these agents are generally safe and effective in several clinical settings including acute venous thromboembolic disease, prophylaxis in the postoperative setting, prevention of thromboembolism in patients with atrial fibrillation, and in the management of acute coronary syndromes. Reported rates of overall and intracranial bleeding are lower compared to oral vitamin K antagonists. Other major advantages of oral direct thrombin inhibitors (dabigatran) and Xa inhibitors (rivaroxaban and apixaban) include rapid onset and offset of action and predictable pharmacodynamics with relatively wide therapeutic window allowing for unmonitored drug use. The relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use of these agents. In this review we focus on some practical issues related to TSOA's including some limitations, potential complications, considerations to be made for certain patient populations, periprocedural management and issues pertaining to transition to and from these novel agents.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Delivery Systems; Factor Xa Inhibitors; Female; Half-Life; Humans; Male; Postoperative Care; Thromboembolism; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Pulmonary Embolism; Stroke; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Vitamin K antagonists (VKAs) prevent stroke in atrial fibrillation (AF) at the cost of bleeding risk. To determine major bleeding rates in AF patients, we conducted a systematic review that identified 51 eligible studies including more than 342,699 patients. The pooled estimate of the rate of major bleeding was 2.51 (99% confidence interval: 2.03-3.11) bleeds per 100 patient-years. The results represent the best estimates of bleeding risk that most patients contemplating VKA use may expect.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Vitamin K

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Cerebral Hemorrhage; Dabigatran; Factor Xa Inhibitors; Humans; Monitoring, Physiologic; Morpholines; Prodrugs; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Thrombin; Thromboembolism; Vitamin K; Warfarin

Strategies to prevent stroke recurrences and stroke-related morbidity and mortality are a major concern for healthcare systems worldwide. Antithrombotic therapy is the cornerstone for the secondary prevention of ischemic stroke.. This article is an overview of currently used antithrombotic therapies in the management of ischaemic stroke with special focus on their pharmacokinetic properties and how these properties may influence their clinical utility. This review covers both antiplatelet drugs and antitcoagulants used in the primary and secondary prevention of ischaemic stroke.. The role of aspirin in the early management of stroke is well established. Furthermore, antiplatelet drugs (aspirin, aspirin/dypiridamol and clopidogrel) are the cornerstone of secondary prevention of ischaemic stroke, while their role in the primary prevention is less well established. There are limited data on the use of novel antiplatelet agents for the management of stroke patients. Anticoagulation has not been associated with clinical benefits when used early in the management of acute ischaemic stroke. Long-term therapy with vitamin K antagonists provides prognostic benefit in patients with atrial fibrillation and additional stroke risk factors. New oral anticoagulants have demonstrated at least similar efficacy with vitamin K anatagonists in preventing stroke in patients with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Cilostazol; Clopidogrel; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Stroke; Tetrazoles; Thiophenes; Thrombin; Ticlopidine; Vitamin K

Non-valvular AF is the most common cardiac arrhytmia. Its incidence increases with age. AF is an independent risk factor for ischaemic stroke, representing a five times higher risk for it, associated with a high mortality rate. Beside AF, there are several other risk factors which influence the risk of stroke. Stroke risk calculator can be used to assess the risk of patient having a stroke. The most endangered group of patients with AF are those who have already suffered from cerebrovascular event. The only effective medication for prevention of stroke due to AF had been the application of vitamin K antagonists (VKA) which considerably decrease the rate of ischaemic event in a patient with AF providing that the INR is in the therapeutic range. VKA have several limitations of use in clinical practice and the fear of bleeding complications results an underusing of these drugs. Only 50% of all patients treated with VKA reaches the therapeutic range of INR. The breakthrough of prevention of stroke in recent years is undisputedly the coming out of novel oral anticoagulants (NOACs, thrombin and Xa-factor inhibitors). Recent studies suggest that these novel drugs prove the same efficacy as VKA drugs, furthermore dabigatran in a dose of 2 x 150 mg or apixaban in 2 x 5 mg was statistically superior to warfarin in the prevention of stroke. NOACs have shown a large reduction in intracranial hemorrhage compared with warfarin. They are given as a fixed dose and do not require persistent monitoring making them much more convenient. NOACs at guidelines of European Society of Cardiology act as a preferable drugs in case of ischaemic stroke with AF Probably the extended use of NOACs in clinical practice will be the mainstream of stroke prevention in the future.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Brain Ischemia; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; International Normalized Ratio; Intracranial Hemorrhages; Pyridines; Risk Assessment; Risk Factors; Stroke; Vitamin K

Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs.. To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF.. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE (1950 to April 2013) and EMBASE (1980 to April 2013). In an effort to identify further published, unpublished and ongoing trials we searched trials registers and Google Scholar (July 2012). We also screened reference lists and contacted pharmaceutical companies, authors and sponsors of relevant published trials.. Randomised controlled trials that directly compared the effects of long-term treatment (more than four weeks) with factor Xa inhibitors and VKAs for the prevention of cerebral and systemic embolism in patients with AF. We included patients with and without a previous stroke or TIA.. The primary efficacy outcome was the composite endpoint of all strokes and other systemic embolic events. Two authors independently assessed trial quality and the risk of bias, and extracted data. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. However, in the case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects and performed a pre-specified sensitivity analysis excluding any fully open-label studies.. We included data from 42,084 participants randomised into 10 trials. All participants had a confirmed diagnosis of AF (or atrial flutter) and were deemed by the randomising physician to be eligible for long-term anticoagulant treatment with a VKA (warfarin) with a target International Normalised Ratio (INR) of 2.0 to 3.0 in most patients. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux or rivaroxaban. Four trials were double-masked, five partially-masked (that is different doses of factor Xa inhibitor administered double-masked and warfarin administered open-label) and one was open-label. Median duration of follow-up ranged from 12 weeks to 1.9 years.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in nine of the included studies (40,777 participants). Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin (OR 0.81, 95% CI 0.72 to 0.91). We also analysed both components of this composite endpoint separately: treatment with a factor Xa inhibitor significantly decreased both the number of ischaemic and haemorrhagic strokes (OR 0.78, 95% CI 0.69 to 0.89) and the number of systemic embolic events (OR 0.53, 95% CI 0.32 to 0.87).All of the included studies (42,078 participants) reported the number of major bleedings. Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.89, 95% CI 0.81 to 0.98). There was, however, statistically significant and high heterogeneity (I² = 81%) and an analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings (OR 0.92, 95% CI 0.63 to 1.34). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.84, 95% CI 0.76 to 0.92) but moderate heterogeneity was still observed (I² = 65%). A similar sensitivity analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings in patients treated with factor Xa inhibitors (OR 0.78, 95% CI 0.57 to 1.05). Part of the observed heterogeneity can thus be explained by the increased risk of major bleedings in the fac. Factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in patients with AF. Factor Xa inhibitors also seem to reduce the number of major bleedings and ICHs compared with warfarin, though the evidence for a reduction of major bleedings is somewhat less robust. There is currently no conclusive evidence to determine which factor Xa inhibitor is more effective and safer for long-term anticoagulant treatment of patients with AF as head-to-head studies of the different factor Xa inhibitors have not yet been performed.

Topics: Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Humans; Intracranial Embolism; Randomized Controlled Trials as Topic; Vitamin K

The new oral anticoagulants (NOACs) dabigatran etexilate, rivaroxaban, and apixaban have been extensively studied for prevention and treatment of venous thromboembolic disease and for stroke prevention in atrial fibrillation. Elderly patients have the highest incidence of thrombotic complications but also have the highest risk of anticoagulant associated bleeding. In this review we critically examine the balance between risks and benefits of NOACs compared with vitamin K antagonists in elderly patients enrolled in phase 3 randomized controlled trials for the management of venous thrombosis and stroke prevention in atrial fibrillation. Results show that the favourable balance between risks and benefits of NOACs is preserved in the elderly population.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Drug Administration Schedule; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

For more than 5 decades, the only available treatment for the prevention of atrial fibrillation (AF)-related stroke were the vitamin K antagonists. Recently, novel oral anticoagulants (NOAC) have been approved for the prevention of AF-related stroke. In the present article, the cost effectiveness of AF-related stroke-prevention strategies is reviewed. The emphasis on NOACs aims to provide an overview of their impact on health economics based on the published cost-effectiveness analyses. The available evidence suggests that the balance from the efficacy and safety point of view makes the treatment with the NOACs a cost-effective alternative to warfarin. Thus, the NOACs offer efficacy, safety and convenience, as well as cost effectiveness, for stroke prevention in AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Drug Approval; Humans; Stroke; Vitamin K; Warfarin

Vitamin K antagonists (VKAs) are the most widely used anticoagulants for stroke prevention in patients with atrial fibrillation (AF). Recently, the US FDA approved three novel anticoagulants that work through inhibition of coagulation cascade independent of Vitamin K-dependent enzymatic reactions and, therefore, should have less food-drug interactions. Since AF is a disease of the aging heart, it is important to assess safety and efficacy of these new anticoagulants in elderly patients. We reviewed age-related changes in pharmacokinetics and pharmacodynamics observed with senescence and the effects of these changes on novel anticoagulants, known and anticipated drug and food interactions, and challenges related to bleeding complications and temporary discontinuation prior to surgery or interventional procedure. Although advantageous to VKA in age groups represented in trials, there are lack of data on VKA usage in older-elderly patients; additional research and post-marketing analysis in older-elderly patients are needed.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Factor Xa Inhibitors; Humans; Monitoring, Physiologic; Stroke; Thrombin; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Brain Infarction; Dabigatran; Humans; Intracranial Embolism; Ischemic Attack, Transient; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Vitamin K

With the recent marketing of the new oral anticoagulants (NOAC), the future of vitamin k antagonist (VKA) needs to be redefined. VKAs are drugs with a narrow therapeutic margin and a high iatrogenic risk that requires a close biological monitoring. Their efficacy has been proven for atrial fibrillation in numerous populations, especially in the elderly. Their side effects and interactions are well known. The measurement of the level of anticoagulation is possible and reliable using the INR (international normalized ratio) and an antidote is usable in case of emergency. The NOAC are at least as effective as VKA with slightly less side-effects especially cerebral hemorrhage, and they do not require biological monitoring. However, data on efficacy and side-effects of NOAC rely mainly on phase III clinical trials that did not particularly target polypathologic and frail populations. In these populations, we therefore have more "real life" information on VKA than NOAC. But studies on NOAC are currently conducted among these populations. A conservative approach would be to maintain VKA to older patients with stable INR. Lastly VKA are the only anticoagulant usable in case of severe renal failure and valvular fibrillation.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Comorbidity; Dose-Response Relationship, Drug; Frail Elderly; Humans; International Normalized Ratio; Intracranial Embolism; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Atrial fibrillation treatment relies on anticoagulation therapy that reduces the risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant drugs for more than 50 years, but they are difficult to manage especially in the elderly. In France, VKA are the main cause of iatrogenic hospitalizations with about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year. Pharmacologic properties of VKA, especially the narrow therapeutic margin explain the complexity of their management. Several studies have shown that patients treated with VKA were on average only 50% of the time with an INR in the therapeutic range. In other words, patients are, half of the time, either-under treated or over-treated. Within this framework, development of new oral anticoagulant drugs appeared necessary, in order to obtain drugs with larger therapeutic margin and a better risk/benefit profile than VKA. Three large randomized clinical trials including almost 50,000 patients with 20,000 subjects over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total mortality. Meanwhile, their renal elimination and the lack of control of the biological efficacy need to be taken into account for their prescription. Renal failure (estimated glomerular filtration rate according to Cockcroft formula < 30 mL/min) contraindicates their use. Their half-life is shorter than that of VKA and the biological monitoring is not available, thus a good adherence to the treatment is important. Studies specifically conducted among geriatric older population with poly-pathologies and frail are therefore needed to evaluate tolerance of NOAC in real life conditions.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Drugs, Investigational; Half-Life; Humans; Intracranial Embolism; Metabolic Clearance Rate; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Stroke; Thiophenes; Vitamin K

Oral anticoagulation is a widely used treatment and atrial fibrillation (AF) is the most frequent indication. We review the therapeutic options on an important clinical challenge: rapid reversal anticoagulation in the setting of an urgent invasive procedure. We report a case of a 71-year-old man treated with warfarin who was over-anticoagulated when presented to the emergency department for syncope due to severe bradiarrhythmia and needed temporary pacing. Intravenous infusion of vitamin-k was not adequate for rapid reversal over anticoagulation whereas the administration of a Prothrombin Complex Concentrate (PCC) was able to quickly reverse anticoagulant activity and allowed the performance of an urgent invasive procedure without hemorrhagic complication. The aim of this paper is to draw attention to possible therapeutic strategies to reduce the risk of bleeding related to over-anticoagulation with vitamin-K antagonists (VKAs) in case of urgent invasive procedure, emphasizing the role of PCC in keeping with national and international guidelines.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Blood Loss, Surgical; Humans; Male; Pacemaker, Artificial; Vitamin K; Warfarin

New orally administered anticoagulants will simplify stroke-prevention strategies in patients with atrial fibrillation (AF). Novel anticoagulants, such as dabigatran etexilate, a direct thrombin inhibitor, and rivaroxaban, a direct factor Xa inhibitor, have been approved by the US Food and Drug Administration for the prevention of stroke and systemic embolism in patients with nonvalvular AF. In addition, the factor Xa inhibitor apixaban has been reported to be as effective as warfarin in a large, randomized clinical trial, and the efficacy of edoxaban is being assessed in a phase III warfarin comparison trial. This review discusses the limitations of vitamin K antagonist therapy for patients with AF and establishes the need for alternative, effective anticoagulation with an improved benefit-risk ratio for the prevention of stroke. Novel anticoagulants have the potential to provide convenient, effective stroke prophylaxis without many of the issues inherent in the use of traditional agents.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Stroke; Vitamin K

Decision making with regard to thromboprophylaxis should be based upon the absolute risks of stroke/thromboembolism and bleeding and the net clinical benefit for a given patient. As a consequence, a crucial part of atrial fibrillation (AF) management requires the appropriate use of thromboprophylaxis, and the assessment of stroke as well as bleeding risk can help inform management decisions by clinicians. The objective of this review article is to provide an overview of stroke and bleeding risk assessment in AF. There would be particular emphasis on when, how, and why to use these risk stratification schemes, with a specific focus on the CHADS2 [congestive heart failure, hypertension, age, diabetes, stroke (doubled)], CHA2DS2-VASc [congestive heart failure or left ventricular dysfunction, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)], and HAS-BLED [hypertension (i.e. uncontrolled blood pressure), abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR (if on warfarin), elderly (e.g. age >65, frail condition), drugs (e.g. aspirin, NSAIDs)/alcohol concomitantly] risk scores.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Biomarkers; Echocardiography; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Practice Guidelines as Topic; Renal Insufficiency; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Vitamin K

Prevention of atrial fibrillation (AF)-related stroke and thromboembolism is an important part of AF management. However, stroke risk varies considerably with associated morbidities and risk factors. Several stroke risk stratification schemes have been developed, and categorize patients' stroke risk into categories based on the presence and combination of risk factors. Based on the perceived level of risk, current guidelines recommend that patients with AF receive some form of antithrombotic therapy. Despite guideline recommendations, however, many patients with AF do not receive adequate thromboprophylaxis. This review will discuss some of the reasons why guidelines are not adhered to in clinical practice and current gaps in knowledge. Low adherence to guidelines is in part related to the drawbacks associated with vitamin K antagonist therapy and to the imperfection of current schemes for stratification of both thromboembolic and bleeding risks. Such drawbacks have highlighted the need for new anticoagulants for the prevention of stroke in patients with AF. The novel oral anticoagulants in development, four of which - dabigatran, rivaroxaban, apixaban and edoxaban - have completed or are completing phase III testing, may overcome some of the limitations of vitamin K antagonist therapy and address the underuse and safety concerns associated with current antithrombotic therapies in patients with AF.

Topics: Atrial Fibrillation; Fibrinolytic Agents; Humans; Pyrazoles; Pyridones; Vitamin K

Patients with nonvalvular atrial fibrillation (AF) and risk factors for stroke need anticoagulation to avoid thromboembolic complications. Vitamin K antagonists (VKAs) are an established pharmacological group the use of which is recommended by guidelines. However, VKAs (like warfarin) have major disadvantages, such as a variable dose-effect relationship, drug and food interactions, the need for regular blood testing and dose titration, and, finally, a substantial risk of bleeding. New oral anticoagulants are intended to replace warfarin, being at least as safe and effective, and lacking some of the disadvantages of VKAs. Clinical data for dabigatran, rivaroxaban, apixaban and edoxaban, and other new drugs, are discussed in this article with special focus on their use in nonvalvular AF.

Topics: Anticoagulants; Atrial Fibrillation; Drug Design; Drug Monitoring; Hemorrhage; Humans; Risk Factors; Stroke; Thromboembolism; Vitamin K; Warfarin

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Topics: Anticoagulants; Atrial Fibrillation; Cardiology; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Myocardial Infarction; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Research Design; Stroke; Treatment Outcome; Vitamin K; Warfarin

Stroke is a common disease, which is associated with high morbidity and high mortality. Up to 25% of cerebral ischaemic infarcts are caused by cardio-embolic events, most commonly associated with atrial fibrillation. It has previously been shown that antithrombotic therapy is insufficiently used in patients at increased risk of stroke. This article reviews evidence and practical management of anticoagulant therapy in stroke patients and provides an update on risk stratification for thromboembolism and bleeding complications in patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Brain Ischemia; Cerebral Hemorrhage; Dabigatran; Female; Humans; Male; Morpholines; Pyrazoles; Pyridones; Radiography; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Thiophenes; Thromboembolism; Vitamin K

Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter-individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban have recently been investigated to prove whether they fulfill the high expectancy of an ideal anticoagulant with respect to a more favorable efficacy/safety profile and without the need for coagulation controls, thereby improving quality of life. Dabigatran (RE-LY) achieved an impressive reduction in stroke and non-central nervous system (non-CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year) in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable action on bleeding hazards. The results of rivaroxaban which were obtained in the ROCKET AF study (on treatment analysis: stroke and non-CNS embolism: 1.7%/year vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally, compared to aspirin, apixaban reduced the combined primary efficacy endpoint by 52% with comparable rates of bleeding (AVERROES). This review gives a summary of the current knowledge about these agents and their potential future importance.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Quality of Life; Stroke; Thrombin; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of thromboembolic complications and stroke. Therefore, the implementation of thromboembolic preventive treatment is the cornerstone of quality management in AF patients. During the last 60 years, vitamin K antagonists remain at the forefront of antithrombotic management of AF patients. Randomized trials have demonstrated their superiority over aspirin as well as over the combination of aspirin and clopidogrel with similar safety profile. However, the disseminated use of vitamin K antagonists among suitable candidates is hampered by their inherent limitations. As a result, a considerable proportion of AF patients do not receive this life-saving therapy. In the last few years, novel anticoagulants targeting factors IIa (dabigatran) and Xa (rivaroxaban, apixaban, edoxaban) in the coagulation cascade have been developed. Recently completed phase III mega-trials of dabigatran, rivaroxaban and apixaban have provided cumulative evidence in favor of these novel anticoagulants. Their main advantages, apart from their treatment efficacy, include the reduced rate of intracranial hemorrhage, the lack of need for routine coagulation monitoring, the predictable anticoagulation response and the limited interaction with food and drugs. In the present manuscript we present a critical appraisal of the recent trials focusing on issues that are expected to influence decision making on selection of novel anticoagulants.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Platelet Aggregation Inhibitors; Stroke; Vitamin K

Oral anticoagulation with vitamin K antagonists (warfarin, phenprocoumon) is successful in both primary and secondary stroke prevention in patients with atrial fibrillation, yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26%. However, these agents have a number of well documented shortcomings. Acetylsalicylic acid (ASA) reduces the relative risk of stroke by a nonsignificant 19% compared with placebo, and increased bleeding risk offsets any therapeutic gain from the combination of ASA with clopidogrel. This review describes the current landscape and developments in stroke prevention in patients with atrial fibrillation, with special reference to secondary prevention.. A number of new drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists are under investigation. These include direct factor Xa inhibitors and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES, ARISTOTLE) provide promising results for new agents, including higher efficacy and significantly lower incidences of intracranial bleeds compared with warfarin. The new substances show similar results in secondary as in primary stroke prevention in patients with atrial fibrillation.. New anticoagulants add to the therapeutic options for patients with atrial fibrillation, and offer a number of advantages over warfarin, for both the clinician and patient, including a favourable bleeding profile and convenience of use. Consideration of these new anticoagulants will improve clinical decision making.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Decision Making; Factor Xa Inhibitors; Humans; Risk Factors; Stroke; Thrombin; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiotonic Agents; Humans; Risk Factors; Thromboembolism; Vitamin K

For more than 60 years, vitamin K antagonists have been the only available oral anticoagulants for the prevention of stroke and systemic embolism in atrial fibrillation (AF). Several new molecules, with a favorable pharmacokinetic profile and avoiding routine monitoring, have been recently developed, opening a new era in anticoagulation. The oral direct thrombin inhibitor, dabigatran, and the oral activated factor X inhibitors, rivaroxaban and apixaban, are the novel oral anticoagulants with data from large randomized clinical trials showing that these drugs are noninferior to warfarin in the prevention of stroke and thromboembolic complications of AF, with the advantage of less hemorrhagic stroke and intracranial bleeding. While these trial data are extremely encouraging, several practical issues (e.g., lack of specific antidote, safety of long-term treatment or cost-effectiveness in "real-life" clinical practice) still need to be elucidated.

Topics: Anticoagulants; Atrial Fibrillation; Drugs, Investigational; Factor X; Fibrinolytic Agents; Humans; Morpholines; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet-vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Humans; Male; Platelet Aggregation Inhibitors; Risk; Stroke; Treatment Outcome; Vitamin K

Venous thromboembolism (VTE) is a major public health concern since the incidence of VTE rises substantially with age. Furthermore, the diagnosis can be elusive since patients can present differently, causing delay in diagnosis and initiation of treatment and resulting in major morbidity and mortality. In addition to accuracy and precision in diagnosis, antithrombotic therapies are the cornerstones of VTE management. In traditional paradigm, vitamin K antagonists (warfarin), indirect factor Xa inhibitors, and heparin are the foundation in management of VTE. Warfarin has been the only available oral anticoagulant therapy for several decades. Although warfarin is effective in both treatment and prophylaxis against VTE, there are several limitations. Therefore, the novel anticoagulation therapies, including rivaroxaban, apixaban, and dabigatran etexilate, have apparent advantages over warfarin in terms of clinical efficacy and adverse effects. The objective of this review is to describe the background and clinical implications of these novel anticoagulants.

Topics: Acute Coronary Syndrome; Administration, Oral; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

Venous thromboembolism (including deep vein thrombosis and pulmonary embolism) and atrial fibrillation are common conditions in Western countries. The mainstay of treatment and prevention for these diseases is fast-acting anticoagulant drugs such as heparins and vitamin K antagonists. The use of these drugs is, however, complex and demanding for both patients and physicians. Recently, new antithrombotic drugs that act directly by inhibiting activated coagulation factors such as factor X or thrombin have been developed and investigated in phase III clinical trials. The aim of this article is to review: (i) the need to develop new drugs; (ii) their efficacy/safety as demonstrated in clinical trials; (iii) the need for laboratory monitoring and (iv) the direction towards the use of these new drugs in the real-life clinical situation.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Drugs, Investigational; Heparin; Humans; International Normalized Ratio; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Clinical Trials as Topic; Follow-Up Studies; Heart Atria; Humans; Prostheses and Implants; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is estimated that 1 in 4 individuals aged 40 years or above will develop at least 1 episode of AF during their lifetime. Stroke is a leading cause of serious, long-term disability and death, and a major socioeconomic burden in developed countries. The major risk factor for thromboembolic stroke is AF. Oral antithrombotic treatment for AF patients has been limited to vitamin K antagonists for more than 60 years. Treatment with warfarin can reduce, but fails to abolish thromboembolic stroke associated with AF. Despite anticoagulation, patients with AF are at increased stroke risk. Furthermore, warfarin has important limitations namely, the limited time in therapeutic range, the need for INR monitoring, risk of major bleeding including stroke, and drug interactions. Recently there have been very exciting and important new advances in thromboprophylaxis for AF. Novel oral agents have been developed and evaluated clinically. These include direct thrombin inhibitors (dabigatran etexilate), oral selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and PAR-1 inhibitors (vorapaxar and atopaxar). Some of the new drugs have demonstrated promising results in the clinical studies, they are convenient in use and do not require monitoring. The downsides are lack of antidotes or specific blood assays to monitor the anticoagulant effect. This review evaluates traditional and novel approaches to thromboprophylaxis in patients with AF.

Topics: Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Receptor, PAR-1; Vitamin K

The prevalence of atrial fibrillation is increasing because of an aging population. Vitamin K antagonists have been the standard therapy for stroke prevention in atrial fibrillation but are underutilized and often poorly managed because of their inherent limitations. This study critically reviews the recently completed phase 3 randomized controlled trials of new oral anticoagulants (OACs) for stroke prevention in patients with nonvalvular atrial fibrillation: RE-LY (dabigatran), AVERROES (apixaban), ARISTOTLE (apixaban) and ROCKET-AF (rivaroxaban).. On the basis of their favorable pharmacological characteristics and excellent efficacy and safety profile as demonstrated by the results of the randomized controlled trials, the new OACs have the potential to replace vitamin K antagonists as the first-line treatment for stroke prevention in atrial fibrillation, with warfarin reserved for patients with contraindications to the new OACs and those unable to afford them.. The new OACs represent a major advance for patients with atrial fibrillation with the potential to reduce morbidity and mortality due to cardioembolic stroke.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Platelet Aggregation Inhibitors; Prevalence; Randomized Controlled Trials as Topic; Stroke; United States; Vitamin K; Warfarin

Stroke is the most common cardiovascular disorder after heart disease, with a high mortality and often poor quality of life in survivors. Atrial fibrillation (AF), the most commonly occurring sustained cardiac arrhythmia increases the risk of stroke by five. However, stroke risk is not homogeneous and varies with associated morbidities and risk factors. Risk assessment scores have been developed and according to the calculated level of risk, guidelines recommend treatment with antithrombotic agents, preferably vitamin K antagonists (VKA). Despite these recommendations many patients with AF do not receive adequate thromboprophylaxis. The presence of AF is often not recognized and VKA are underused due to doctor- or patient-related factors and intrinsic disadvantages of these drugs. An awareness campaign for the diagnosis of AF is warranted, highlighting the risk of stroke. Novel anticoagulants that largely overcome many of the limitations of vitamin K antagonists are becoming available.

Topics: Antifibrinolytic Agents; Atrial Fibrillation; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Vitamin K

The prevention of thromboembolism is the main therapeutic goal in patients with atrial fibrillation (AF). Vitamin K antagonists have been proved highly effective in preventing thromboembolic events in patients with AF and despite recent advances in oral anticoagulation they remain the most widely used agents. Anticoagulation increases the incidence of bleeding; however, in the field of stroke prevention in AF the clinical benefit of vitamin K antagonists clearly outweighs potential risks. The annual incidence of major bleeding among individuals with AF on oral anticoagulation varies widely, ranging from 1.3% to 7.2%. Several factors affect bleeding risk including the intensity of anticoagulation, the efficacy of monitoring modalities, and patient characteristics. This multifactorial etiology makes prediction of bleeding risk complex, necessitating the derivation and validation of clinical prediction tools for the estimation of total bleeding risk in clinical practice. The present review summarizes data on definition, risk prediction, prevention, and management of oral anticoagulation‑associated bleeding as reflected by the recent European Heart Rhythm Association consensus statement.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Europe; Hemorrhage; Humans; Incidence; Patient Preference; Practice Guidelines as Topic; Risk Management; Societies, Medical; Stroke; Thromboembolism; Vitamin K

Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Drug Monitoring; Fibrinolytic Agents; Heart Diseases; Humans; International Normalized Ratio; Intracranial Embolism; Primary Prevention; Risk; Secondary Prevention; Stroke; Thrombophilia; Vitamin K

Stroke and atrial fibrillation (AF) constitute a true vascular epidemic with catastrophic consequences. The most common and devastating complication of AF is cardioembolic stroke but this catastrophic event can be predicted and prevented. Accurate etiologic diagnosis of stroke is essential for effective prevention. The percentage of cryptogenic ischemic strokes is too high and detection of AF and other causes of cardioembolic events should be improved. Cardioembolic cerebral ischemia can be prevented. However, because of physician inertia, lack of patient adherence and the problems of vitamin K antagonists, many patients are at risk of cerebral ischemia. Recently, major advances with drugs such as dronedarone, dabigatran and FXa inhibitors have opened the way to improving stroke prevention, as reflected in therapeutic guidelines, and neurologists should be familiar with these drugs. There is reason to hope that much suffering can be avoided.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Brain Ischemia; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Intracranial Embolism; Multicenter Studies as Topic; Prevalence; Randomized Controlled Trials as Topic; Risk Factors; Single-Blind Method; Thrombophilia; Vitamin K

New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Vitamin K; Warfarin

Oral anticoagulation with vitamin k antagonists (VKAs) requires regular testing and dose adjustment. Home-monitoring (self-testing or self-management) is more effective than usual management. Dabigatran, does not require dose-adjustment and appears to be more effective at reducing the risk of stroke with similar risks of bleeding in patients with atrial fibrillation (AF). Dabigatran, however, has not been compared to the home-monitoring. It was the objective to evaluate the efficacy of dabigatran compared with home-monitoring of oral anticoagulation with VKAs. Randomised controlled trials (RCTs) comparing usual management of oral anticoagulation with home-monitoring, dabigatran with usual management, and RCTs comparing dabigatran with home-monitoring and including patient-important outcomes (thromboembolic events, death and major bleeding) were eligible. For our direct comparison we calculated pooled relative risks (RRs) using the Mantzel-Haenzel random effect model. For the indirect comparison we estimated lnRRs and back transformed to RR. We evaluated the quality of the evidence with the GRADE system. Dabigatran, compared with warfarin, was associated with lower rates of stroke or thromboembolism and systemic embolism but similar rates of major haemorrhage and death. Dabigatran 150 mg also increased non-significantly the rate of myocardial infarction. The quality of the evidence was high. Our indirect comparison of home-monitoring of oral anticoagulation versus dabigatran showed no convincing differences in the risk of thromboembolism, death or major bleeding. The estimates for self-management vs. dabigatran showed stronger but still non-significant trends. The quality of the evidence was low. In conclusion, the indirect comparison of home monitoring of oral anticoagulation with dabigatran suggests that the treatments have similar impact on thrombosis, bleeding and death. However, the confidence in the estimate of effect is low to very low. Our analyses contrast with the available comparison of dabigatran with conventional warfarin monitoring.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Monitoring; Hemorrhage; Humans; Monitoring, Ambulatory; Self Care; Stroke; Thromboembolism; Vitamin K; Warfarin

For many decades Vitamin K antagonists were the standard orally given medication for primary and secondary prevention of thromboembolism in patients with atrial fibrillation and stroke. Three compounds, dabigatran, rivaroxaban, and apixaban, are now challenging this well established prescription, as they showed similar effect in preventing thromboembolism with a lower bleeding rate in recently published well designed, controlled randomised, non-inferiority trials. Their advantages of each are to have a fixed dosage, no need to monitor coagulation factors, and fewer interactions with food and other drug intake. The therapeutic effect is estimated overall similar between the three compounds. Who is a candidate for one of the new drugs: Patients with atrial fibrillation and the clear indication to get a future oral anticoagulation are potential candidates to receive one of the new drugs. Further this may be patients where the treatment with Vit K antagonists was difficult to optimise, patients who are not willing to have blood controls done regularly or where blood controls are difficult to obtain. This will also be an option in patients who had a stroke due to atrial fibrillation and had no history of cerebral bleeding. Who should not receive the new anticoagulants: patients who present stable blood coagulation values in the treatment range and no complications should not be merged to the new drugs. Patients with severe renal insufficiency or receiving a medication that interacts with the new drugs (e. g. ketoconazole) or with synthetic heart valves will not be candidates to receive the new drugs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; International Normalized Ratio; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Thromboembolism; Vitamin K

Atrial fibrillation (AF) has a prevalence of about 1% in the general population, but is much more common in the elderly. The annual overall risk of stroke is about 4.5% without antithrombotic therapy, but the risk in an individual patient varies from under 1% to about 20%, depending on the presence of well‑recognized risk factors. The risk of stroke, usually followed by major neurological deficit or death, is reduced by about two‑thirds by oral vitamin K antagonist (VKA) therapy and about 20% by aspirin. This risk reduction generally outweighs the risk of major hemorrhage caused by oral anticoagulation. New oral anticoagulants (dabigatran, rivaroxaban, and apixaban) obviate many of the difficulties experienced by patients and doctors in the use of oral VKAs. Comparisons with warfarin in recent large randomized clinical trials have demonstrated advantages of efficacy and safety, which vary somewhat from one agent to another but all offer excellent alternatives to VKAs for stroke prevention. Recent clinical practice guidelines recommend these agents as alternatives to VKAs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Canada; Clinical Protocols; Female; Humans; Male; Middle Aged; Risk Assessment; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Stroke; Vitamin K

We performed a systematic review of the available evidence on the relationship between the individual clinical, echocardiographic and laboratory characteristics of patients with atrial fibrillation (AF) and the risk of stroke. A systematic review was also performed of all published stroke risk stratification models, as well as the accuracy of their discriminative ability between risk strata. Third, we reviewed the literature on cost-effectiveness analyses with oral anticoagulation in AF. From the systematic review on stroke risk factors, a prior stroke or transient ischemic attack (15/16 studies positive, risk ratio [RR] 2.86), hypertension (11/20 studies positive, RR 2.27), aging (9/13 studies positive, RR 1.46 per decade increase), structural heart disease (9/13 studies positive, RR 2.0) and diabetes (9/14 studies positive, RR 1.62) were found to be good independent predictors of stroke. Supportive evidence was found for sex (8/22 studies positive, RR 1.67), vascular disease (6/17 studies positive, RR 2.61) and heart failure (7/18 studies positive, RR 1.85). The various risk stratification schemes classified variable proportions as low, moderate and high risk, but the CHA(2)DS(2)-VASc score classified the smallest proportion of patients as 'low risk'. Anticoagulation with vitamin K antagonists and dabigatran is cost-effective in patients at high risk of stroke, but not in patients without any other stroke risk factor beside AF. Continued efforts are warranted to improve the antithrombotic management of AF patients to identify, and challenge, risk factors and refine risk stratification models in order to realize an individualized tailored, risk factor-based approach.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Vitamin K

The incidence and prevalence of atrial fibrillation are quickly increasing, mainly due to the ageing of the population. Atrial fibrillation is, to date, a problem of public health. Atrial fibrillation is associated to a five-fold risk of stroke, which may be identified by score risks, such as CHADS(2) score. The classical antithrombotic treatment of atrial fibrillation is based on vitamin K antagonists. Trials made in the 90's have clearly shown that vitamin K antagonists were able to decrease stroke risk by about 60%. New oral anticoagulants are now available on the market to treat patients with atrial fibrillation. These drugs are dabigatran which has demonstrated an interest in the RE-LY trial. Two doses may be prescribed, 110 mg bid and 150 mg bid. Anti Xa have also demonstrated an interest : rivaroxaban in the ROCKET AF trial and apixaban in the AVERROES (versus aspirin) and ARISTOTLE trials. In the future these drugs will have a major place in the armamentarium used to treat patients with atrial fibrillation. In all these trials a decrease in intra cranial haemorrhages has been demonstrated. In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Kidney; Morpholines; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K

Novel oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Individually, NOACs were at least noninferior to vitamin K antagonists, but a clear superiority in overall and vascular mortality was not consistently proven.. We performed a meta-analysis of phase II and phase III randomized, controlled trials comparing NOACs with vitamin K antagonists in patients with atrial fibrillation. The MEDLINE and EMBASE databases, supplemented with conference abstract books and www.clinicaltrials.gov, were searched up to the first week of July 2012 with no language restriction. Two reviewers performed independent article review and study quality assessment. Data on overall and cardiovascular mortality, stroke or systemic embolism, ischemic stroke, major and intracranial bleeding, and myocardial infarction were collected. NOACs were pooled to perform a comparison with vitamin K antagonists, calculating pooled relative risks (RRs) and associated 95% confidence intervals (CIs). We retrieved 12 studies (3 administering dabigatran, 4 administering rivaroxaban, 2 administering apixaban, and 3 administering edoxaban) enrolling a total of 54 875 patients. NOACs significantly reduced total mortality (5.61% versus 6.02%; RR, 0.89; 95% CI, 0.83-0.96), cardiovascular mortality (3.45% versus 3.65%; RR, 0.89; 95% CI, 0.82-0.98), and stroke/systemic embolism (2.40% versus 3.13%; RR, 0.77; 95% CI, 0.70-0.86). There was a trend toward reduced major bleeding (RR, 0.86; 95% CI, 0.72-1.02) with a significant reduction of intracranial hemorrhage (RR, 0.46; 95% CI, 0.39-0.56). No difference in myocardial infarction was observed.. NOACs are associated with an overall clinical benefit compared with vitamin K antagonists. Additional research is required to confirm these findings outside the context of randomized trials.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Male; Middle Aged; Risk Factors; Stroke; Treatment Outcome; Vitamin K

To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin.. We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies.. Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032-0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139).. In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Humans; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Stroke; Vitamin K; Warfarin

Medical management of patients with atrial fibrillation (AF) at high risk for stroke is limited by problems of imperfect tools for assessment of thromboembolism and bleeding risks. Improved instruments, such as the CHA₂DS₂VASc and HAS-BLED risk stratification scores, have been incorporated into European practice guidelines. Until recently, the most effective therapy for stroke prevention has been anticoagulation with a vitamin K antagonist, but new oral anticoagulants in development, antiarrhythmic drugs that reduce adverse cardiovascular events in patients with AF, and interventional techniques for occlusion of the left atrial appendage represent promising options for stroke prevention. These new strategies will need focused evaluation in the most challenging AF patients-those with a high risk of bleeding, prior thromboembolism, or thrombosis-prone surfaces such as mechanical heart valve prostheses or drug-eluting coronary stents, for whom the limitations of currently available treatment options and a paucity of data are particularly acute.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Health Status Indicators; Humans; Risk Assessment; Stroke; Vitamin K; Warfarin

Stroke prevention in atrial fibrillation is of paramount importance given its associated morbidity and mortality. The many challenges of warfarin limit its effective use in real-world clinical practice. We are entering an exciting therapeutic era as new classes of anticoagulants, including direct thrombin inhibitors, factor Xa inhibitors and novel vitamin K antagonists, are being evaluated for possible use in this patient population. If proven to be as efficacious as warfarin and safer, expanded use of these novel agents to lower risk subgroups may be justified. It is imperative that providers be aware of the many advantages and potential challenges posed by use of these novel agents in routine clinical care. An understanding of individual pharmacokinetic profiles and potential drug-drug and drug-disease interactions will translate into improved effectiveness in real-world practice.

Topics: Administration, Oral; Anticoagulants; Antithrombins; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Drug Interactions; Factor Xa Inhibitors; Half-Life; Humans; Preventive Medicine; Risk Factors; Stroke; Vitamin K; Warfarin

The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran was shown in a large phase III trial to be more effective and safer than warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and has recently been approved for this indication. Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice.

Topics: Acute Coronary Syndrome; Amidines; Anticoagulants; Atrial Fibrillation; Azetidines; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombin; Thromboembolism; Treatment Outcome; Vitamin K

Vitamin K antagonists (VKAs) are the main therapeutic agents used to prevent embolic events in patients with atrial fibrillation (AF). Despite their proven efficacy, VKAs are underused and have several limitations. In recent years, there has been great interest in the development of new oral anticoagulants with a more efficient pharmacological profile, first tested in venous thromboembolism prevention and later in AF.. The authors review the pharmacological differences between dabigatran, rivaroxaban and apixaban, and potential subgroups of patients in whom these new drugs would constitute a possible alternative to VKA therapy. Pharmacodynamic and pharmacokinetic data from each compound are analyzed in respect to their potential use in AF. This article provides an exhaustive review of the current status of this topic and the controversies still regarding each drug.. Apixaban and rivaroxaban are under evaluation for thromboembolic prevention in AF; dabigatran was recently approved for this indication. Therefore, it is important to know the characteristics of these drugs as a potential alternative to VKAs.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Design; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; Vitamin K

Cerebral infarction is the most serious complication of atrial fibrillation. Coumarin derivatives (vitamin K antagonists) counteract systemic thromboembolism and reduce the risk of stroke by more than 60%, but carry a risk of serious bleeding. Antiplatelet therapy and subcutaneous low-molecular-weight heparin are as yet not sufficiently effective and are associated with a bleeding risk similar to vitamin K antagonists. Vitamin K antagonists require intensive INR monitoring to ensure efficacy and safety. In the past decade, oral agents have been developed that directly inhibit the activity of thrombin (factor IIa) and of activated factor X (Xa), which is the first compound in the final common pathway of the coagulation cascade. These do require INR monitoring and have rapid onset and offset of action. The first results with thrombin blockers, such as dabigatran, look promising in efficacy and safety and Xa inhibitors are currently under investigation in atrial fibrillation in 3 large clinical trials. Long-term safety of the new agents in patients with atrial fibrillation has not yet been determined.

Topics: Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation; Humans; International Normalized Ratio; Platelet Aggregation Inhibitors; Stroke; Thrombin; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Evidence-Based Medicine; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Stroke; Thrombin; Thromboembolism; Vitamin K; Warfarin

Dabigatran etexilate is the first oral anticoagulant to be approved in the United States in decades. It works directly by inhibiting clot-bound and free factor IIa (ie, thrombin) and indirectly by inhibiting platelet aggregation induced by thrombin. It is approved in the United States for stroke prophylaxis in nonvalvular atrial fibrillation. There is evidence to suggest that it is also effective for the treatment of acute venous thromboembolism and venous thromboembolism prophylaxis after knee and hip replacement surgery. Dabigatran etexilate therapy does not require laboratory monitoring, an advantage over warfarin. Unlike the earlier direct thrombin inhibitor, ximelagatran, it has demonstrated no potential for serious hepatotoxicity. It is also subject to a much lower degree of interpatient variability in dose response, has no diet-drug interactions, and has fewer clinically significant drug-drug interactions compared with warfarin. Dabigatran etexilate appears to be a valuable addition to our anticoagulant armamentarium.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement; Atrial Fibrillation; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drug Interactions; Heparinoids; Humans; Pulmonary Embolism; Pyridines; Stroke; Venous Thromboembolism; Vitamin K

Anticoagulant therapy in patients with atrial fibrillation requires careful evaluation because its benefits i.e. prevention of thromboembolism, must be greater than the risk of bleeding. Patients at higher risk of thrombosis are evaluated through specific scores, such as the CHA(2)DS(2)VASc, coupled with scoring systems for assessing bleeding risks, such as the HAS-BLED score. In addition to bleeding, other risks have been associated with the use of warfarin, including an increased susceptibility to vascular calcifications and fractures caused by a reduction in the levels of vitamin K dependent carboxylated enzymes, matrix Gla-protein (MGP) and bone Gla-protein or osteocalcin (BGP). In fact, while on one side warfarin is used to prevent embolism, on the other hand acting as a vitamin K antagonist it blocks the inhibitory effect of MGP on vascular calcification. Similarly, patients treated with warfarin carry a greater risk of developing osteoporosis and fractures, due to reduced BGP activity. Recently, a new generation of anticoagulant drugs has been developed, such as dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct factor-Xa inhibitor. They offer an interesting alternative to warfarin, because they do not require frequent blood tests for monitoring while offering similar results in terms of efficacy. Lacking the inhibitory effect on the vitamin K cycle, the consequent side effects can be avoided. If, compared to warfarin treated patients, a lower incidence of vascular calcifications and fractures will be demonstrated, the advantages over warfarin may be even greater, leading to further benefits in terms of morbidity and mortality.

Topics: Animals; Anticoagulants; Atrial Fibrillation; Drug Design; Drug Monitoring; Hemorrhage; Humans; Spinal Fractures; Thromboembolism; Vascular Calcification; Vitamin K; Warfarin

Atrial fibrillation (AF) is a large public health problem that affects about 1% of the population in the United States. It confers an increased risk for stroke and thromboembolism, but the stroke risk is not equal in all patients. Further refinement in stratifying stroke risk in patients with AF will help in properly directing therapy for AF patients while minimizing adverse events. Warfarin is the first-line treatment for stroke reduction in patients with AF, but many new drugs are on the horizon that will significantly change practice. New and improved cardiac monitoring techniques and devices will help with detection of AF in those at risk for stroke and will assist in assessing which patients will most benefit from anticoagulation.

Topics: Anticoagulants; Antithrombins; Atrial Appendage; Atrial Fibrillation; Defibrillators, Implantable; Electrocardiography; Factor Xa Inhibitors; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stroke; Telemetry; Vitamin K

Prevention of atrial fibrillation-related stroke is an important part of atrial fibrillation management. However, stroke risk is not homogeneous and varies with associated morbidities and risk factors. Risk stratification schemes have been developed that categorize patients' stroke risk into classes based on a combination of risk factors. According to the calculated level of risk, guidelines recommend patients with atrial fibrillation receive antithrombotic therapy either as a vitamin K antagonist or aspirin. Despite recommendations, however, many patients with atrial fibrillation do not receive adequate thromboprophylaxis. We will discuss some of the underlying reasons, in part related to the drawbacks associated with vitamin K antagonists. These highlight the need for new anticoagulants in atrial fibrillation. The novel oral anticoagulants in development may overcome some of the limitations of vitamin K antagonists and address their underuse and safety concerns.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antithrombins; Aspirin; Atrial Fibrillation; Contraindications; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Drugs, Investigational; Factor Xa Inhibitors; Fibrinolytic Agents; Guideline Adherence; Humans; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Vitamin K

Strokes and transient ischaemic attacks in patients with atrial fibrillation (AF) can be largely prevented. Risk stratification and appropriate prophylactic regimens help to alleviate the burden of AF-related thromboembolism. Guidelines recommend routine anticoagulation with oral vitamin K antagonists (VKAs) for patients at moderate-to-high risk of stroke, and acetylsalicylic acid (ASA) for those at low risk of stroke. ASA is less effective at reducing the risk of stroke than VKAs; however, ASA does not require monitoring or dose adjustment. Trials of anticoagulants show consistent benefits of oral VKAs for primary and secondary stroke prevention in patients with AF. Nevertheless, VKAs do require frequent coagulation monitoring and dose adjustment because of their variable dose-response profile, narrow therapeutic window, increased risk for bleeding complications and numerous food and drug interactions. This review aims to provide an overview of the clinical challenges of anticoagulant therapy for the prevention of stroke in patients with AF.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Drug Monitoring; Humans; Stroke; Vitamin K

Atrial fibrillation (AF) confers an increased risk of ischemic stroke or thromboembolism that is reduced by long-term oral anticoagulant therapy. Until recently, the latter has typically been one from the vitamin K antagonist (VKA) class of drugs. Although highly effective, VKAs have limitations, and their use is challenging for both patients and clinicians. A new generation of oral anticoagulant drugs is emerging, including several drugs that appear to be viable alternatives to VKAs in AF patients.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Humans; Vitamin K

Dabigatran is an oral direct thrombin inhibitor with a rapid onset. Patients on dabigatran do not require coagulation monitoring. Recent prospective randomized trials have shown the efficacy of dabigatran for the prevention of venous thromboembolism after knee or hip arthroplasty and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Because dabigatran is cleared principally by the kidneys, dosage adjustments are required in the setting of renal dysfunction. There currently is no reversal agent for dabigatran although hemodialysis can facilitate its rapid removal in life-threatening circumstances. The management of severe bleeding associated with dabigatran also may include the administration of a procoagulant, such as recombinant activated factor VII. Based on recent guidelines, regional anesthesia should be used cautiously in patients taking this novel oral thrombin inhibitor.

Topics: Anesthesia, Conduction; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Chemistry, Pharmaceutical; Dabigatran; Fondaparinux; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Thrombin; Venous Thromboembolism; Vitamin K

Vitamin K antagonists and heparins have been standard anticoagulation drugs over the past decades. They are effective and safe but they have several drawbacks which has led to the development of new oral anticoagulants. Dabigatran etexilate is a specific oral thrombin inhibitor and rivaroxaban and apixaban are oral inhibitors of factor Xa. These agents produce a predictable anticoagulant response after fixed-dose administration so that routine coagulation monitoring is unnecessary. Currently, dabigatran etexilate, rivaroxaban and apixaban are licensed for thromboprophylaxis after elective total hip or knee replacement surgery. Since august 2011, dabigatran etexilate is licensed for patients with atrial fibrillation, rivaroxaban will follow. However, indications will be expanded e.g. for therapy of venous thromboembolism. It is important to be aware of the pharmacokinetic and pharmacodynamic profiles of these new agents. The drugs considerably influence the global test of coagulation thus making an interpretation of test results difficult. Currently, there is a lack of suitable coagulation tests to monitor anticoagulation in emergency cases, such as bleeding. Specific antidotes are not yet available.

Topics: Administration, Oral; Antithrombins; Arthroplasty, Replacement, Hip; Atrial Fibrillation; Benzimidazoles; Blood Coagulation Tests; Critical Care; Dabigatran; Drug Approval; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

Arial fibrillation (AF) is the most commonly occurring sustained arrhythmia in the United States and is associated with increased mortality. AF is a risk factor for ischemic stroke, and risk factors for AF include comorbid conditions such as congestive heart failure, diabetes mellitus, older age, hypertension, diabetes, pulmonary disease, and history of stroke, transient ischemic attack, or heart failure. Risk stratification for ischemic stroke in AF patients is based on scoring a group of risk factors that allows for the appropriate tailoring of antithrombotic therapy. The vitamin K antagonists are effective at reducing ischemic stroke rates in medium-risk to high-risk patients and are therefore generally recommended for this group. However, a large proportion of these patients are not treated with vitamin K antagonists because of the potential for adverse outcomes, particularly in elderly patients. New direct thrombin inhibitors and direct Factor Xa inhibitors in development offer the possibility of simplifying treatment and management although offering similar or better efficacy and safety profiles to warfarin. In light of these potential new treatments, the importance and improvement of risk stratification methods and the resulting recommendations in thromboprophylaxis become even more paramount as they make it more likely that medium-risk to high-risk patients can be treated safely.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Chemoprevention; Comorbidity; Diabetes Mellitus; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Failure; Humans; Risk Factors; Stroke; Vitamin K

Long-term anticoagulation with a vitamin K antagonist (VKA) or the new agent dabigatran is recommended to decrease stroke risk in patients with atrial fibrillation. When patients with atrial fibrillation undergo initiation or interruption of VKA therapy, or experience an isolated subtherapeutic international normalized ratio (INR), bridge therapy with a parenteral anticoagulant may be considered. To describe the literature for anticoagulation bridge therapy in patients with atrial fibrillation, we conducted a MEDLINE search (1966-February 2011) of the English-language literature to identify related studies. Ongoing clinical trials were identified through a search of the ClinicalTrials.gov registry. Major national and international guidelines were gathered and evaluated. Additional literature was obtained through review of relevant references of the identified articles. Bridging is not supported by guidelines or clinical trials for patients starting VKA therapy for atrial fibrillation. A subtherapeutic INR value during long-term VKA therapy may be associated with increased thromboembolic events, but the benefit of bridging has not been demonstrated. When VKA therapy is interrupted for procedures, retrospective and cohort data suggest that the decision to bridge should be based on a patient's thromboembolic and bleeding risks associated with the procedure. Typically, it is recommended to use bridge therapy in patients with atrial fibrillation at high risk for thromboembolism, but the benefit of bridging is less clear in patients at low risk. Not all procedures necessitate anticoagulation interruption. Recent trials suggest that VKAs can be continued when patients are undergoing cardiac device procedures and some types of radiofrequency ablation. Several clinical trials are ongoing that will provide more definitive guidance for perioperative anticoagulation management of patients with atrial fibrillation. Patients taking dabigatran are unlikely to require bridge therapy because of a predictable anticoagulant effect and rapid onset of action. However, evidence for optimal perioperative management of dabigatran is needed.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; International Normalized Ratio; Perioperative Care; Stroke; Thromboembolism; Vitamin K

There remains uncertainty over optimal antithrombotic management strategy for patients with atrial fibrillation (AF) presenting with an acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Clinicians need to balance the risk of stroke and thromboembolism against the risk of recurrent cardiac ischaemia and/or stent thrombosis, and the risk of bleeding. This consensus document comprehensively reviews the published evidence and presents a consensus statement on a 'best practice' antithrombotic therapy guideline for the management of antithrombotic therapy in such AF patients.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Atrial Fibrillation; Benchmarking; Evidence-Based Medicine; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Patient Selection; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recurrence; Risk Assessment; Risk Factors; Stents; Stroke; Thrombosis; Treatment Outcome; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1% of adults; its prevalence increases with age. Nine percent of those aged 80 years and older have AF. AF is associated with increased cardiovascular mortality and morbidity, and the risk of stroke ist increased by the factor 5. Stroke in patients with AF is more severe and more likely to be fatal. Prevention of thromboembolism with oral anticoagulants and rate- or rhythm-control are the main therapeutic strategies for patients with AF. But vitamin K antagonists, which reduce the risk of stroke in patients with AF, are underutilized. Until recently, rhythm-control studies did not show any benefit in the prevention of cardiovascular complications, including stroke. New drugs have recently become available that may add to the therapeutic options. A post-hoc analysis of dronedarone, a novel antiarrhythmic drug, suggests a reduction of the risk of stroke by 34% (p = 0.027) in patients with non-permanent atrial fibrillation in addition to standard therapy, including antithrombotics. The novel anticoagulant dabigatran showed stroke reductions and improved safety in the RE-LY trial which compared its efficacy with warfarin. On-going studies will help to identify those patients with AF who are likely to benefit from these novel antithrombotic and antiarrhythmic agents by reducing the risk of stroke.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dronedarone; Drug Therapy, Combination; Humans; Pyridines; Risk Factors; Stroke; Survival Rate; Thrombin; Vitamin K

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. The prevalence and incidence of AF are rising, as confirmed in several European and American registries. Guidelines published in 2008 from the European Society of Cardiology/American Heart Association and from the American College of Chest Physicians, clarified the strategy of antithrombotic treatment in AF, which is based on the presence of risk factors for thromboembolism. This approach allows physicians to classify patients as at low, moderate or high risk, according to their individual risk characteristics, which are relatively similar in both sets of recommendations. Patients at moderate risk, however, who might justify anticoagulant or antiplatelet treatment, could be better characterized using morphological (echocardiographic) and/or biological factors or risk markers. Recent data have shown that the existence of a thrombogenic milieu in the left atrium (e.g., dilatation of the left atrial appendage and/or thrombus and/or spontaneous echocontrast and/or reduced emptying/filling flow velocity) indicates a higher risk of embolism and mortality. Furthermore, high-sensitivity C-reactive protein and haemostasis markers of coagulation are associated with thromboembolic risk and excess mortality in AF. Although current recommendations for the management of AF are not based on such markers, both could help physicians choose the optimal antithrombotic treatment (either vitamin K antagonists or antiplatelet drugs) according to the patient's specific risk profile. Nowadays, registries confirm under-prescription of vitamin K antagonist treatment in the 'real world,' even in patients at high thromboembolic risk, and over-prescription for at least one-third of low-risk patients. It is crucially important to realize that the risk of bleeding in patients with risk factors (e.g., older age, hypertension) is close to the risk of thromboembolism, which can have devastating outcomes in patients in AF. Alternative and efficient strategies (new oral anticoagulants, non-surgical closure of the left atrial appendage using percutaneous devices) are currently under investigation. Therefore reducing the risk of thromboembolism should be physicians' primary aim, particularly with the advent of alternative treatments and the development of new antithrombotic drugs such as oral thrombin and factor Xa inhibitors, which are currently being evaluated in clinical trials.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Risk Factors; Thromboembolism; Vitamin K

Surgical replacement of a native valve with a biological or mechanical prosthesis is the definitive treatment for many forms of advanced valvular heart disease. Mechanical heart valves are less prone to structural deterioration compared with bioprostheses, but require chronic oral anticoagulation to prevent thromboembolic events. Thromboembolic risk varies based on patient-related risk factors, including atrial fibrillation, advanced age, low ejection fraction, and hypercoagulability. Other important correlates of high thromboembolic risk include valve design, valve position, anticoagulation variability, and time from surgery. Clinical management is further complicated when antithrombotics may need to be interrupted or altered during surgery or pregnancy. At present, vitamin K antagonists are the only approved agents for thromboprophylaxis but are limited because of a narrow therapeutic window and requirement for frequent monitoring. Novel anticoagulants, including inhibitors of factor IIa and Xa, are currently being evaluated and may emerge as alternatives to vitamin K antagonists.

Topics: Age Factors; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Risk Factors; Stroke Volume; Thromboembolism; Vitamin K

Arterial and venous thromboembolism account for significant morbidity and mortality worldwide. Warfarin, and other vitamin K antagonists (VKAs), have been the only class of oral anticoagulants currently in clinical use and have been so for over 50 years. Although warfarin is effective in preventing thromboembolism, its use is limited by its narrow therapeutic index that necessitates frequent monitoring and dose adjustments resulting in considerable inconvenience to patients and clinicians. There are now several orally administered anticoagulants in late stages of clinical development that may offer effective, safer, and more convenient anticoagulation. This review summarizes and compares data on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Stroke; Thrombin; Thromboembolism; Vitamin K; Warfarin

Warfarin is a commonly used medication for the prevention and treatment of venous thromboembolism. It can be challenging for both the patient and the prescriber to manage at times.. To describe the mechanism of action of warfarin, and to discuss the indications for warfarinisation, the risks associated with warfarin use, and some of its drug interactions.. The common indications for warfarinisation are atrial fibrillation, venous thromboembolism and prosthetic heart valves. Contraindications include absolute and relative contraindications, and an individualised risk-benefit analyses is required for each patient. There are many interactions with warfarin, including pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions can be monitored by using International Normalised Ratio levels. Pharmacodynamic interactions require knowledge by the prescriber to predict any interactions with warfarin, and International Normalised Ratio monitoring assists.

Topics: Anticoagulants; Atrial Fibrillation; Cytochrome P-450 Enzyme System; Drug Interactions; Heart Valve Prosthesis; Humans; International Normalized Ratio; Risk Factors; Venous Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) is the most commonly occurring arrhythmia, and is a condition of both significant clinical and economic importance. An antithrombotic agent is considered mandatory as part of the management in most patients with AF. It has been conclusively demonstrated that long-term anticoagulation therapy can significantly reduce the risk of stroke in patients with nonvalvular AF. While vitamin K antagonists (VKAs) such as warfarin are highly effective, they possess numerous limitations that curtail their use, or make their use challenging for clinicians and patients. A new generation of anticoagulants are being investigated in phase III clinical trials in patients with AF. One or more of these agents have the potential to either replace or act as alternatives to VKA therapy in AF. This group includes the direct thrombin inhibitor, dabigatran, the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, and finally, the vitamin K analogue, tecarfarin. Additional agents are being developed in phase I or II clinical trials. The direct thrombin and factor Xa inhibitors are generally small, synthetic molecules with predictable pharmacokinetics, a predictable pharmacodynamic effect, few drug interactions and do not require routine therapeutic drug monitoring. These new anticoagulants may well represent a new era in anticoagulation. However, they do possess their own limitations and will present new challenges for clinicians.

Topics: Atrial Fibrillation; Blood Coagulation; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Stroke; Thrombin; Treatment Outcome; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice and is associated with an increased risk of stroke, mortality and significant morbidity. Given the rapidly increasing incidence and prevalence of AF, and the resulting public health burden of the consequences associated with this arrhythmia, stroke prevention is an extremely important topic.. This review covers the epidemiology of AF, the pathophysiology of ischemic stroke in AF and current antithrombotic therapy choices for stroke prevention in this condition. In addition, this article discusses important topics such as the assessment of stroke risk stratification and bleeding risk assessment, which are key issues in deciding upon thromboprophylaxis for AF patients. Finally, the review highlights the advent of new anticoagulant therapies and discusses the future challenges for researchers in this area.. This review summarizes all of the major antithrombotic trials conducted in AF patients over the last twenty years and highlights the importance of anticoagulation therapy for the prevention of stroke, after appropriate individual stroke and bleeding risk assessment.. Assessment of individual stroke risk and bleeding risk is key in determining appropriate thromboprophylaxis for AF patients, given the associated thromboembolic and hemorrhagic complications. The availability of newer, safer and more convenient drugs will mean that oral anticoagulation is available for a larger proportion of AF patients who may benefit from it.

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Stroke; Vitamin K

Many years of practical use and intensive scientific research have allowed vitamin K antagonists to become a cornerstone of treatment of internal diseases. Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K antagonists and the availability of new drugs in regard to a targeted anticoagulation therapy ask for a new review of the situation. Proof of effectiveness for the perioperative prophylaxis of venous thrombosis after hip and knee replacement has already been achieved for the direct thrombin inhibitor dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und apixaban compared to low molecular weight heparins. These new drugs are now also investigated in patients with internal diseases. For the long-term application (6 or 12 months) concerning the treatment of venous thrombosis and/or stroke prophylaxis in patients with atrial fibrillation data is already available for the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its effectiveness in comparison with vitamin K antagonists is equal or even better without disadvantages in safety. However, vitamin K antagonists will remain the standard oral anticoagulation until open questions regarding e.g. insufficient therapy adherence (with termination rates up to 20%) or problems with drug interactions of the new competitive products have been completely answered.

Topics: Anticoagulants; Antithrombin Proteins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis; Vitamin K

Antithrombotic/antiplatelet therapy after coronary stent implantation is recommended with a high level of evidence in international guidelines. However, antithrombotic/antiplatelet treatment in patients after coronary stent implantation and in addition with an indication for oral anticoagulation is still an open issue. So called "tripletherapy", the combination of oral anticoagulation with vitamin K-antagonists, clopidogrel and aspirin, is commonly used. This combination significantly increases incidence of minor and major bleedings, especially during long term use. The goal of this manuscript is to discuss the risks and potential benefit of "tripletherapy" in patients with an indication for oral anticoagulation after coronary stent implantation.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cross-Sectional Studies; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Factors; Stents; Stroke; Thrombosis; Ticlopidine; Vitamin K

Adverse drug events affect millions of patients each year. An important drug-drug interaction between amiodarone and vitamin K antagonists is encountered frequently in daily clinical practice. Warfarin, a commonly used anticoagulant, is a mixture of 2 optically active isomers (R and S enantiomers). The S enantiomer is approximately 3 times more potent than the R enantiomer and is metabolized primarily by CYP2C9. Inhibition of CYP2C9 by amiodarone and its major metabolite potentiates the anticoagulant effects of warfarin, increasing the risk of serious bleeding. In contrast, dronedarone, a synthetic derivative of amiodarone the structure of which lacks the iodine moiety, is less likely to cause a drug-drug interaction with warfarin. Accordingly, dronedarone may be a particularly attractive antiarrhythmic choice among patients with atrial fibrillation who are also being treated with warfarin.

Topics: Amiodarone; Anticoagulants; Atrial Fibrillation; Dronedarone; Drug Interactions; Drug Therapy, Combination; Humans; Vitamin K; Warfarin

Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important independent stroke risk factor, especially in the elderly. This article provides the reader with an overview as well as an update on primary and secondary stroke prevention strategies in patients with AF. Vitamin K antagonists remain the cornerstone therapy in AF patients at high risk of stroke. Both aspirin monotherapy and the combination of aspirin and clopidogrel are inferior to vitamin K antagonists in patients with AF. The new direct thrombin inhibitor dabigatran is at least as effective as warfarin and leads to a significant and clinically relevant decrease in hemorrhagic stroke and intracranial bleeds. Interventional therapies such as percutaneous closure of the left atrial appendage or radiofrequency catheter ablation have not yet been proven to decrease the stroke risk in patients with AF.

Topics: Aged; Animals; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Primary Prevention; Risk Factors; Secondary Prevention; Stroke; Vitamin K

Atrial fibrillation is the most common sustained rhythm disturbance. Thromboembolic events related to atrial fibrillation result in significant morbidity, mortality and increases in the cost of healthcare. Anticoagulants are pivotal agents for the prevention and treatment of thromboembolic disorders. The latest American College of Cardiology/American Heart Association guidelines recommend antithrombotic therapy to prevent thromboembolism for all patients with atrial fibrillation, except those with lone atrial fibrillation or contraindications. Vitamin K antagonists were first synthesized in 1948 and for the past six decades they have been the only agents used for long-term oral anticoagulant therapy. Although these drugs are effective, they have numerous limitations, which have led to the development of newer anticoagulant therapies. The emerging oral anticoagulant agents are target selective. They have predictable pharmacokinetic and pharmacodynamic parameters and do not require routine monitoring. They are not associated with significant food and drug interactions, and can be administered in simple fixed daily or twice daily doses. This article reviews the current literature on various targets for anticoagulant therapy and newer oral anticoagulants for atrial fibrillation.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Drug Delivery Systems; Drug Design; Humans; Practice Guidelines as Topic; Thromboembolism; Vitamin K

The review analyses various approaches to management of patients presenting with atrial fibrillation and having to take vitamin K agonists in order to prevent arterial thromboembolic complications in cases they develop exacerbations of their coronary hear disease and/or require transcutaneous coronary interventions. With the problem being insufficiently studied as yet, the majority of therapeutic decisions as to the most efficient and safe methods of administering antithrombotic agents in the clinical situations involved are made based on the results of follow up of the patients, the data regarding peculiarities of the action of therapeutic agents, and common sense. Presented herein are contemporary recommendations on long-term antithrombotic therapy in patients suffering from atrial fibrillation and taking vitamin K antagonists and subjected to coronary stenting.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Atrial Fibrillation; Coronary Disease; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Thromboembolism; Time Factors; Vitamin K; Warfarin

Topics: Angioplasty, Balloon, Coronary; Angiotensin II Type 2 Receptor Blockers; Anticoagulants; Atrial Fibrillation; Cardiology; Coronary Disease; Drug-Eluting Stents; Heart Diseases; Humans; Morpholines; Myocardial Infarction; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Cardioembolism accounts for approximately 20% of ischaemic strokes, and is associated with high mortality and propensity to recurrences. Approximately, 30% of ischaemic strokes remain cryptogenic despite improved imaging modalities and technological improvements to identify their cause. Of the long list of various cardiac conditions associated with an increased risk of cardioembolic strokes, non-valvular atrial fibrillation is the most common cause. Unsurprisingly, the stroke risk associated with these conditions is highly variable and non-homogenous, with many risk factors additive to the overall risk profile. Treatment with vitamin K-antagonists substantially reduces the long-term complications associated with cardioembolism in some high-risk patients, for example, in atrial fibrillation. Careful selection of antithrombotic drug regime needs to be carried out in patients individually to minimise the risk of bleeding encountered with such therapy. Apart from atrial fibrillation, there is relatively limited evidence for the role of antithrombotic therapy for other cardiac conditions associated with cardioembolism and how long one should treat.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Heart Diseases; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Myocardial Infarction; Stroke; Thrombosis; Vitamin K

Vitamin K antagonists are the only oral anticoagulants available and are considered as well-established treatment to prevent a first stroke or a recurrent stroke in patients with atrial fibrillation. The difficulties in the routine management of these patients cause an underuse of vitamin K antagonists. For long-term use, there is a need for safer and more effective oral anticoagulants that do not require routine monitoring of coagulation. Recently, new drugs have been developed and there are a number of clinical trials for the primary and secondary prevention of stroke in atrial fibrillation. The new anticoagulants that are being investigated target factor Xa or thrombin. The factor Xa inhibitors include indirect inhibitors such as idraparinux and biotinylated idraparinux that inhibit factor Xa by potentiating antithrombin. Also being investigated are apixaban and rivaroxaban, orally active agents that inhibit factor Xa directly. Direct thrombin inhibitors include ximelagatran and dabigatran etexilate. Although ximelagatran was withdrawn early because of liver toxicity, it provided convincing evidence that new oral anticoagulants have the potential to replace warfarin. However, even if these new drugs prove superior to dose-adjusted warfarin, their benefits must be substantial (retaining high efficacy with added safety and convenience) to offset their increased cost.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Factor Xa Inhibitors; Humans; Primary Prevention; Risk Assessment; Secondary Prevention; Stroke; Thrombin; Treatment Outcome; Vitamin K

Although warfarin and other vitamin K antagonists have clearly the greatest efficacy among treatments commonly available in preventing stroke in atrial fibrillation, their use is associated with a substantial risk of major bleedings and are unpractical and difficult to use because of their narrow therapeutic window, their interaction with drugs and foods, and the need of frequent coagulation monitoring. Several new anticoagulants are now undergoing phase III clinical trials in atrial fibrillation with the aim of demonstrating noninferiority compared with vitamin K antagonists or superiority compared with aspirin in patients in whom vitamin K antagonists are contraindicated or not tolerated. These drugs fall in different pharmacological categories of oral direct thrombin inhibitors, parenteral long-lived indirect factor Xa inhibitors, and oral direct factor Xa inhibitors. Cardiologists need to be aware of the explosive pharmacological literature being accrued with these new drugs, as most of these will likely enter the clinical arena in the near future.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coumarins; Drugs, Investigational; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Injections; Platelet Aggregation Inhibitors; Risk Assessment; Stroke; Thrombin; Thrombosis; Treatment Outcome; Vitamin K

Morbidity and mortality associated with atrial fibrillation are mainly related to thromboembolic complications, particularly ischemic strokes. The prevention of thromboembolism is an important component in the management of patients with atrial fibrillation. The choice of optimum antithrombotic therapy for a given patient depends on the risk of thromboembolism, on the one hand, and the risk of intracerebral hemorrhage, on the other hand. Concerning the benefit-to-risk stratification the problem lies in the similar and sometimes even identical risk factors for both thromboembolism and haemorrhage.At present, oral vitamin K antagonists are recommended for patients with atrial fibrillation at moderate or high risk of ischemic stroke. The thromboembolic risk should be assessed using validated stratification schemes, such as the CHADS(2) score. Aspirin alone is recommended for patients at low risk of thromboembolic complications. A combination of anticoagulant and antiplatelet drugs is necessary in patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation, but the optimal therapeutic management of these patients has not yet been defined. Hopefully, the development of new antithrombotic agents being easier to use and having a superior benefit-to-risk ratio will extend effective prevention of thromboembolic events to a greater part of the atrial fibrillation population at risk.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Drug Therapy, Combination; Fibrinolytic Agents; Heparin; Humans; Platelet Aggregation Inhibitors; Thromboembolism; Vitamin K

Atrial fibrillation is already the most common clinically significant cardiac arrhythmia and a common cause of stroke. Vitamin K antagonists are very effective for the prevention of cardioembolic stroke but have numerous limitations that limit their uptake in eligible patients with AF and reduce their effectiveness in treated patients. Multiple new anticoagulants are under development as potential replacements for vitamin K antagonists. Most are small synthetic molecules that target factor IIa (e.g., dabigatran etexilate, AZD-0837) or factor Xa (e.g., rivaroxaban, apixaban, betrixaban, DU176b, idrabiotaparinux). These drugs have predictable pharmacokinetics that allow fixed dosing without laboratory monitoring, and are being compared with vitamin K antagonists or aspirin in phase III clinical trials [corrected]. A new vitamin K antagonist (ATI-5923) with improved pharmacological properties compared with warfarin is also being evaluated in a phase III trial. None of the new agents have as yet been approved for clinical use.

Topics: Anticoagulants; Atrial Fibrillation; Benzamides; Benzimidazoles; Biotin; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Vitamin K

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice and is associated with substantial morbidity and mortality. Its prevalence increases with age, affecting about 1% of patients aged <60 years and almost 10% of patients >80 years. AF is associated with a fivefold increasing risk of embolism or stroke with absolute risk ranging from less than 1% to 20% per year, depending on patient age and the presence of clinical risk factors including congestive heart failure, systemic hypertension, diabetes mellitus and prior history of cardioembolic events. Vitamin K antagonists (VKAs) and acetyl salicylic acid are currently the only licensed antithrombotic therapies for stroke prevention in patients with AF. Anticoagulants are very effective for stroke prevention in patients with AF, overall a 64% relative risk reduction. Nonetheless, approximately 50% of patients with AF who have an indication for VKA receive anticoagulant therapy, of which only 50% maintain adequate therapeutic ranges. Furthermore, 50% will discontinue VKAs within 3 to 5 years regardless of appropriate international normalized ratio control. Underutilization of VKAs is related, in part, to their numerous limitations and difficulty in maintaining adequate therapeutic control, prompting the development of new antithrombotic strategies that are equally effective and safer, and easier to manage than VKAs. This review focuses on new antithrombotic therapies for stroke prevention in patients with AF.

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Randomized Controlled Trials as Topic; Stroke; Thrombin; Vitamin K

Atrial fibrillation (AF) can significantly increase morbidity and mortality. It is gaining in clinical and economic importance, being the most commonly encountered tachyarrhythmia in clinical practice. Stroke is the most serious complication. Evidence from AF antithrombotic treatment trials is reviewed, risk stratification of patients with AF is discussed, and recommendations for anticoagulation are presented.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Drug Combinations; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Stroke; Vitamin K; Warfarin

Stroke remains an increasing worldwide cause of disability and mortality, and it is the second leading cause of death in industrialized countries. Patients with atrial fibrillation form a unique group with increased risk of cardioembolic stroke. Despite the widespread application of the National Institutes of Health stroke scale and guidelines, patients with atrial fibrillation represent a clinically challenging group that deserves a special approach during the acute stroke phase. The mechanism of stroke in these patients is either cardioembolic [especially with an international normalized ratio (INR) < 2.0] or hemorrhagic (especially with INR > 5.0) (Figure 1). Atrial fibrillation with valvular heart disease significantly increases the risk for ischemic stroke. Specifically, patients with mitral stenosis who develop atrial fibrillation increase their risk of cardioembolism by 3 to 7 times. Many patients with atrial fibrillation still develop ischemic or hemorrhagic stroke despite appropriate use of anticoagulation. Prior stroke, transient ischemic attacks, congestive heart failure, hypertension, age > 75, and diabetes mellitus are all well-established risk factors for the development of stroke in patients with atrial fibrillation. The CHADS-2 score is the most widely studied and clinically used method for stratifying patients with nonrheumatic atrial fibrillation. In our review, we present the most recent clinical guidelines and trends for the approach to and management of this patient group.

Topics: Anticoagulants; Antifibrinolytic Agents; Aspirin; Atrial Fibrillation; Factor VIIa; Heparin; Humans; Intracranial Hemorrhages; Plasma; Recombinant Proteins; Stroke; Thrombolytic Therapy; Vitamin K; Warfarin

To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation.. We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=-0.59; P=0.002) and thromboembolic rates (r=-0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=-0.78; P=0.006 and thromboembolic rate, r=-0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=-0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events).. In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Clinical Trials as Topic; Hemorrhage; Humans; Prognosis; Time Factors; Vitamin K

The focus of this review is the evolving field of antithrombotic drug therapy for stroke prevention in patients with atrial fibrillation (AF). The current standard of therapy includes warfarin, acenocoumarol and phenprocoumon which have proven efficacy by reducing stroke by 68% against placebo. However, a narrow therapeutic index, wide variation in metabolism, and numerous food and drug interactions have limited their clinical application to only 50% of the indicated population. Newer agents such as direct thrombin inhibitors, factor Xa inhibitors, factor IX inhibitors, tissue factor inhibitors and a novel vitamin K antagonist are being developed to overcome the limitations of current agents. The direct thrombin inhibitor dabigatran is farthest along in development. Further clinical trial testing, and eventual incorporation into clinical practice will depend on safety, efficacy and cost. Development of a novel vitamin K antagonist with better INR control will challenge the newer mechanistic agents in their quest to replace the existing vitamin K antagonists. Till then, the large unfilled gap to replace conventional agents remains open. This review will assess all these agents, and compare their mechanism of action, stage of development and pharmacologic profile.

Topics: Anticoagulants; Atrial Fibrillation; Biological Availability; Factor IX; Factor Xa Inhibitors; Half-Life; Humans; Stroke; Thrombin; Vitamin K

Anticoagulation therapy in patients with atrial fibrillation is important. This review consists of three parts: chronic anticoagulation, anticoagulation for cardioversion, and a brief comment on anticoagulation around the time of left atrial radiofrequency ablation. The risk stratification scheme of the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines for chronic anticoagulation is briefly reviewed. Although there are several other similar schemes, they are not identical. The key point is the balance between benefit and risk. Some emerging controversies are outlined. Two specific questions explored are: is well-controlled hypertension a risk factor, and does paroxysmal atrial fibrillation confer the same risk as continuous atrial fibrillation? Differences in the risk of bleeding while taking a vitamin K antagonist noted in recent compared with older data are discussed. Risk of bleeding in the elderly and combined antithrombotic therapy with a vitamin K antagonist and an antiplatelet agent in high-risk patients are briefly discussed. Recent failures of studies attempting to find a suitable alternative to vitamin K antagonists are outlined. The treatment guidelines for anticoagulation for cardioversion are briefly reviewed. The risk of thromboembolism according to international normalized ratio and use of low-molecular-weight heparin as an alternative to warfarin are discussed. Anticoagulation before and after left atrial radiofrequency ablation is empirical, and long-term anticoagulation seems advisable for high risk patients at the present time. The two most pressing needs for further investigation are (1) clarification, simplification, and consolidated of risk stratification schemes and treatment recommendations and (2) discovery of alternatives to warfarin.

Topics: Age Factors; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Electric Countershock; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Tachycardia, Paroxysmal; Thromboembolism; Vitamin K

The expanding demand for long-term antithrombotic therapy and the major limitations of the vitamin-K antagonists, namely their narrow therapeutic range, numerous drug interactions and need for laboratory monitoring, have stimulated the development of new antithrombotic agents. Direct thrombin inhibitors and factor Xa inhibitors are the new classes of orally available anticoagulants that are most advanced in development. Large clinical trials evaluate several compounds both in the primary and secondary prevention of venous thromboembolism and in the prevention of cardioembolism in patients with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation Factors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Thrombosis; Vitamin K

Atrial fibrillation (AF) is associated with a 6 fold increased risk for ischemic stroke. Observational studies suggest that one in four to five strokes is due to AF. Depending on the risk profile of an individual patient, the yearly risk for ischemic stroke is between 2% and 14%. AF is accompanied by an increased propensity for atrial clot formation due to a combination of decreased atrial blood flow, increased activity of the platelet/plasmatic coagulation system and prothrombotic changes at the atrial endocardium. This review summarizes the current guidelines for thromboembolic prevention in patients with AF. In many cases, continuous oral anticoagulation therapy (OAT) with vitamin K antagonists (VitKAs) is indicated if AF is accompanied by more than one additional risk factor for thromboembolic complications. However, therapeutic range of VitKAs (Phenprocoumon, Warfarin, and others), the most commonly used oral anticoagulants, is narrow and their use requires regular anticoagulation monitoring. Possibly due to these limitations, about one third of eligible patients are not treated with VitKAs. Furthermore, in many treated patients OAT is not well controlled. Thus, in clinical practice anticoagulation therapy in AF is suboptimal. Therefore, new and more convenient pharmacologic approaches to prevent thromboembolism with i.e. direct thrombin inhibitors (DTI), synthetic polysaccharides (factor Xa Inhibitors), and others are discussed, and their possible future role in the treatment of AF is evaluated.

Topics: Anticoagulants; Atrial Fibrillation; Factor X; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stroke; Thrombin; Thromboembolism; Vitamin K

Given the projected rising prevalence of atrial fibrillation in the near future, an increasing number of older patients will have to be treated in order to prevent stroke and systemic embolism. This article summarizes recent developments in antithrombotic treatment and risk stratification for patients with atrial fibrillation and intends to abate the still prevailing reluctance towards anticoagulation in elderly patients.

Topics: Acute Disease; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Infarction; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Risk Factors; Secondary Prevention; Vitamin K

The frequency of pathologies requiring anticoagulant treatment (thromboembolic disease, atrial fibrillation) is particularly high in people above 75. The risk of haemorrhagic complications is also highest in this population of patients.Therefore, the assessment of the risk/benefit ratio of an anticoagulant treatment may overestimate the haemorrhagic risk and lead to the under-using of anticoagulant treatment in such pathologies as atrial fibrillation. CURRENT KNOWLEDGE AND KEY-POINTS: However, the use of "classical" anticoagulant treatments such as non-fractionated heparin, low-molecular-weight heparin, and above all, antivitamin K requires special precautions. Several hemorrhagic risk factors are well known and should be spotted out. Finally, the risk/benefit ratio of an anticoagulant treatment in the elderly patients must rely on a comprehensive geriatric assessment.. In the era of "new anticoagulant treatments", and particularly of per-os antithrombin, it may seem anachronous to issue a statement over the use of "classical anticoagulant treatments", but in the present state of knowledge, the evaluation of these new molecules is not sufficient in the elderly population of patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Geriatric Assessment; Heparin; Heparin, Low-Molecular-Weight; Humans; Risk Assessment; Risk Factors; Thromboembolism; Treatment Outcome; Vitamin K

Provided that account is taken of the criteria discussed in the present article, there is no doubt about the therapeutic benefits of effective anticoagulation in patients with chronic atrial fibrillation. Indeed, it is to be expected that the previously valid therapeutic guidelines are more likely to be expanded to reduce feared thromboembolic complications to a minimum, as is exemplified by the recommendation that the application of anticoagulation treatment with vitamin K antagonists should be continued over the longer term, that is, after the restoration of sinus rhythm. Furthermore, there is hope that effective drugs with a calculable (level of) safety and simplicity of administration may soon become available.

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Echocardiography; Electric Countershock; Fibrinolytic Agents; Heart Diseases; Humans; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Factors; Stroke; Thromboembolism; Thrombosis; Time Factors; Vitamin K

The management of patients who require temporary interruption of vitamin K antagonists is a common clinical problem, affecting an estimated 400 000 patients per year in Europe and North America. Managing such patients is challenging because of the lack of randomized trials assessing different perioperative anticoagulation management strategies and inconsistent recommendations from consensus groups. Recent non-randomized trials have helped to estimate the risks for arterial thromboembolism and bleeding with bridging anticoagulation involving low-molecular-weight heparin. The objectives of this review are to describe bridging anticoagulation and how it may be used with a short-acting heparin, such as unfractionated heparin or low-molecular-weight heparin, to discuss preoperative patient management, focusing on risk stratification for thromboembolic events and interruption of vitamin K antagonist therapy, and to discuss postoperative patient management, focusing on surgery-related bleeding risk and the resumption of bridging anticoagulation and vitamin K antagonist therapy.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Intraoperative Care; Platelet Aggregation Inhibitors; Postoperative Care; Practice Guidelines as Topic; Preoperative Care; Risk Assessment; Risk Factors; Surgical Procedures, Operative; Thromboembolism; Time Factors; Vitamin K

Stroke outcomes in patients with atrial fibrillation (AF) tend to be worse than those in patients without AF. The objective of this study was to evaluate whether the cost benefits of anticoagulation for stroke prevention in AF may currently be underestimated by existing economic models that do not distinguish between different stroke outcomes.. A literature review was conducted in 3 areas: (1) studies comparing stroke outcomes in AF and non-AF patients; (2) studies providing long-term cost of stroke estimates; and (3) studies modeling the cost-effectiveness of anticoagulation with a vitamin K antagonist (eg, warfarin) in AF patients.. There is considerable evidence that stroke in AF patients has a worse outcome than in patients without AF, including higher mortality, severity, and recurrence rates, and greater functional impairment and dependency. Estimates of the long-term cost of stroke of different severities were between US 24,991 dollars for a mild stroke over 5 years and US 142,251 dollars for a major ischemic stroke over a lifetime (2004 prices). The cost of a severe ischemic stroke may typically be 3-times that of mild stroke. However, cost-effectiveness models for anticoagulation in patients with AF have used average (not AF-specific) cost-of-stroke data, and most have used stroke severity distributions derived from clinical trials, which may differ from those in clinical practice.. Existing economic models underestimate the cost benefits of anticoagulation for stroke prevention because they do not adjust for poorer outcomes associated with cardioembolic strokes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Ischemia; MEDLINE; Middle Aged; Models, Theoretical; Multivariate Analysis; Quality-Adjusted Life Years; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Chronic, nonvalvular atrial fibrillation occurs more frequently with increasing age, together with an increasing risk for ischemic stroke. Guidelines recommend oral anticoagulation with a vitamin K antagonist for patients >65 years without risk factors and patients <65 years with risk factors for cardiac diseases. Advancing age also increases the risk for bleeding complications under oral anticoagulants; thus, only a part of these patients receives anticoagulant therapy. The risk of falls in elderly patients is of advancing relevance for this therapeutic decision. Oral direct thrombin inhibitors like ximelagatran may be an alternative choice for therapy. Ischemic strokes and systemic embolism in the same frequency with 2x36 mg ximelagatran over 18 months (91/3664 patients: 1.6%/year, for study Sportif III and Sportif V) compared with warfarin (93/3665 patients: 1.6%/year for study Sportif III and Sportif V). All bleeding complications occurred less frequently under therapy with ximelagatran. This could be of importance for elderly patients with risk factors for bleeding or risk of falling.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Cerebral Infarction; Clinical Trials as Topic; Hemorrhage; Humans; Risk Factors; Thromboembolism; Vitamin K; Warfarin

Congenital cardiopathy is common in children with thromboembolic disease. There are no objective clinical data for medium and long term treatment. Vitamin K antagonists could be envisaged for this. Children with a mechanical valve should be anticoagulated. This has been validated in adults, there has been no study in children which contradicts this, and the serious nature of thromboembolic complications in this group is significant. In atrial fibrillation, the most frequent indication for oral anticoagulants is after a Fontan procedure, because of the thromboembolic risk factors. Anticoagulation following Fontan or similar procedures relies on the thrombotic factors and their temporal distribution, being more pronounced in the first postoperative year; anticoagulants should be given over this period. In Eisenmenger's syndrome haemorrhage is common: these patients are not anticoagulated unless there is an indication such as recent pulmonary embolus. During interventional catheterisation thromboembolic accidents are rare, occurring early, and more commonly with certain prostheses. In adults with an intra-atrial prosthesis oral anticoagulants are used for three months, and then replaced by antiplatelet drugs. In congenital cardiopathy the stent is often pulmonary or aortic, and the incidence of thromboembolic accident is therefore very low. For a venous channel or in the context of a Fontan procedure, oral anticoagulants are justified for between three and six months. It is to be hoped that prospective studies, of which some are in progress, will provide further guidance for these indications.

Topics: 4-Hydroxycoumarins; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Child; Eisenmenger Complex; Fontan Procedure; Heart Defects, Congenital; Hemorrhage; Humans; Indenes; Risk Factors; Stents; Thromboembolism; Vitamin K

Nonvalvular atrial fibrillation (AF) is an independent risk factor for stroke that becomes increasingly prevalent as populations age. More than half a dozen clinical trials have demonstrated that anticoagulation with the vitamin K antagonist warfarin is the most effective therapy for stroke prophylaxis in AF. The narrow therapeutic index of warfarin requires that the intensity of anticoagulation be maintained within the international normalized ratio (INR) range of 2.0 to 3.0 to optimize efficacy while minimizing bleeding risk. The pharmacokinetics of warfarin are subject to variability due to interactions with multiple drugs and foods, making maintenance of the INR within this range difficult to achieve in clinical practice without close coagulation monitoring and frequent dose adjustments. Current guidelines recommend oral anticoagulation for high-risk individuals with AF but these inherent limitations lead to substantial underprescribing, particularly in elderly patients at greatest risk. This has stimulated the development of new agents with improved benefit-risk profiles, such as ximelagatran, the first of the oral direct thrombin inhibitors, which has a wider therapeutic margin and low potential for drug interactions, allowing fixed dosing without anticoagulation monitoring. Ximelagatran has been evaluated for stroke prevention in AF in the Stroke Prevention using an Oral Direct Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) program, the largest clinical trials of antithrombotic therapy for stroke prevention in AF to date. The phase III trials of ximelagatran in AF, SPORTIF III and V, found a fixed oral dose of ximelagatran (36 mg twice daily) comparable to dose-adjusted warfarin (INR 2.0 to 3.0) in preventing stroke and systemic thromboembolic complications among high-risk patients with AF. Results from the population of over 7000 patients in SPORTIF III and V demonstrate noninferiority of ximelagatran compared with warfarin. Data from SPORTIF III show an absolute reduction in stroke and systemic embolic events with ximelagatran compared with warfarin of 1.6% per year versus 2.3% per year, respectively ( P = 0.10). SPORTIF V further supports noninferiority between the two agents with an absolute risk reduction of 0.45%, well within the predefined noninferiority margin (95% confidence interval -0.13, 1.03; P = 0.13). Although event rates for major bleeding did not differ significantly with ximelagatran versus warfarin in either study, combined

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Hemorrhage; Humans; Risk Assessment; Stroke; Thrombin; Vitamin K; Warfarin

A 75-year-old man was admitted to our clinic with the complaints of palpitation, fever, severe dyspnea, dizziness and bloody sputum associated with coughing. Chest radiographs revealed that the lungs were bilaterally infiltrated. A high resolution computed tomographic study of the thorax disclosed diffuse alveolar hemorrhage, of which presence was proved by histopathological study of bronchoalveolar lavage material. The hemorrhage occured at 8th day of 5 mg daily warfarin therapy, which was given for frequent atrial fibrillation attacks was controlled by fresh frozen plasma and vitamin K. Alveolar hemorrhage is difficult to diagnose and has high mortality if the treatment was not started as soon as possible. This is the first report of alveolar hemorrhage caused by 5 mg daily warfarin therapy. We propose that the patient's age, nutritional status, used drugs should be taken into consideration for true management of patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Hemorrhage; Humans; International Normalized Ratio; Lung Diseases; Male; Pulmonary Alveoli; Tomography, X-Ray Computed; Vitamin K; Warfarin

As one of the most powerful independent risk factors for ischemic stroke and the most clinically relevant arrhythmia, atrial fibrillation (AF) poses a serious clinical and public health threat as the global population ages. AF increases the risk of ischemic stroke 4- to 5-fold although this statistic varies with age of the patient. Indeed, the prevalence rises to 1 in 25 people aged > or =60 years and 1 in 10 people aged > or =80 years. More than 2.3 million Americans have diagnosed AF, and that number is expected to increase dramatically over the coming decades. Ischemic stroke causes the most major disability and remains the third leading cause of death in the United States. Therapeutic strategies and optimal risk stratification offer the best hope for decreasing the burden of AF-related thromboembolism. This article focuses on the randomized trial evidence for the efficacy and safety of oral vitamin K antagonists (eg, warfarin) for stroke prevention in AF. In particular, this article explores how well these findings translate into clinical practice, especially among patients with AF treated outside of clinical trials. Discussion centers on using evidence-based data to guide treatment for patients who are at increased risk for stroke. Such strategies would enhance the net benefit of oral anticoagulation. Concluding points provide information on improving risk stratification for stroke in patients with AF.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Risk Factors; Stroke; United States; Vitamin K

This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range, 2.0 to 3.0): In patients with persistent or paroxysmal AF (PAF) [intermittent AF] at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus), we recommend anticoagulation with an oral VKA, such as warfarin (Grade 1A). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, we recommend antithrombotic therapy with either an oral VKA or aspirin, 325 mg/d, in this group of patients who are at intermediate risk of stroke (Grade 1A). In patients with persistent AF or PAF < 65 years old and with no other risk factors, we recommend aspirin, 325 mg/d (Grade 1B). For patients with AF and mitral stenosis, we recommend anticoagulation with an oral VKA (Grade 1C+). For patients with AF and prosthetic heart valves, we recommend anticoagulation with an oral VKA (Grade 1C+); the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. For patients with AF of > or = 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA for 3 weeks before and for at least 4 weeks after successful cardioversion (Grade 1C+). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacologic or electrical cardioversion, an alternative strategy is anticoagulation and screening multiplane transesophageal echocardiography (Grade 1B). If no thrombus is seen and cardioversion is successful, we recommend anticoagulation for at least 4 weeks (Grade 1B). For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulat

Topics: Aged; Atrial Fibrillation; Atrial Flutter; Electric Countershock; Evidence-Based Medicine; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Vitamin K

The news concerning anticoagulant therapy is very rich. It was also keenly awaited in view of the real imperfection of antivitamin K drugs on which the present strategy of prevention of thromboembolic risk related to atrial fibrillation is based. The new anticoagulants have differing targets identified from the physiological mechanism of coagulation and the physiopathology of thrombosis.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Thrombosis; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Diabetes Complications; Drug Interactions; Humans; International Normalized Ratio; Male; Practice Guidelines as Topic; Stroke; Thromboembolism; Vitamin K; Warfarin

When a patient who has been taking warfarin long-term needs to undergo surgery, how to manage his or her anticoagulation is controversial. We believe most patients should stop taking warfarin 5 days before elective surgery, and most do not need to receive heparin in the perioperative period as a bridge to surgery.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Protocols; Comorbidity; Endoscopy, Gastrointestinal; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Perioperative Care; Risk Assessment; Surgical Procedures, Operative; Thromboembolism; Vitamin K; Warfarin

Anticoagulants are widely used for the prevention and treatment of venous and arterial thrombosis. Current treatment strategies often employ a combination of parenteral and oral agents because the only available orally active anticoagulants, vitamin K antagonists, have a delayed onset of action. Furthermore, vitamin K antagonists have a narrow therapeutic window that necessitates careful anticoagulation monitoring, and dosing is problematic because of multiple food and drug interactions. These limitations highlight the need for oral anticoagulants that produce a more predictable anticoagulant response than vitamin K antagonists, thereby obviating the need for laboratory monitoring. Ximelagatran has the potential to meet this need. A prodrug of melagatran, an agent that targets thrombin, ximelagatran exhibits many of the characteristics of an ideal anticoagulant. This article (1). reviews the limitations of vitamin K antagonists, (2). lists the characteristics of an ideal anticoagulant, (3). rationalizes thrombin as a target for new anticoagulants, (4). reviews the preclinical and clinical data with ximelagatran, and (5). provides clinical perspective as to the future of ximelagatran and other orally active anticoagulants currently under development.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Blood Coagulation; Drug Monitoring; Glycine; Humans; International Normalized Ratio; Postoperative Complications; Prodrugs; Stroke; Thrombin; Thrombosis; Venous Thrombosis; Vitamin K

Topics: Aged; Aspirin; Atrial Appendage; Atrial Fibrillation; Humans; Intracranial Embolism; Prevalence; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Disease Progression; Electric Countershock; Electrophysiologic Techniques, Cardiac; Humans; Risk Factors; Secondary Prevention; Thromboembolism; Time Factors; Vitamin K

Anticoagulant therapy has recently undergone a surge in popularity with the confirmation of its importance in preventing cerebral thromboembolism from atrial fibrillation. Unfortunately oral anticoagulants have an extremely narrow therapeutic index and many physicians are reluctant to treat, particularly old patients, because of the fear of hemorrhagic complications and difficulty of management. The anticoagulant clinic, by improving therapeutic effectiveness and reducing complications, hospitalization and emergency room visits, appears to offer important qualitative and cost advantages over routine medical care. New strategies have been developed for managing care. One promising modality employs patients in their own care by performing their prothrombin time measurement by themselves at home. This model, similar to the way diabetics measure their own blood sugar, is possible as a result of a new class of point-of-care instrumentation for prothrombin testing. These portable monitors can measure a prothrombin time from a finger-stick sample of whole blood and provide a result within seconds. However rigorous studies are necessary to confirm the preliminary results of new management strategies to maximize the benefit-risk ratio of anticoagulant therapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Female; Hemorrhage; Hemostatics; Humans; Male; Monitoring, Physiologic; Multicenter Studies as Topic; Pregnancy; Prothrombin Time; Randomized Controlled Trials as Topic; Self Care; Thromboembolism; Vitamin K; Warfarin

To review the risk and pathogenesis of stroke associated with nonvalvular atrial fibrillation (AF) and the efficacies and risks of stroke prevention strategies.. About 16% of ischemic strokes are associated with AF; AF is an independent risk factor for stroke.. Review of the literature, focusing on 13 randomized trials of antithrombotic therapy.. The overall risk of stroke in AF patients averages about 5%/y, but with wide variation depending on the presence of coexistent thromboembolic risk factors. AF patients with low (about 1% per year), moderate (about 3% per year), and high (about 6% per year) stroke risks have been identified, but the generalizability of risk stratification schemes to clinical practice has not been fully assessed. AF patients with prior stroke or transient ischemic attack, even if remote, are at highest risk (about 12% per year). Adjusted-dose warfarin (target International Normalized Ratio [INR] 2-3) is highly efficacious for preventing stroke in AF patients (about 70% risk reduction) and is safe for selected patients, if carefully monitored. Aspirin has a modest effect on reducing stroke (about 20% risk reduction). The numbers of AF patients that would need to be treated with warfarin instead of aspirin for 1 year to prevent one ischemic stroke are about 200, 70, and 20 for those with low, moderate and high risk, respectively.. Many patients with nonvalvular AF have substantial rates of ischemic stroke. Stratification of stroke risk identifies AF patients who benefit most and least from lifelong anticoagulation. Warfarin is recommended for high-risk AF patients who can safely receive it. Aspirin may be indicated for those with a low stroke risk and for those who cannot receive warfarin. For AF patients considered to have a moderate risk of stroke, individual bleeding risk during anticoagulation and patient preference should particularly influence the choice of antithrombotic prophylaxis.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Female; Humans; Male; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Vitamin K; Warfarin

In comparison with the incidence of cerebrovascular accident in the general population, atrial fibrillation increases the risk by a factor of five. Although age is without doubt the main risk factor for cerebrovascular accidents in patients with permanent of paroxysmal non-valvular atrial fibrillation, other independent risk factors have been identified: a previous history of hypertension, cerebrovascular accident, heart failure or diabetes. These factors enable identification of a population at risk in which oral anticoagulation may be recommended with an excellent efficacy/risk ratio. Six large scale randomised controlled multicenter trials of primary prevention have been published with a total of over 2,800 patients with non-valvular atrial fibrillation. The combined results of these trials show that treatment with vitamin K antagonist (INR 2-3) leads to a significant reduction in the risk of an ischaemic cerebrovascular accident of 64% (95% CI [51-74]; p < 0.001) and in the risk of death from all causes of 28% (95% CI [12-47]; p = 0.038) with a slight increase in the risk of cerebral haemorrhage (+ 2.7% NS). Although the benefits of aspirin therapy are not as impressive (reduction of the risk of an ischaemic cerebrovascular accident of 22%; 95% CI [0-39]; p = 0.053), this alternative may be proposed in patients under 75 years of age without the previously mentioned risk factors. The value of combined aspirin-oral anticoagulant therapy, especially in high risk patients, has not yet been established and is under evaluation.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Middle Aged; Platelet Aggregation Inhibitors; Primary Prevention; Risk Factors; Treatment Outcome; Vitamin K; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Echocardiography; Europe; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Placebos; Risk Factors; Thromboembolism; Vitamin K

The various applications of anticoagulation in cardiology concern primary prevention, treatment of angina and infarction, revascularization either by angioplasty or by bypass grafts, treatment after artificial valve replacement, treatment of atrial fibrillation and, finally, as a precaution in the case of impaired ventricular function. Several methods of anticoagulation can be used in each of these indications: thrombin antagonists, vitamin K antagonists, antiaggregants and thrombolytics, although this last group is not discussed in this article.

Topics: 4-Hydroxycoumarins; Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Coumarins; Cyclooxygenase Inhibitors; Heparin; Humans; Indenes; Myocardial Infarction; Postoperative Care; Vitamin K

Whether or not atrial fibrillation is alone, if not idiopathic, is difficult to determine. The risk of embolization in lone atrial fibrillation is distinctly higher in healthy subjects over 60 years of age when the left atrium is dilated. In chronic atrial fibrillation this risk is higher than in paroxysmal fibrillation, especially within the year following the onset of the arrhythmia. In most patients anticoagulant therapy is effective in the primary or secondary prevention of embolic accidents. In subjects older than 75 aspirin given in daily doses of 325 mg seems to give similar results. The risk of antithrombosis therapy must not be underevaluated. The alternative is to maintain or restore the sinus rhythm, even at an advanced age, if the arrhythmia is recent and the left atrium is moderately dilated.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Amiodarone; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Humans; Indenes; Intracranial Embolism and Thrombosis; Male; Middle Aged; Recurrence; Risk Factors; Vitamin K; Warfarin

Systemic embolism secondary to chronic atrial fibrillation usually affect the cerebral circulation. The risk of a cerebrovascular accident in patients with chronic atrial fibrillation, irrespective of the aetiology, is 1.8 to 7.5 times that of the general population. The embolic risk is 18 times greater in patients with atrial fibrillation related to the rheumatic heart disease. The risk of patients under 60 years of age with idiopathic atrial fibrillation does not seem to be different to that of the general population. The risk of early recurrence of embolism in the first 30 days ranges from 8 to 15%. The risk of late recurrence varies but seems to be higher than that of the general population. The prognosis of embolic cerebrovascular accidents is poor with a 20% mortality rate. The benefits of preventive therapy of embolism with oral anticoagulants have been clearly established in rheumatic atrial fibrillation and in other indications. In non-valvular atrial fibrillation the benefits have to be compared with the risks of treatment. The incidence of hemorrhage due to anticoagulant therapy is between 3 and 5% per year per patient (about 1% of severe haemorrhage). Three randomised studies of primary prevention have shown a significant reduction of the embolic risk in non-valvular atrial fibrillation treated by warfarin compared to patients on placebo. Only one study has shown a significant reduction of the embolic risk in patients under 75 years of age with non-valvular atrial fibrillation treated with 325 mg/day of aspirin. However, anticoagulant therapy does not seem necessary in carefully selected patients under 60 years of age with idiopathic atrial fibrillation (less than 5% of all patients).

Topics: Aspirin; Atrial Fibrillation; Chronic Disease; Heart Valve Diseases; Humans; Primary Prevention; Prognosis; Recurrence; Risk; Thromboembolism; Vitamin K

Topics: Acute Disease; Anticoagulants; Atrial Fibrillation; Cell Transformation, Neoplastic; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Embolization, Therapeutic; Female; Hemorrhage; Heparin; Humans; Mitral Valve; Postoperative Complications; Pregnancy; Pulmonary Embolism; Thrombocytopenia; Thromboembolism; Thrombophlebitis; Vitamin K; Warfarin

Anticoagulation could not be currently stopped even after successful thoracoscopic ablation of atrial fibrillation for at least 2 months. The aim of this study is to compare the safety and efficacy outcomes between a new oral anticoagulant and warfarin after thoracoscopic ablation. This trial was a single-center, prospective, randomized controlled study comparing edoxaban and warfarin in patients undergoing thoracoscopic ablation of atrial fibrillation. This study enrolled 60 patients randomly assigned into 2 groups. The primary endpoint was efficacy outcomes, including stroke and systemic thromboembolic events. The secondary endpoint was safety outcomes including major bleeding and pericarditis. The patients were evaluated at discharge, 2 weeks, 3 months, and 6 months postoperatively. No stroke and thromboembolic events were noted in both treatment groups during the follow-up period. During the 6 months follow-up period, 4 (13%) of 30 patients in the edoxaban group experienced minor bleeding events, whereas none were noted in the warfarin group. Five anticoagulation-related events (bleeding, and prolongation of international normalized ratio), including pericarditis, were noted in both the edoxaban and warfarin groups. No statistically significant difference existed between the 2 groups. In conclusion, this study showed the comparable results of edoxaban to warfarin during the window period of post-thoracoscopic ablation of atrial fibrillation. Moreover, anticoagulation-related events were rather affected by patient factors and not by the anticoagulant type.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Pericarditis; Prospective Studies; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

ENVISAGE-TAVI AF (Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation; NCT02943785) was a prospective, randomized, open-label trial comparing non-vitamin K oral anticoagulant (NOAC) edoxaban with vitamin K antagonists (VKAs) in patients with atrial fibrillation after successful transcatheter aortic valve replacement (TAVR). The effect of edoxaban- or VKA-based therapy on patient-reported outcomes remains unknown, as most studies focus on efficacy and safety. Pre-TAVR patient-reported expectations and post-TAVR Treatment Satisfaction and Convenience with edoxaban or VKA treatment (at months 3 and 12) were analyzed using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q). This analysis included randomized and dosed patients with an evaluable PACT-Q1 assessment at baseline and ≥1 postbaseline assessment (PACT-Q2). Subanalyses included patients stratified by pre-TAVR anticoagulant (NOAC, VKA, no NOAC/VKA). Edoxaban- (n = 585) and VKA-treated (n = 522) patients had similar baseline characteristics and treatment expectations. Pre-TAVR anticoagulant use did not affect treatment expectations. After TAVR, edoxaban-treated patients had significantly higher Treatment Satisfaction and Convenience scores compared with VKA-treated patients at all time points (p <0.001 for all). Among edoxaban-treated patients, those who received VKAs pre-TAVR were significantly more satisfied with treatment than those who received NOACs (p <0.001) or no NOACs/VKAs (p = 0.003); however, there was no significant difference in the perception of convenience (p = 0.927 and p = 0.092, respectively). Conversely, among VKA-treated patients, the type of anticoagulant used pre-TAVR did not affect Treatment Satisfaction or Convenience scores post-TAVR. In conclusion, patients with atrial fibrillation who received edoxaban post-TAVR reported significantly higher Treatment Satisfaction and Convenience scores compared with those who received VKAs, resulting in a clinically meaningful difference between treatment groups.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Patient Satisfaction; Prospective Studies; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

We aimed to assess the prevalence of ischemic brain lesions detected by magnetic resonance imaging and their association with cognitive function 3 months after first-time ablation using continuous oral anticoagulation in patients with paroxysmal atrial fibrillation (AF).. We performed a prespecified analysis of the AXAFA-AFNET 5 trial (Anticoagulation Using the Direct Factor Xa Inhibitor Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy), which randomized 674 patients with AF 1:1 to uninterrupted apixaban or vitamin K antagonist therapy before first-time ablation. Brain magnetic resonance imaging using fluid-attenuated inversion recovery and high-resolution diffusion-weighted imaging was obtained within 3 to 48 hours after AF ablation in all eligible patients enrolled in 25 study centers in Europe and the United States. Patients underwent cognitive assessment 3 to 6 weeks before ablation and 3 months after ablation using the Montreal Cognitive Assessment (MoCA).. In 84 (26.1%) of 321 patients with analyzable magnetic resonance imaging, high-resolution diffusion-weighted imaging detected at least 1 acute brain lesion, including 44 (27.2%) patients treated with apixaban and 40 (24.8%) patients treated with vitamin K antagonist (. Chronic white matter damage as well as acute ischemic lesions detected by brain magnetic resonance imaging were found frequently after first-time ablation for paroxysmal AF using uninterrupted oral anticoagulation. Acute ischemic brain lesions detected by high-resolution diffusion-weighted imaging were not associated with cognitive function at 3 months after ablation. Lower MoCA scores before and after ablation were associated only with older age, highlighting the safety of AF ablation on uninterrupted oral anticoagulation.. URL: https://www.. gov; Unique identifier: NCT02227550.

Topics: Anticoagulants; Atrial Fibrillation; Brain; Catheter Ablation; Cognition; Humans; Magnetic Resonance Imaging; Treatment Outcome; Vitamin K

Managing antithrombotic therapy in patients with atrial fibrillation (AF) and an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is challenging and can be affected by prior oral anticoagulant (OAC) treatment. We examined the relationship between prior OAC use and outcomes in the AUGUSTUS trial.. This prespecified secondary analysis is from AUGUSTUS, an open-label, 2-by-2 factorial, RCT to evaluate the safety of apixaban versus vitamin K antagonist (VKA) and aspirin versus placebo in patients with AF and ACS and/or PCI. The primary endpoint, major or clinically relevant non-major bleeding and clinical outcomes were compared in patients receiving (n=2262) or not receiving (n=2352) an OAC prior to enrolment.. Patients with prior OAC use had more comorbidities, higher CHA. In AUGUSTUS, prior OAC use was associated with fewer ischaemic events but not more bleeding. In patients with AF and ACS and/or undergoing PCI, clinicians can be assured that the trial results can be applied to patients regardless of their prior OAC status.. NCT02415400.

Topics: Acute Coronary Syndrome; Aspirin; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemia; Male; Medication Therapy Management; Middle Aged; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Preoperative Period; Pyrazoles; Pyridones; Vitamin K

Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).. The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months.. In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Pulmonary Embolism; Rivaroxaban; Stroke; Vitamin K

Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT.. In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Stroke; Japan; Male; Prospective Studies; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited.. We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA. Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted.. Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Topics: Anticoagulants; Atrial Fibrillation; Echocardiography; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Rheumatic Heart Disease; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.. The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.. This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.. NCT04730037.. This paper was written per the study protocol V.4.0, dated 29 January 2021.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Hypertension, Pulmonary; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Single-Blind Method; Stroke; Venous Thromboembolism; Vitamin K; Warfarin

Current guidelines recommend anticoagulation with a vitamin K antagonist to treat left ventricular (LV) thrombus after myocardial infarction (MI). Data on the use of direct oral anticoagulants (DOACs) in this setting are limited. The aim of the study was to assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI.. We conducted a prospective, randomized, multicentre open-label clinical trial including patients with LV thrombus detected by 2D transthoracic echocardiography 1-14 days after acute MI. Thirty-five patients were enrolled in three medical centres; 17 patients were randomized to warfarin and 18 patients to apixaban. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Secondary outcomes were major bleeding, stroke or systemic embolism, re-hospitalization, and all-cause mortality. Mean LV thrombus size at enrolment was 18.5 mm × 12.3 mm in the warfarin group and 19.9 mm × 12.4 mm in the apixaban group (P = NS). Thirty-two patients completed 3 months follow-up. In the warfarin group, two patients withdrew, and in the apixaban group one patient died. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 patients in the apixaban group (P = NS and P = 0.026 for non-inferiority). Two patients had major bleeding in the warfarin group, while no major bleeding events were recorded in the apixaban group. There was one stroke in the warfarin group and one death in the apixaban group.. Our results suggest that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI with a 20% non-inferiority margin.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Myocardial Infarction; Prospective Studies; Pyrazoles; Pyridones; Stroke; Thrombosis; Vitamin K; Warfarin

This post hoc analysis of ELIMINATE-AF evaluated requirements of unfractionated heparin (UFH) and procedure-related bleeding in atrial fibrillation (AF) patients undergoing ablation with uninterrupted edoxaban or vitamin K antagonist (VKA) therapy.. Patients were randomized 2:1 to once-daily edoxaban 60 mg (or dose-reduced 30 mg) or dose-adjusted VKA (target international normalized ratio: 2.0-3.0). Uninterrupted anticoagulation was mandated for 21-28 days' pre-ablation and 90 days' post-ablation. During ablation, UFH administration targeted an activated clotting time (ACT) of 300-400 s. Periprocedural bleeding was differentiated between procedure-related (bleeding at puncture side, cardiac tamponade) and unrelated events. Of 614 randomized patients, 553 received study drug and underwent catheter ablation (edoxaban n = 375; VKA n = 178). The median (Q1-Q3) time from last dose to ablation procedure was 14.8 (13.3-16.5) vs. 16.5 (14.8-19.5) h (edoxaban vs. VKA group, respectively). Mean ACT (SD) ≥300 s was observed in 52% edoxaban- vs. 76% VKA-treated patients, despite a higher mean (SD) UFH dose in the edoxaban vs. VKA group [14 261 (6397) IU vs. 11 473 (4300) IU; exploratory P-value < 0.0001]. In the edoxaban group, 13 patients (3.5%) had procedure-related bleeds of whom 9 had received an UFH dose above the median (13 000 IU). In the VKA arm, 7 patients (3.9%) had procedure-related bleeds of whom 3 had received an UFH dose above the median (10 225 IU).. The rate of procedure-related major/clinically relevant non-major bleeding did not differ between the treatment arms despite higher doses of UFH used with edoxaban vs. VKA to achieve a target ACT during AF ablation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Heparin; Humans; Pyridines; Thiazoles; Treatment Outcome; Vitamin K

In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown.. In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding.. Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68;. In patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA.. Oral Anticoagulation in Hemodialysis, NCT03799822.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Mortality; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Vitamin K; Vitamin K 2

The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.. We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding.. A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11).. In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Topics: 4-Hydroxycoumarins; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Mortality; Phenindione; Postoperative Complications; Pyridines; Thiazoles; Thromboembolism; Transcatheter Aortic Valve Replacement; Vitamin K

A high number of vitamin K antagonist (VKA) users have a low proportion of time in therapeutic range (TTR) resulting in a high number of bleeding and thromboembolism events.. Can the quality of anticoagulation be improved by dispensing VKAs via multidose drug dispensing (MDD).. A randomized controlled trial in the Netherlands. Patients who used VKAs, ≥65 years of age with a TTR <65% were eligible for inclusion. All oral drugs were dispensed via MDD. In MDD systems, all oral chronic medication intended for one dosing moment is packed in plastic disposable pouches. Controls received VKAs by manual dispensing. The difference in TTR between the 6 months after- and 6 months before the index date. A mixed-effects model with the intervention, TTR before the index date, MDD system at baseline as covariates, and pharmacy as random effect. A per-protocol analysis was performed with all patients who completed the study as intended.. One hundred and seventy-nine patients were included. Mean age was 80.0 (SD 6.9) years. Mean TTR during the study was 79.2 ± 18.0% in the intervention group and 72.5 ± 20.1% in the control group. The intervention resulted in a 5.6% (95% CI: 0.1-11.1) increase in TTR compared to the control group. Per-protocol analysis resulted in an 8.3% (95% CI: 0.99-15.61) increase in TTR compared to the control group. No differences in reduction were observed between the intervention and control group.. The quality of anticoagulation can be improved with the use of MDD systems.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Netherlands; Pharmaceutical Preparations; Vitamin K; Vitamins

Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation.. Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000. Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm.. Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Atrial Fibrillation; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Prospective Studies; Renal Dialysis; Rivaroxaban; Stroke; Vascular Calcification; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Coronary Thrombosis; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyrazoles; Pyridones; Risk Factors; Stents; Time Factors; Treatment Outcome; Vitamin K

Direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) prevent thromboembolism in atrial fibrillation (AF). DOAC have a fixed dosing regimen and obviate INR monitoring. Therefore, DOAC presumably affect quality of life (QoL) less than VKA. However, some VKA users appreciate the monitoring. A high time in the therapeutic range (TTR) leads to a lower impact on QoL. We assessed the influence of switching from well-controlled VKA to a DOAC on QoL.. In the GAInN study, 241 patients with AF, a TTR ≥ 70%, and neither bleeding nor thrombosis while on VKA were randomised to switching to DOAC (n = 121) or continuing VKA (n = 120). Health-related (SF-36) and anticoagulation-related QoL (PACT-Q) was assessed at baseline and after six and twelve months of follow-up.. SF-36 development did not differ between groups. After one year, average PACT-Q Convenience improvement was 2.5 (0.3-4.7) higher on DOAC. DOAC users were 6percentage points (95%CI -4-16) more likely to improve >5 points on Convenience; 22 pp. (95%CI 1-43) in patients who scored <95/100 at baseline. The probability to meaningfully improve on PACT-Q Satisfaction was 12 pp. (95%CI 0-25) higher on DOAC. However, 5 (4.1%) and 4 (3.3%) DOAC users resumed VKA because of side-effects and patient preference. Switching from well-controlled VKA to DOAC for AF leads to a higher probability of improved PACT-Q convenience and satisfaction, but also to a higher risk of side-effects. Arguably only patients who are not satisfied with VKA should switch, because they have more to gain by switching.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Quality of Life; Vitamin K

Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need.. The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm. INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Topics: Adult; Aged; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Rheumatic Heart Disease; Rivaroxaban; Stroke; Vitamin K

Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut.. Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate ('one-way') deterministic sensitivity analysis.. We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Pragmatic Clinical Trials as Topic; Primary Health Care; Safety; Spain; Stroke; Treatment Outcome; Vitamin K; Warfarin

Although randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice.. To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice.. Patients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea's nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin.. Of the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54-0.71; 0.60, 0.53-0.69; and 0.71, 0.56-0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51-0.66 and 0.75, 0.60-0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69-1.04), showed a significantly lower MB risk than warfarin.. Among Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Vitamin K; Warfarin

Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring.. We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF).. Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks.. In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3-89.7), 85.2% (95% CI 81.5-88.2), and 87.8% (95% CI 83.4-91.1). Serious adverse events were similar across groups.. High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits.. This study is registered at ClinicalTrials.gov [NCT01884350].

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Medication Adherence; Pyrazoles; Pyridones; Risk Factors; Stroke; Vitamin K

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its prevalence increases with age. Few data are available about the clinical performance of direct oral anticoagulant (DOACs) in patients aged ≥ 80 years with AF. The aim of our propensity score matched cohort study was to compare the safety and efficacy of DOACs versus well-controlled VKA therapy among octogenarians with AF in real life setting. Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874), which includes all AF patients followed by the participating centers, through outpatient visits every 3 to 6 months. The database was queried for AF patients aged ≥ 80 years who received DOACs or VKAs treatment. The primary effectiveness endpoint was the occurrence of thromboembolic events (a composite of stroke, transient ischemic attack, systemic embolism); the primary safety endpoint was the occurrence of major bleeding; the secondary endpoint was all-cause mortality. The database query identified 774 AF patients aged ≥ 80 years treated with VKAs and 279 with DOACs. Propensity score (2:1) matching selected 252 DOAC and 504 VKA recipients. The mean follow-up was 31.07 ± 14.09 months. The incidence rate of thromboembolic events was 13.79 per 1000 person-years [14.80 in DOAC vs 13.34 in VKA group, Hazard Ratio 1.10; 95% confidence interval (CI) 0.49 to 2.45; P = 0.823]. The incidence rate of intracranial hemorrhage (ICH) was 8.06 per 1000 person-years (3.25 in DOAC vs 10.23 in VKA group, HR 0.33; 95% CI 0.07 to 1.45; P = 0.600). Through these incidence rates, we found a positive net clinical benefit (NCB) of DOACs over VKAs, equal to + 9.01. The incidence rate of all-cause mortality was 105.05 per 1000 person-years (74.67 in DOAC vs 118.67 in VKA group, Hazard Ratio 0.65; 95% CI 0.47 to 0.90; P = 0.010). The concomitant use of antiinflammatory drugs (HR 7.90; P < 0.001) were found to be independent predictor of major bleeding. Moreover, age (HR 1.17; P < 0.002) and chronic kidney disease (HR 0.34; P = 0.019) were found to be independently associated with thromboembolic events. In our study no significant difference in terms of both thromboembolic and major bleeding events, but a significant lower incidence of all-cause mortality, was detected in AF patients aged ≥ 80 years treated with DOACs vs VKAs.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Disease-Free Survival; Follow-Up Studies; Hemorrhage; Humans; Incidence; Propensity Score; Prospective Studies; Risk Factors; Survival Rate; Thromboembolism; Vitamin K

We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI).. ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed.. From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority).. In patients with atrial fibrillation who had PCI, the edoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events.. Daiichi Sankyo.

Topics: Acute Coronary Syndrome; Aged; Atrial Fibrillation; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Pyridines; Stents; Stroke; Thiazoles; Vitamin K

The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI.. Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y. An antithrombotic regimen consisting of apixaban and a P2Y. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Agents; Combined Modality Therapy; Disease Management; Drug Therapy, Combination; Elective Surgical Procedures; Female; Fibrinolytic Agents; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Purinergic P2Y Receptor Antagonists; Pyrazoles; Pyridones; Treatment Outcome; Vitamin K

Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy.. Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y. Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stents; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Clinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF). Frail elderly were under-represented in the landmark NOAC-trials, leaving a knowledge gap on the optimal anticoagulant management (VKA or NOAC) in this increasing population. The aim of the Frail-AF (FRAIL-AF) study is to assess whether switching from international normalised ratio (INR)-guided VKA-management to a NOAC-based treatment strategy compared with continuing VKA-management is safe in frail elderly patients with AF.. The FRAIL-AF study is a pragmatic, multicentre, open-label, randomised controlled clinical trial. Frail elderly (age ≥75 years plus a Groningen Frailty Indicator score ≥3) who receive VKA-treatment for AF in the absence of a mechanical heart valve or severe mitral valve stenosis will be randomised to switch to a NOAC-based treatment strategy or to continue INR-guided VKA-management. Patients with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m. The protocol was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, the Netherlands and by the Central Committee on Research Involving Human Subjects, the Netherlands. All patients are asked written informed consent. Results are expected in 2022 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences.. EudraCT: 2017-000393-11; The Netherlands Trial Registry: 6721 (FRAIL-AF study).

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Frail Elderly; Humans; Male; Middle Aged; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Among atrial fibrillation patients undergoing percutaneous coronary intervention enrolled in PIONEER AF-PCI (An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), it is unclear if the observed reduction in bleeding events with rivaroxaban regimens is consistent across a range of the international normalized ratio (INR) among subjects administrated Vitamin K antagonist (VKA)-triple therapy. This analysis compares the occurrence of clinically significant bleeding between rivaroxaban and VKA strategies, according to INR stability of subjects administrated VKA.. A total of 2124 atrial fibrillation patients undergoing percutaneous coronary intervention were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y. Among atrial fibrillation patients undergoing percutaneous coronary intervention, rivaroxaban-based therapy was superior to warfarin plus dual antiplatelet therapy in lowering bleeding outcomes regardless of the INR stability.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01830543.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Coronary Artery Disease; Factor Xa Inhibitors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Vitamin K; Warfarin

 Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved..  We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial..  A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding..  The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66% vs. ≥66%) resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0%, +1.1%) and +2.2% (0.9%, +3.5%), respectively. Patients with high SAMe-TT2-R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7%). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66%), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0% (-0.6%, +0.7%) for recurrence and +1.3% (-0.1%, +2.7%) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365)..  In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Double-Blind Method; Female; Hemorrhage; Humans; International Normalized Ratio; Linear Models; Male; Middle Aged; Recurrence; Research Design; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Vitamin K

Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear.. In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y. Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group.. In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Pyrazoles; Pyridones; Vitamin K

Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested.. The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62).. Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.

Topics: Aged; Atrial Fibrillation; Catheter Ablation; Cerebral Hemorrhage; Factor Xa Inhibitors; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Postoperative Hemorrhage; Pyridines; Stroke; Thiazoles; Vitamin K

We investigated the use of different antithrombotic therapies at baseline among patients with a history of atrial fibrillation (AF), type 2 diabetes, and established atherosclerotic cardiovascular disease (ASCVD) enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).. TECOS participants with a history of AF were stratified by CHA. Of the 14,671 TECOS participants, 1167 (8%) had a history of AF, of whom 51.6% were using vitamin K antagonists (VKA); 31.2% used VKA alone, 16.9% used aspirin plus VKA, 1.8% used clopidogrel plus VKA, and 1.7% used aspirin and clopidogrel plus VKA. Aspirin was used by 56.8%: 30.9% used aspirin alone and 7.3% aspirin plus clopidogrel. Clopidogrel alone was used by 2.9%, and 7.3% were not using any antithrombotic medication. Participants with a history of AF had a higher risk of cardiovascular events, including hospitalization for heart failure and all-cause mortality, than those without AF. White, older men with prior myocardial infarction, heart failure, peripheral artery disease, or prior stroke were more likely to develop new-onset AF than others without these characteristics.. Almost half of high-risk AF patients with diabetes and established ASCVD in TECOS were not treated with anticoagulation therapy despite clear guideline recommendations for such therapy, highlighting the challenge and potential for clinical improvements in managing these patients in clinical practice.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Sitagliptin Phosphate; Stroke; Time Factors; Treatment Outcome; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists (VKA) for atrial fibrillation (AF) patients. Some studies have proposed that well-managed warfarin therapy is still a valid alternative as efficacious as NOACs but the potential impact and absolute effect of NOACs in "real world" optimally management of VKA AF patients is unknown.. To estimate the potential absolute benefit in clinical outcome rates if the optimally anticoagulated "real-world" AF patients with acenocoumarol had been treated with NOACs.. We included 1361 patients stable on acenocoumarol with a time in therapeutic range of 100% for the previous 6months and 6.5years of follow-up. The estimation of clinical events avoided was calculated applying absolute risk reductions, relative risk reductions and hazard ratios from the pivotal clinical trials, relative to acenocoumarol.. Compared to acenocoumarol, the highest estimated event reduction for stroke was seen with dabigatran 150mg, with an estimated reduction of 0.53%/year. For major bleeding, the highest estimated reduction was seen with apixaban (0.88%/year). For mortality, the largest estimated reduction was with dabigatran 150mg (0.75%/year). In net clinical outcome, apixaban had the estimated highest reduction (1.23%/year). All NOACs showed significantly lower rates for intracranial haemorrhage.. In optimally acenocoumarol anticoagulated AF patients, estimated reductions in stroke, bleeding and net clinical outcomes with various NOACs are evident. NOACs would potentially show an improvement even among optimally VKA AF patients.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Mortality; Prospective Studies; Retrospective Studies; Treatment Outcome; Vitamin K

It is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested.. We compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA, international normalized ratio 2-3) in atrial fibrillation patients at risk of stroke a prospective, open, multi-centre study with blinded outcome assessment. Primary outcome was a composite of death, stroke, or bleeding (Bleeding Academic Research Consortium 2-5). A high-resolution brain magnetic resonance imaging (MRI) sub-study quantified acute brain lesions. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at baseline and at end of follow-up. Overall, 674 patients (median age 64 years, 33% female, 42% non-paroxysmal atrial fibrillation, 49 sites) were randomized; 633 received study drug and underwent ablation; 335 undertook MRI (25 sites, 323 analysable scans). The primary outcome was observed in 22/318 patients randomized to apixaban, and in 23/315 randomized to VKA {difference -0.38% [90% confidence interval (CI) -4.0%, 3.3%], non-inferiority P = 0.0002 at the pre-specified absolute margin of 0.075}, including 2 (0.3%) deaths, 2 (0.3%) strokes, and 24 (3.8%) ISTH major bleeds. Acute small brain lesions were found in a similar number of patients in each arm [apixaban 44/162 (27.2%); VKA 40/161 (24.8%); P = 0.64]. Cognitive function increased at the end of follow-up (median 1 MoCA unit; P = 0.005) without differences between study groups.. Continuous apixaban is safe and effective in patients undergoing atrial fibrillation ablation at risk of stroke with respect to bleeding, stroke, and cognitive function. Further research is needed to reduce ablation-related acute brain lesions.

Topics: Aged; Atrial Fibrillation; Brain; Catheter Ablation; Cognition; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Direct acting non-Vitamin K antagonist oral anticoagulants (NOAC) are characterized by a fixed dosing regimen. Despite the potential for relative underdosing due to large distribution volumes, dose adjustments for patients with high body mass index (BMI) are not recommended. Since efficacy and safety data in obese patients are scarce, we evaluated the impact of BMI on clinical outcomes in daily care patients treated with NOAC for stroke prevention in atrial fibrillation or venous thromboembolism. Using prospectively collected data from a non-interventional registry, cardiovascular (CV), major bleeding events (MB) and all-cause mortality were evaluated according to BMI classes. All outcome events were centrally adjudicated using standard scientific definitions. Between November 1st 2011 and December 31st 2016, 3432 patients were enrolled into the registry (61.3% rivaroxaban; 20% apixaban; 10.1% dabigatran, 8.6% edoxaban; mean follow-up 998.1 ± 542.9 days; median 1004 days). With increasing BMI (range 13.7-57.2 kg/m

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Body Mass Index; Dabigatran; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Obesity; Prospective Studies; Pyrazoles; Pyridines; Pyridones; Registries; Rivaroxaban; Thiazoles; Thromboembolism; Treatment Outcome; Vitamin K

The primary objective was to compare apixaban to heparin/vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and ≤48 h anticoagulation prior to randomization undergoing cardioversion.. One thousand five hundred patients were randomized. The apixaban dose of 5 mg b.i.d. was reduced to 2.5 mg b.i.d. in patients with two of the following: age ≥ 80 years, weight ≤ 60 kg, or serum creatinine ≥ 133 µmol/L. To expedite cardioversion, at the discretion of the investigator, imaging and/or a loading dose of 10 mg (down-titrated to 5 mg) was allowed. The endpoints for efficacy were stroke, systemic embolism (SE), and death. The endpoints for safety were major bleeding and clinically relevant non-major (CRNM) bleeding.. There were 1038 active and 300 spontaneous cardioversions; 162 patients were not cardioverted. Imaging was performed in 855 patients, and 342 received a loading dose of apixaban. Comparing apixaban to heparin/VKA in the full analysis set, there were 0/753 vs. 6/747 strokes [relative risk (RR) 0; 95% confidence interval (95% CI) 0-0.64; nominal P = 0.015], no SE, and 2 vs. 1 deaths (RR 1.98; 95% CI 0.19-54.00; nominal P > 0.999). In the safety population, there were 3/735 vs. 6/721 major (RR 0.49; 95% CI 0.10-2.07; nominal P = 0.338) and 11 vs. 13 CRNM bleeding events (RR 0.83; 95% CI 0.34-1.89; nominal P = 0.685). On imaging, 60/61 with thrombi continued randomized treatment; all (61) were without outcome events.. Rates of strokes, systemic emboli, deaths, and bleeds were low for both apixaban and heparin/VKA treated AF patients undergoing cardioversion.. NCT02100228.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Drug Administration Schedule; Echocardiography, Transesophageal; Electric Countershock; Embolism; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Stroke; Tomography, X-Ray Computed; Treatment Outcome; Vitamin K

Patients with atrial fibrillation (AF) are at an approximately 0.5% to 3% increased risk of thromboembolism during and immediately after catheter ablation. Treatment guidelines recommend periprocedural oral anticoagulation plus unfractionated heparin during ablation. Rivaroxaban and dabigatran are the only non-vitamin K oral anticoagulants for which there are randomized controlled trials assessing uninterrupted anticoagulation in patients undergoing catheter ablation of AF. Edoxaban, a direct factor Xa inhibitor, is noninferior vs warfarin for the prevention of stroke or systemic embolism with less major bleeding in patients with nonvalvular AF. The ELIMINATE-AF (Evaluation of Edoxaban Compared With VKA in Subjects Undergoing Catheter Ablation of Nonvalvular Atrial Fibrillation) trial is a multinational, multicenter, prospective, randomized, open-label, parallel-group, blinded-endpoint evaluation (PROBE) study to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for a dose reduction) vs vitamin K antagonists (VKA) in patients with nonvalvular AF undergoing catheter ablation (http://www.ClinicalTrials.gov: NCT02942576). A total of 560 patients are planned for randomization to edoxaban or VKA (2:1 ratio) to obtain 450 patients fully compliant with the protocol. Patients will complete 21 to 28 days of anticoagulation prior to the ablation and a 90-day post-ablation period. The primary efficacy endpoint is the composite of all-cause death, stroke, and major bleeding. The primary safety endpoint is major bleeding. A magnetic resonance imaging substudy will assess the incidence of silent cerebral lesions post-ablation. ELIMINATE-AF will define the efficacy and safety of edoxaban for uninterrupted oral anticoagulation during catheter ablation of AF.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Catheter Ablation; Clinical Protocols; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Magnetic Resonance Imaging; Male; Prospective Studies; Pyridines; Research Design; Risk Factors; Stroke; Thiazoles; Time Factors; Treatment Outcome; Vitamin K; Warfarin

The tradeoff in safety versus efficacy in substituting a non-vitamin K antagonist oral anticoagulant for a vitamin K antagonist (VKA) in the stented atrial fibrillation patient has not been quantitatively evaluated.. Based on summary data from the PIONEER AF-PCI and RE-DUAL PCI trials, 4 antithrombotic regimens were compared with VKA-based triple therapy: (1) rivaroxaban (riva) 15 mg daily + P2Y. All 4 non-vitamin K antagonist oral anticoagulant regimens were superior in bleeding and noninferior in efficacy compared with triple therapy with VKA. Riva 15 mg daily and 2.5 mg twice daily were associated with bivariate combined risk reductions of 5.6% (2.3%-8.8%) and 5.5% (2.1%-8.7%), respectively, and dabi 110 mg twice daily and 150 mg twice daily reduced the bivariate risk by 3.8% (0.5%-7.0%) and 6.3% (2.4%-9.8%), respectively.. A bivariate analysis that simultaneously characterizes both risk and benefit demonstrates that riva- and dabi-based regimens were both favorable over VKA plus dual antiplatelet therapy among patients with atrial fibrillation undergoing PCI.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Care; Stroke; Time Factors; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Component Transfusion; Disease Management; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hemorrhage; Hemostatic Techniques; Humans; Incidence; Male; Prognosis; Registries; Stroke; Thromboembolism; Time Factors; United States; Vitamin K; Warfarin

Several non-vitamin K antagonist oral anticoagulant (NOAC) alternatives to warfarin are available for stroke prevention in atrial fibrillation (AF). We aimed to describe the factors associated with selection of NOACs versus warfarin in patients with new onset AF.. The ORBIT-AF II study is a national, US, prospective, observational, cohort study of anticoagulation treatment in patients with AF receiving NOACs or warfarin in the United States from 2013 to 2016. We measured factors associated with oral anticoagulant selection in 4,670 patients recently diagnosed with AF.. At baseline, 1,169 (25%) patients were started on warfarin and 3,501 (75%) on NOACs: of these latter, 259 (6%) were started on dabigatran, 1858 (40%) on rivaroxaban, and 1384 (30%) on apixaban. Those receiving NOACs were slightly younger patients (median age 71 vs 72, P<.0001); were less likely to have prior stroke (5.3% vs 8.6%; P<.0001) or prior bleeding (2.7% vs 4.4%; P=.005); had better kidney function (mean estimated glomerular filtration rate 91 mL/min vs 80 mL/min, P<.0001); and had fewer patients at high stroke risk (CHA. In contemporary clinical practice, up to three-fourths of patients with new-onset AF are now initially treated with a NOAC for stroke prevention. Those selected for NOAC treatment had lower stroke and bleeding risk profiles, were more likely treated by cardiologists, and had higher socioeconomic status.. clinicaltrials.gov Identifier: NCT01701817.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Registries; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K; Warfarin

Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation (AF). Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients. Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not known.. Stroke risk is higher in pacemaker patients with AHRE than in those without, but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF. Furthermore, only a minority of patients with AHRE will develop AF, many strokes occur without a temporal relation to AHRE, and AHRE can reflect other arrhythmias than AF or artifacts. An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed.. The Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence-based indications. The primary safety outcome will be major bleeding. NOAH-AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF, aged ≥65 years with at least 1 other stroke risk factor, to oral anticoagulation therapy (edoxaban) or no anticoagulation. All patients will be followed until the end of this investigator-driven, prospective, parallel-group, randomized, event-driven, double-blind, multicenter phase IIIb trial. Patients will be censored when they develop AF and offered open-label anticoagulation. The sponsor is the Atrial Fibrillation NETwork (AFNET). The trial is supported by the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research), and Daiichi Sankyo Europe.. NOAH-AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices.

Topics: Administration, Oral; Aged; Aspirin; Atrial Fibrillation; Disease-Free Survival; Double-Blind Method; Europe; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Rate; Humans; Incidence; Male; Prospective Studies; Pyridines; Risk Factors; Stroke; Survival Rate; Thiazoles; Time Factors; Treatment Outcome; Vitamin K

The safety of intravenous thrombolysis in patients taking rivaroxaban has not been well established. We retrospectively analyzed the outcomes of all patients who received thrombolytic therapy in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). A review of medical and adverse event records for patients receiving thrombolytic therapy while enrolled in ROCKET AF was performed to determine their baseline characteristics, indications for thrombolysis, and type of agent used. Safety end points were 30-day post-thrombolytic rates of stroke, bleeding, and mortality. A total of 28 patients in ROCKET AF received thrombolytic therapy, with 19 patients on rivaroxaban and 9 patients on warfarin. Ischemic stroke was the most common indication for thrombolysis (n = 10), and alteplase was the most commonly used fibrinolytic agent (n = 14). Of the 19 patients in the rivaroxaban group, there were 2 nonfatal bleeding events and 2 deaths, mostly occurring when thrombolytic therapy was administered within 48 hours of the last rivaroxaban dose. Of the 9 patients in the warfarin group, there was 1 nonfatal bleeding event and 3 deaths, most occurring when thrombolytic therapy was administered outside of 48 hours from the last warfarin dose. In conclusion, these observations suggest that careful assessment of the time since the last dose may be of clinical significance in patients on novel oral anticoagulants who require emergent thrombolysis.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Male; Retrospective Studies; Rivaroxaban; Stroke; Survival Rate; Thrombolytic Therapy; Time Factors; Treatment Outcome; United States; Vitamin K; Warfarin

Eating patterns, food intake and type of alimentation vary greatly during the month of ramadan. Furthermore, fasting, which practiced during the month of ramadan, can have an impact on drug's metabolism. These two factors, fasting and eating habits changes during the month of ramadan, may impact acenocoumarol anticoagulant effect, translated by variations of INR values. The aim of our study was to see ramadan fasting effects on INR variations in patients treated by acenocoumarol. A prospective monocentric study was conducted during the ramadan month on fasting outpatients that were treated by acenocoumarol. Baseline INR values (e.i. most recent available value before the month of ramadan) were compared to INR values obtained during the month of ramadan. All patients were monitored for signs of secondary haemorrhagic complications linked to treatment by anti-vitamin K (AVK). Thirty patients were included in the study with a sex ratio 1. Patients mean age was 65 years. Around two thirds of the patients were treated by AVK for atrial fibrillation. The majority of patients (94%) have been treated by AVK for more than a year. Mean INR was significantly higher during the month of ramadan than baseline (3.51 vs 2.52; p< 0.0001). There were also more overdoses during the month of ramadan than baseline (9 vs. 0; p=0.014). The increased INR values highlights the need of a close monitoring of INR values during the month of ramadan, particularly in patients with a high haemorrhagic risk.

Topics: 4-Hydroxycoumarins; Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Fasting; Female; Hemorrhage; Humans; Indenes; Islam; Male; Middle Aged; Tunisia; Vitamin K

There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients.. Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA. NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH.. In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Female; Humans; Insurance, Health; Male; Republic of Korea; Risk Factors; Stroke; Vitamin K

Oral anticoagulation therapy with vitamin K antagonists (VKA) such as warfarin and acenocoumarol is recommended in patients with atrial fibrillation (AF) and risk factors for embolism. The quality of anticoagulation control with VKA may be assessed by the time in therapeutic range (TTR). In our country, there are no data available about the quality of anticoagulation in patients with AF. The primary goal of our study was to assess the level of effective anticoagulation in a multicenter network of anticoagulation clinics in Argentina, which included patients with nonvalvular AF (NVAF) treated with VKA oral anticoagulants.. The TERRA trial is a multicenter, cross-sectional study involving 14 anticoagulation clinics that were invited to participate and recruit 100 consecutive patients with NVAF treated with VKA for more than 1 year. The international normalized ratio (INR) values were retrospectively obtained from patient charts, and TTR was calculated using the Rosendaal method.. A total of 1190 patients were included in the analysis. Mean age was 74.9 ± 9.9 years, and 52.5% of the patients were male. Median TTR was 67.5% (interquartile interval 54-80). During 55% of the TTR, INR was >3. Interinstitution variability was substantial, with a range of 57.7% ± 17% to 87.7% ± 17%, P < .001. The 10th percentile of TTR was 41%, the 20th percentile was 50%, the 30th was 58%, and the 35th percentile was 60%. In 40% of patients, TTR was <70%.. In this multicenter study, mean TTR values in patients with AF under VKA were similar to those in international therapeutic clinical trials (55%-65%). Marked variations among institutions were observed and, although average results obtained were high, one third of the patients exhibited a TTR below 60%. This cutoff value is conservative according to current recommendations, and guidelines suggest that when management with VKA cannot be improved, patients should be switched to direct oral anticoagulants. The addition of TTR calculation to clinical practice may help improve the quality of oral anticoagulation in patients with AF, thus improving anticoagulation outcomes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Argentina; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Quality Control; Registries; Vitamin K

Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y. Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y. The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66-0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62-0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not.. Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Topics: Aged; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hospitalization; Humans; Male; Rivaroxaban; Stents; Treatment Outcome; Vitamin K

Atrial fibrillation (AF), with a prevalence of 1% to 2%, is the most common cardiac arrhythmia. Without antithrombotic treatment, the annual risk of a cardioembolic event is 5% to 6%. The source of a cardioembolic event is a thrombus, which is usually formed in the left atrial appendage (LAA). Prevention of cardioembolic events involves treatment with anticoagulant drugs: either vitamin K antagonists or, recently, novel oral anticoagulants (NOAC). The other (nonpharmacologic) option for the prevention of a cardioembolic event involves interventional occlusion of the LAA.. To determine whether percutaneous LAA occlusion is noninferior to treatment with NOAC in AF patients indicated for long-term systemic anticoagulation.. The trial will be a prospective, multicenter, randomized noninferiority trial comparing 2 treatment strategies in moderate to high-risk AF patients (ie, patients with history of significant bleeding, or history of cardiovascular event(s), or a with CHA. The PRAGUE-17 trial will determine if LAA occlusion is noninferior to treatment with NOAC in moderate- to high-risk AF patients.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiovascular Diseases; Embolism; Hemorrhage; Humans; Prospective Studies; Quality of Life; Stroke; Vitamin K

Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping.. Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. Objectives To explore possible reasons for the lack of differences between trial arms by performing a secondary analysis of EU-PACT data in order to evaluate the performance of both dosing algorithms across VKORC1-CYP2C9 genetic subgroups. Patients/Methods Anticoagulation control measured according to an International Normalized Ratio (INR) below (INR of < 2), within (INR of 2-3) and above (INR of > 3) the therapeutic range was compared across VKORC1-CYP2C9 subgroups. Owing to a low number of patients in each subgroup, trials for acenocoumarol and phenprocoumon were combined for analysis. Results Four weeks after therapy initiation, genotype-guided dosing increased the mean percentage of time in the therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9*1*1 subgroup as compared with the non-genetic dosing (difference of 14.68%, 95% confidence interval [CI] 5.38-23.98). For the VKORC1 AA-CYP2C9*1*1 subgroup, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (difference of 19.9%; 95% CI 11.6-28.2). Twelve weeks after therapy initiation, no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic subgroups. Conclusions EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose overcautiously in the VKORC1 AA-CYP2C9*1*1 subgroup. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping.

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Data Interpretation, Statistical; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Phenprocoumon; Prospective Studies; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Catheter ablation is the most efficacious rhythm control therapy in atrial fibrillation (AF) patients. There is growing evidence that catheter ablation procedures are best performed during continuous oral anticoagulation, but outcomes are variable depending on the anticoagulation strategy or agent chosen. Specifically, there is a need to evaluate the peri-procedural use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients undergoing catheter ablation of AF. The AXAFA-AFNET 5 trial will test whether peri-procedural anticoagulation therapy using apixaban is a safe alternative to vitamin K antagonist (VKA) therapy for patients undergoing catheter ablation of AF.. AXAFA-AFNET 5 is a randomized, prospective multi-centre study conducted in Europe and the USA. A total of 650 patients scheduled for AF ablation will be randomized 1:1 to undergo AF ablation on continuous treatment with the NOAC apixaban or with a VKA. Patients can undergo AF ablation after at least 30 days of continuous effective anticoagulation or after exclusion of atrial thrombi by transoesophageal echocardiogram. The trial includes a post-ablation magnetic resonance imaging substudy that will quantify silent brain lesions that can occur in neurologically asymptomatic patients after AF ablation. Patients will be followed on continuous anticoagulation for 3 months after the ablation. The primary outcome parameter of AXAFA-AFNET 5 is a composite of all-cause death, stroke, and major bleeding events.. The results of AXAFA-AFNET 5 will provide evidence informing about the safety of apixaban in ablation patients and on its efficacy including effects on silent brain lesions. AXAFA - AFNET 5 is an investigator-initiated trial sponsored by AFNET. The trial is supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research) and by Bristol-Myers Squibb/Pfizer Alliance.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Drug Administration Schedule; Echocardiography, Transesophageal; Europe; Factor Xa Inhibitors; Hemorrhage; Humans; Magnetic Resonance Imaging; Prospective Studies; Pyrazoles; Pyridones; Research Design; Risk Factors; Stroke; Time Factors; Treatment Outcome; United States; Vitamin K

We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures.. The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of £421 and €360 per patient in UK and Italian settings, respectively.. The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Budgets; Canada; Cost Savings; Cost-Benefit Analysis; Drug Costs; Electric Countershock; Europe; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Models, Economic; Patient Satisfaction; Prospective Studies; Rivaroxaban; Stroke; Surveys and Questionnaires; Time Factors; Treatment Outcome; United States; Vitamin K; Warfarin

Atrial fibrillation is the most common arrhythmia. Its management aims to reduce symptoms and to prevent complications through rate and rhythm control, management of concomitant cardiac diseases and prevention of related complications, mainly stroke. The main objective of Effectiveness, Safety and Costs in Atrial Fibrillation (ESC-FA) study is to analyse the drugs used for the management of the disease in real-use conditions, particularly the antithrombotic agents for stroke prevention. The aim of this work is to present the study protocol of phase I of the ESC-FA study and the baseline characteristics of newly diagnosed patients with atrial fibrillation in Catalonia, Spain.. The data source is System for the Improvement of Research in Primary Care (SIDIAP) database. The population included are all patients with non-valvular atrial fibrillation diagnosis registered in the electronic health records during 2007-2012.. A total of 22,585 patients with non-valvular atrial fibrillation were included in the baseline description. Their mean age was 72.8 years and 51.6% were men. The most commonly prescribed antithrombotics were vitamin K antagonists (40.1% of patients) and platelet aggregation inhibitors (32.9%); 25.3% had not been prescribed antithrombotic treatment. Age, gender, comorbidities and co-medication at baseline were similar to those reported for previous studies.. The next phase in the ESC-FA study will involve assessing the effectiveness and safety of antithrombotic treatments, analysing stroke events and bleeding episodes' rates in our patients (rest of phase I), describing the current management of the disease and its costs in our setting, and assessing how the introduction of new oral anticoagulants changes the stroke prevention in non-valvular atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Clinical Protocols; Drug Therapy, Combination; Electronic Health Records; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Decision Support Systems, Clinical; Female; Humans; International Normalized Ratio; Male; Middle Aged; Stroke; Vitamin K; Warfarin

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

Topics: Acute Disease; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Male; Prospective Studies; Stroke; Vitamin K; Warfarin

The efficacy, safety, and ease of use of rivaroxaban may reduce anticoagulation-treatment burden and improve nonvalvular atrial fibrillation (NVAF) patient satisfaction compared with vitamin K antagonists (VKAs).. Transitioning from a VKA to rivaroxaban improves treatment satisfaction in routine practice.. Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation (XANTUS) is a prospective, noninterventional study in patients with NVAF prescribed rivaroxaban for prevention of stroke in routine practice. Patients receiving a VKA 4 weeks prior to the initial XANTUS study visit and switched to rivaroxaban were asked to complete the Anti-Clot Treatment Scale (ACTS). Changes from the initial visit to the first follow-up visit at ∼ 3 months (corresponding to a comparison of rivaroxaban vs prior VKA) for ACTS burden and benefit scores were calculated using and reported as least squared mean differences (LSMDs) with 95% confidence intervals (CIs).. The study included 1291 NVAF patients with prior VKA treatment. The mean baseline ACTS burden and benefit scores were 50.51 ± 8.42 and 10.30 ± 2.70, respectively. After ∼ 3 months of rivaroxaban treatment, LSMDs were 4.38 points (95% CI: 2.53-6.22, P < 0.0001) for the burden and 1.01 points (95% CI: 0.27-1.75, P = 0.0075) for the benefit score. Fifty-four percent and 48% of patients reported experiencing at least a minimally important clinical difference in burden and benefit scores, respectively.. Within this XANTUS cohort, switching from a VKA to rivaroxaban yielded statistically and clinically significant improvements in ACT burden and benefit scores.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Drug Substitution; Factor Xa Inhibitors; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Registries; Rivaroxaban; Stroke; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vitamin K

The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).. The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown.. The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial.. Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups.. In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Disease; Coronary Thrombosis; Double-Blind Method; Drug Substitution; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Embolism; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stroke; Time Factors; Treatment Outcome; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin and heparins in several clinical situations. With varying modes of action, the effects of NOACs on thrombus formation, integrity, and lysis is unknown. To determine whether two techniques of thrombelastography (TEG) and a micro-plate assay (MPA) provide novel data on thrombus formation, integrity and lysis in those taking a NOACs compared to warfarin and a control group taking aspirin. We assessed thrombogenesis, clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients-50 on aspirin, 50 on warfarin, and 82 on a NOAC (17 apixaban, 19 dabigatran and 46 rivaroxaban). Eleven of 16 TEG indices and 4 of 5 MPA indices differed (p ≤ 0.01) between those on aspirin, warfarin or a NOAC. Three TEG indices and 4 MPA indices differed (p < 0.01) between the NOACs. Time to initiation of clot formation was most rapid on apixaban, then rivaroxaban and slowest on dabigatran. The rate of clot formation was most rapid on dabigatran, then apixaban, and slowest on rivaroxaban. Clot density was greatest on rivaroxaban, then apixaban, but weakest on dabigatran. The rate of clot dissolution was most rapid in apixaban, then dabigatran, and slowest on rivaroxaban. The TEG and MPA identify major differences in thrombogenesis and fibrinolysis in different NOACs. These techniques may have value in investigating the effects of these drugs on haemostasis in a clinical setting, and in identifying those in need of targeted therapy.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Fibrin; Humans; Middle Aged; Thrombolytic Therapy; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown.. Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA.. With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.

Topics: Aged; Atrial Fibrillation; Atrial Flutter; Atrial Function, Left; Dabigatran; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Vitamin K

In patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) with placement of stents, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy (DAPT) with a P2Y. We randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y. The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3; hazard ratio for group 1 vs. group 3, 0.59; 95% confidence interval [CI], 0.47 to 0.76; P<0.001; hazard ratio for group 2 vs. group 3, 0.63; 95% CI, 0.50 to 0.80; P<0.001). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan-Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3; P values for all comparisons were nonsignificant).. In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y

Topics: Aged; Atrial Fibrillation; Cardiovascular Diseases; Confidence Intervals; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Stents; Vitamin K

Although non-vitamin K antagonist oral anticoagulants (NOACs) do not require frequent laboratory monitoring, each compound requires dose adjustments on the basis of certain clinical criteria.. This study assessed the frequency of off-label NOAC doses among AF patients and the associations between off-label dose therapy and clinical outcomes in community practice.. We evaluated 5,738 patients treated with a NOAC at 242 ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation phase II) sites. NOAC doses were classified as either underdosed or overdosed, consistent with Food and Drug Administration labeling. Longitudinal outcomes (median follow-up: 0.99 years) included stroke or systemic embolism, myocardial infarction, major bleeding (International Society of Thrombosis and Haemostasis criteria), cause-specific hospitalization, and all-cause mortality.. Overall, 541 NOAC-treated patients (9.4%) were underdosed, 197 were overdosed (3.4%), and 5,000 were dosed according to U.S. labeling (87%). Compared with patients receiving the recommended dose, those who were receiving off-label doses were older (median: 79 and 80 years of age vs. 70 years of age, respectively; p < 0.0001), more likely female (48% and 67% vs. 40%, respectively; p < 0.0001), less likely to be treated by an electrophysiologist (18% and 19% vs. 27%, respectively; p < 0.0001), and had higher CHA. A significant minority (almost 1 in 8) of U.S. patients in the community received NOAC doses inconsistent with labeling. NOAC over- and underdosing are associated with increased risk for adverse events. (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II [ORBIT-AF II]; NCT01701817).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Off-Label Use; Registries; Retrospective Studies; Stroke; Survival Rate; United States; Vitamin K

Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation.. Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6).. In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Morpholines; Prospective Studies; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs).. We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively).. More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hospital Mortality; Humans; Intracranial Hemorrhages; Japan; Male; Retrospective Studies; Vitamin K; Warfarin

Atrial fibrillation (AF) is one of the most common causes of preventable ischemic stroke and is related to increased cardiovascular morbidity and mortality. There is a lack of data in Turkey on the use of new oral anticoagulants (NOACs), and time in therapeutic INR range (TTR) in vitamin K antagonist users and AF management modality. In this multi-center trial, we aimed to analyze, follow and evaluate the epidemiological data in non-valvular AF patients.. Four thousand one hundred consecutive adult patients from 42 centers with at least one AF attack identified on electrocardiography will be included in the study. Patients with rheumatic mitral valve stenosis and prosthetic valve disease will be excluded from the study. At the end of one year, the patients will be evaluated in terms of major cardiac end points (death, transient ischemic attack, stroke, systemic thromboembolism, major bleeding and hospitalization).. First results are expected in June 2015. Data about major cardiovascular end-points will be available in January 2016.. The rates and kind of oral anticoagulant use, TTR in vitamin K antagonist users and main management modality applied in non-valvular AF patients will be determined by AFTER-2 study. In addition, the rate of major adverse events (MACEs) and the independent predictors of these MACEs will be detected (AFTER-2 Study ClinicalTrials.gov number, NCT02354456.).

Topics: Anticoagulants; Atrial Fibrillation; Humans; Turkey; Vitamin K

Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes.. PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial-like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial-like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding).. The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Rivaroxaban; Thiophenes; Ticlopidine; Treatment Outcome; Vitamin K

VENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA).. Trial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar.. In patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy.. Clinicaltrials.gov trial registration number is NCT01729871.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Loss, Surgical; Catheter Ablation; Drug Administration Schedule; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Operative Time; Prospective Studies; Pulmonary Veins; Recurrence; Reoperation; Rivaroxaban; Single-Blind Method; Treatment Outcome; Vitamin K

AZD0837 is a novel oral anticoagulant investigated in clinical studies for stroke prevention in patients with atrial fibrillation (AF). It is bioconverted to its active form, AR-H067637, a potent, specific and reversible thrombin inhibitor. The effects on coagulation biomarkers were correlated with the pharmacokinetic (PK) exposure of AR-H067637 to guide selection of the effective dose regimen for a confirmatory efficacy study in AF patients.. Blood samples were obtained from 601 AF patients randomized to one of four doses of AZD0837 (blinded treatment) or dose-adjusted vitamin K antagonists (VKA, open treatment) for 3-9 months. A pharmacodynamic model was developed to describe the time course of the AR-H067637 exposure dependent effects and the effect of VKA on fibrin D-dimer. The thrombin generation measured ex vivo in venous plasma was also investigated.. The PK exposure of AR-H067637 was stable with an interindividual variability of 33% and no or minor influence of patient demographics or comedications. For AZD0837, D-dimer levels decreased with more rapid onset than for VKA. The decrease in D-dimer levels correlated with steady-state plasma concentrations (C(ss)) of AR-H067637, with a maximum decrease of baseline D-dimer levels estimated to approximately 60% for both AZD0837 and VKA therapy. The effect on thrombin generation correlated closely with the plasma concentration of AR-H067637.. The effects on thrombin generation and fibrin D-dimer levels correlated with the plasma concentration of its active form and provided comparable effects to well-controlled VKA therapy at an exposure at least corresponding to the 300 mg once daily dose of AZD0837.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Amidines; Anticoagulants; Atrial Fibrillation; Azetidines; Biomarkers; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Sex Characteristics; Thrombin; Vitamin K

The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial.. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding.. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients.. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).. The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin.. The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model.. The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk.. Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767).

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Pressure; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Patient Safety; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Time Factors; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs) were developed for the treatment of thromboembolic diseases to overcome limitations of vitamin K antagonists (VKA). International guidelines on atrial fibrillation acknowledge patients' for antiembolic therapy with VKA or DOAC as relevant decision criteria. The objective assessment of patients' preference social interactions and psychological factors are hard to measure albeit representing important contributors. After a series of structured interviews and pilot studies assessing the preparedness to use DOAC as an anticoagulant and the motivation of patients to participate in clinical studies with DOAC, seven items were identified from several questionnaires by regression analysis. Those items were seen the best to describe the willingness to change anticoagulation from VKA to DOAC. By their use, we aim to develop a tool for the objective identification of the patients' preferences for VKA or for DOAC to increase adherence to therapy and to reduce anticoagulant undertreatment. German-speaking patients were asked to fill out a questionnaire consisting of biographic data and the seven selected items, and 180 patients completed the questionnaire so far. Of these, 90 patients were on treatment with VKA (group 1), 57 patients changed anticoagulation from VKA to DOAC (group 2), 29 patients were DOAC naive patients (group 3), and 4 patients changed from DOAC to VKA (group 4). Overall, 94 patients received VKA, 29 patients received dabigatran, 50 patients received rivaroxaban, and 7 patients received apixaban as an anticoagulant. Eight patients were younger than 40 years, 35 patients were aged between 40 and 59 years, 53 patients were aged between 60 and 70 years, and 84 patients were aged older than 70 years. Indication for anticoagulation were atrial fibrillation (n = 106), pulmonary embolism (n = 24), deep vein thrombosis (n = 40), artificial heart valve replacement (n = 8), or other diseases (n = 2). Based on the results of the analysis, a score will be suggested to identify the preference of patients for anticoagulation with VKA or DOAC. This tool may be useful for practitioners and health-care professionals to support patient adherence to therapy, and thereby increase treatment effectiveness.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Practice Guidelines as Topic; Pulmonary Embolism; Surveys and Questionnaires; Venous Thrombosis; Vitamin K

Most evidence regarding the efficacy and safety of the antithrombotic regimens for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention with stent (PCI-S) derives from small, single-center, retrospective datasets. To obtain further data on this issue, we carried out the prospective, multicenter, observational Management of patients with Atrial Fibrillation undergoing Coronary Artery Stenting (AFCAS) registry (Clinicaltrials.gov identifier NCT00596570).. We hypothesize that the antithrombotic treatment of AF patients undergoing PCI-S is variable and the clinical outcome may vary according to the different regimens.. Consecutive AF patients undergoing PCI-S at 17 European institutions were included and followed for 1 year. Outcome measures included: (1) major adverse cardiac/cerebrovascular events (MACCE), including all-cause death, myocardial infarction, repeat revascularization, stent thrombosis, or stroke/transient ischemic attack, and (2) bleeding, and were compared according to the antithrombotic regimen adopted. A propensity-score analysis was carried out to adjust for baseline and procedural differences.. Out of the 975 patients enrolled, 914 were included in the final analysis. The mean CHADS2 score was 2.2 ± 1.2, and 71% of patients had a CHADS2 score ≥2. Triple therapy (TT) of vitamin K antagonist (VKA), aspirin, and clopidogrel was prescribed to 74% of patients, dual antiplatelet therapy to 18%, and VKA plus clopidogrel to 8%. At 1-year follow-up, no significant differences were found in the occurrence of MACCE and bleeding among the 3 antithrombotic regimens, even when adjusted for propensity score.. In this large, real-world population of AF patients undergoing PCI-S, TT was the antithrombotic regimen most frequently prescribed. Although several limitations need to be acknowledged, in our study the 1-year efficacy and safety of TT, dual antiplatelet therapy, and VKA plus clopidogrel was comparable.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Vessels; Female; Fibrinolytic Agents; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Stents; Ticlopidine; Vitamin K

Current stroke risk schemes need improvement of predictive value in patients with atrial fibrillation. Transoesophageal echocardiography (TEE) may facilitate stroke risk assessment in such patients and guide antithrombotic treatment.. We randomised 238 patients with non-valvular atrial fibrillation and a moderate stroke risk to aspirin or adjusted vitamin K antagonist therapy after TEE had ruled out thrombogenic features in the atria and aorta. The primary outcome was a composite of stroke, major bleeding, peripheral embolism and all-cause mortality.. Mean CHA2DS2-VASc score was 2.1±1.1. The incidences of the composite primary outcome at a mean follow-up of 1.6 years were 3.2% (2.02% per year) in the aspirin group compared to 6.1% (3.84% per year) in the vitamin K antagonists group with an absolute advantage of 2.9 percentage points. Aspirin was non-inferior to vitamin K antagonists (p<0.0001) because the upper limit of the 90% CI did not exceed the 7% absolute difference in event rate between the two treatment arms.. This hypothesis-generating pilot trial has found that TEE may be used for refinement of stroke risk in paroxysmal atrial fibrillation patients. A larger trial is needed to confirm these data. (ClinicalTrials.gov number NTC00224757).

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Humans; Male; Pilot Projects; Prospective Studies; Risk Assessment; Stroke; Vitamin K

During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI.. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32).. TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation.. http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Prospective Studies; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

The AVERROES double-blinded, randomized trial demonstrated that apixaban reduces the risk of stroke or systemic embolism (SSE) by 55% compared with aspirin without an increase in major bleeding in patients with atrial fibrillation either who previously tried but failed vitamin K antagonists (VKA) therapy or who were expected to be unsuitable for VKA therapy. In this pre-specified analysis, we explored the consistency of the results in the subgroup of patients who tried but failed VKA therapy.. Of 5599 patients, 2216 (40%) had previously failed VKA treatment [main reasons: poor international normalized ratio (INR) control 42%, refusal 37%, bleeding on VKA 8%]. Compared with those expected to be unsuitable for VKA therapy, those who had previously failed were older, more often male, had higher body mass index, more likely to have moderate renal impairment and a history of stroke and less likely to have heart failure or to be medically undertreated. The effects of apixaban compared with aspirin were consistent in those who previously failed and those who were expected to be unsuitable, for both SSE (P interaction 0.13) and major bleeding (P interaction 0.74) and were also consistent among different subgroups of patients who had previously failed VKA therapy defined by reasons for unsuitability, age, sex, renal function, CHADS2 score, aspirin dose, duration, indication, and quality of INR control of prior VKA use.. The efficacy and safety of apixaban compared with aspirin is consistent in subgroups of patients who have previously attempted but failed VKA therapy, irrespective of the reason for discontinuation.

Topics: Aged; Aspirin; Atrial Fibrillation; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Idrabiotaparinux, a long-acting inhibitor of factor Xa, was shown to be effective in the treatment of patients with venous thromboembolism.. To assess non-inferiority for the efficacy of idrabiotaparinux versus warfarin in patients with atrial fibrillation (AF) at risk of stroke and systemic embolism. Bleeding was also assessed.. This randomized, double-blind trial enrolled patients with electrocardiogram-documented AF. Idrabiotaparinux was administered weekly via subcutaneous injection, and warfarin was administered daily with dose adjustment to maintain the international normalized ratio between 2.0 and 3.0. Each idrabiotaparinux injection was 3 mg for the first 7 weeks, followed by 2 mg thereafter, except in patients with a creatinine clearance of 30-50 mL min(-1) or aged ≥ 75 years. The patients received 1.5 mg after the first 7 weeks. The efficacy outcome was the composite of all fatal or non-fatal strokes and systemic embolism. The safety outcome was clinically relevant bleeding (major and clinically relevant non-major bleeding).. The study was terminated prematurely by the sponsor for strategic/commercial, not scientific, reasons, with 39% of the planned number of patients included and an average duration of treatment of 240 days. Of the 1886 idrabiotaparinux recipients, 20 developed stroke or systemic embolism (1.5% per year), whereas this occurred in 22 of the 1887 warfarin patients (1.6% per year, hazard ratio 0.98, 95% confidence interval 0.49-1.66). The annual incidence of bleeding was 6.1% in the idrabiotaparinux and 10.0% in the warfarin group (hazard ratio 0.61, 95% confidence interval 0.46-0.81).. If anything, despite its early termination, the idrabiotaparinux regimen studied suggested a comparable efficacy to dose-adjusted warfarin, with a lower bleeding risk.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biotin; Double-Blind Method; Drug Administration Schedule; Early Termination of Clinical Trials; Electrocardiography; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Oligosaccharides; Predictive Value of Tests; Risk Factors; Stroke; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors.. Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11).. Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Transfusion; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Hospitalization; Humans; Male; Morpholines; Plasma; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation.. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used.. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73).. Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Topics: Aged; Anticoagulants; Asian People; Atrial Fibrillation; Black People; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Morpholines; Prospective Studies; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

Anticoagulation before, during, and after cardioversion is effective in reducing stroke risk in patients with atrial fibrillation.. The objective of this study is to explore the efficacy and safety of rivaroxaban 20 mg once daily (15 mg if creatinine clearance is 30-49 mL/min) compared with dose-adjusted vitamin K antagonists (VKAs; international normalized ratio 2.0-3.0) in patients scheduled for elective cardioversion.. This is a prospective, randomized, open-label, parallel group comparison of approximately 1,500 patients from 17 countries with hemodynamically stable nonvalvular atrial fibrillation of >48 hours or unknown duration. Patients will be randomized 2:1 (rivaroxaban:VKA) using 2 cardioversion strategies: the first approach is early cardioversion with the precardioversion anticoagulation goal of 1 to 5 days using rivaroxaban or usual therapy (heparin + VKA). In these patients, transesophageal echocardiography will be encouraged to exclude atrial thrombi. The alternative approach is delayed cardioversion. Rivaroxaban or VKA will be administered for 21 to 56 days before cardioversion. All patients will receive study treatment for 6 weeks postcardioversion. The primary efficacy end point is a composite of all strokes, transient ischemic attacks, noncentral nervous system systemic emboli, myocardial infarctions, and cardiovascular deaths. Each primary end point component will be evaluated separately, and additional composites will be investigated. The principal safety end point is major bleeding.. This will be the first prospective study of a novel oral anticoagulant in the setting of cardioversion. It will provide important information regarding the use of rivaroxaban in the periods preceding and after cardioversion in a broad patient population.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Double-Blind Method; Echocardiography, Transesophageal; Electric Countershock; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Morpholines; Prospective Studies; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Vitamin K

Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). This prespecified secondary analysis compares outcomes in older and younger patients.. There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response.. Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

D-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases.. To evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin.. In the ARISTOTLE trial, 18 201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14 878 patients at randomization. The cohort was separated into two groups; not receiving vitamin K antagonist (VKA) treatment and receiving VKA treatment at randomization.. Higher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR] [Q4 vs. Q1] 1.72, 95% confidence interval [CI] 1.14-2.59, P = 0.003), death (HR [Q4 vs. Q1] 4.04, 95% CI 3.06-5.33) and major bleeding (HR [Q4 vs. Q1] 2.47, 95% CI 1.77-3.45, P < 0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS2 score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level.. In anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Embolism; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Male; Middle Aged; Predictive Value of Tests; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

The incidence of atrial fibrillation (AF) and of thromboembolic complications increases along with age. This is also the case for cognitive function disturbances; therefore their occurrence in patients (pts) with AF may hamper control of anticoagulant therapy and maintenance of therapeutic INR values. The aim of the study was to evaluate the effect of cognitive function disturbances on implementation and monitoring of the treatment with oral vitamin K antagonists (VKA) in patients with AF. The relationship between the level of cognitive function disturbances and the severity of experienced AF symptoms was defined.. The analysis included a group of 93 pts (41 males, 52 females, mean age: 76.8) with a diagnosis of AF and with indications for anticoagulation treatment with VKAs (CHA2DS2VASc > or = 2, HAS-BLED < 3), referred to the Clinic of Internal Diseases and Clinical Pharmacology of the Medical University of Lodz. In a group of pts (n = 46) treated chronically with VKAs, mean INR values at admission to the hospital were calculated and the number of results falling within the therapeutic range of 2-3, by the severity of cognitive disturbances, was analyzed. Cognitive abilities were assessed with the Mini Mental State Examination Scale (MMSE) (MMSE-Mini-mental state examination). The EHRA (European Heart Rhythm Association) classification was used to assess AF-related complaints.. The 93 studied subjects were divided into 3 groups: group I with normal cognitive function (MMSE = 24-27) - n = 35; group II with disturbances of cognitive function without dementia (MMSE = 24-26) - n = 35 and group III with dementia (MMSE < 24) - n = 23.66% of pts with normal MMSE result were referred to the hospital because AF-related symptoms and in the group of patients with MMSE < 24 these symptoms were the cause of hospitalization in 23% of pts. Despite the fact that all patients had indications for VKAs, this treatment was not started in 40%, 51.4% and 65% of pts in group I, II and III, respectively. At admission to the hospital, therapeutic level INR values were found only in 34.8% of AF pts. 49% of pts were treated with VKAs in total. In group II, a high percentage of patients (43%) treated with aspirin was found in spite of high thromboembolic risk and no contraindications to VKAs. About 23% of pts with a normal MMSE result and 14% of pts in group II experienced AF-related symptoms preventing them from normal functioning and performing daily activities (EHRA IV). Nobody in group III reported severe AF-related symptoms.. Along with the advancing age, there is an increase of the incidence of persistent and fixed atrial fibrillation, of the risk of thromboembolic complications and of the severity of cognitive function disturbances. Treatment with oral vitamin K antagonists was implemented much less frequently among patients with atrial fibrillation and cognitive function disturbances, as compared to the patients with normal cognitive function. The MMSE test should be routinely performed in patients with atrial fibrillation to monitor the efficacy and safety of the treatment with oral vitamin K antagonists properly. In patients with disturbances of cognitive function, significantly lower reportability of AF-related complaints was shown, as compared to individuals without these disturbances. Patients with normal MMSE result were referred to the hospital because AF-related symptoms, in the group of patients with MMSE < 23 the main reason for hospitalization was the severity of the symptoms heart failure. ECG should be a routine test performed in elderly patients with cognitive function disturbances or with dementia to detect atrial fibrillation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cognition Disorders; Comorbidity; Dementia; Drug Monitoring; Drug Utilization; Electrocardiography; Female; Humans; Incidence; Male; Middle Aged; Thromboembolism; Vitamin K

To evaluate the safety of uninterrupted rivaroxaban, a novel oral anticoagulant that directly inhibits factor Xa, and a vitamin K antagonist (VKA) in eligible adult patients with nonvalvular AF (NVAF) who are scheduled for a catheter ablation.. This is a prospective, randomized, open-label, active-controlled, global multicenter safety study of up to 250 randomized patients. Eligible patients with paroxysmal or persistent NVAF, a left ventricular ejection fraction >40 %, and a creatinine clearance >50 mL/min will be randomized 1:1 to rivaroxaban 20 mg orally once daily or to dose-adjusted oral VKA (recommended international normalized ratio (INR) 2.0-3.0) and stabilized on anticoagulation therapy for 1-7 days (if no intracardiac thrombus on transesophageal echocardiogram (TEE) immediately prerandomization/post-randomization or if 3 weeks of sufficient anticoagulation is documented) or for 4-5 weeks (if no TEE, no documented 3 weeks of sufficient anticoagulation, or by patient choice). During catheter ablation, heparin will be administered (ACT-targeted range = 300-400 s) after catheter ablation, and VKA will be managed per usual care. The next dose of rivaroxaban will be provided at least 6 h after establishment of hemostasis. The primary endpoint will be the incidence of post-procedure major bleeding events observed during the first 30 ± 5 days post-ablation. Secondary endpoints will include post-procedure thromboembolic events, additional bleeding, time-to-event, and medication adherence.. This study is intended to provide information about the safety characteristics of rivaroxaban in patients with NVAF undergoing catheter ablation.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Patient Safety; Postoperative Care; Preoperative Care; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Statistics, Nonparametric; Survival Rate; Thiophenes; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

X-VeRT is the first prospective randomized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion.. We assigned 1504 patients to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted vitamin K antagonists (VKAs) in a 2:1 ratio. Investigators selected either an early (target period of 1-5 days after randomization) or delayed (3-8 weeks) cardioversion strategy. The primary efficacy outcome was the composite of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, and cardiovascular death. The primary safety outcome was major bleeding. The primary efficacy outcome occurred in 5 (two strokes) of 978 patients (0.51%) in the rivaroxaban group and in 5 (two strokes) of 492 patients (1.02%) in the VKA group [risk ratio 0.50; 95% confidence interval (CI) 0.15-1.73]. In the rivaroxaban group, four patients experienced primary efficacy events following early cardioversion (0.71%) and one following delayed cardioversion (0.24%). In the VKA group, three patients had primary efficacy events following early cardioversion (1.08%) and two following delayed cardioversion (0.93%). Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs (P < 0.001). Major bleeding occurred in six patients (0.6%) in the rivaroxaban group and four patients (0.8%) in the VKA group (risk ratio 0.76; 95% CI 0.21-2.67).. Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion.. Clinicaltrials.gov;. NCT01674647.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Electric Countershock; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Treatment Outcome; Vitamin K

To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist.. At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42; warfarin 6 events, event rate 1.73; hazard ratio, 3.72; 95% confidence interval, 1.51-9.16; P=0.0044). No INR values were reported for ≈5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had ≥1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group.. The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Clinical Protocols; Continuity of Patient Care; Double-Blind Method; Drug Administration Schedule; Drug Substitution; Embolism; Factor Xa; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Male; Middle Aged; Morpholines; Proportional Hazards Models; Research Design; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Time Factors; Treatment Outcome; Vitamin K; Warfarin

In ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), a large randomized, clinical trial, rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation.. To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients.. Prespecified subgroup analysis. (ClinicalTrials.gov: NCT00403767).. Global.. 14,264 persons with atrial fibrillation.. Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients.. Overall, 7897 (55.4%) patients were VKA-experienced and 6367 (44.6%) were VKA-naive. The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent: Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients (hazard ratio [HR], 0.81 [95% CI, 0.64 to 1.03]) and 1.98 versus 2.09 for VKA-experienced patients (HR, 0.94 [CI, 0.75 to 1.18]; interaction P = 0.36). During the first 7 days, rivaroxaban was associated with more bleeding than warfarin (HR in VKA-naive patients, 5.83 [CI, 3.25 to 10.44], and in VKA-experienced patients, 6.66 [CI, 3.83 to 11.58]; interaction P = 0.53). After 30 days, rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients (HR, 0.84 [CI, 0.74 to 0.95]) and similar bleeding in VKA-experienced patients (HR, 1.06 [CI, 0.96 to 1.17]; interaction P = 0.003).. The trial was not designed to detect differences in these subgroups.. The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial. There were more bleeding events within 7 days of study drug initiation with rivaroxaban, but after 30 days, rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients. This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy.. Johnson & Johnson and Bayer HealthCare.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comparative Effectiveness Research; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

Limited data are available on the impact of renal function on the outcome of patients with atrial fibrillation (AF).. AMADEUS was a multicentre, randomized, open-label non-inferiority study that compared fixed-dose idraparinux with conventional anticoagulation by dose-adjusted vitamin K antagonists. We performed a post hoc analysis to assess the impact of renal function on the outcomes of anticoagulated AF patients. The primary efficacy outcome was the composite of stroke/systemic embolism (SE). The principal safety outcome of this analysis was major bleeding. We calculated c-indexes, reflecting the ability for discriminating diseased vs. non-diseased patients, and the net reclassification improvement (NRI, an index of inferior/superior performance of risk estimation scores). Of 4576 patients, 45 strokes and 103 major bleeding events occurred following an average follow-up of 325 ± 164 days. Patients with CrCl >90 mL/min had an annual stroke/SE rate of 0.6% compared with 0.8% for those with CrCl 60-90 mL/min and 2.2% for those with CrCl <60 mL/min (P < 0.001 for linear association). After adjusting for stroke risk factors, patients with CrCl <60 mL/min had more than two-fold higher risk of stroke/SE and almost 60% higher risk of major bleeding compared with those with CrCl ≥60. In patients with the CHA2DS2VASc score 1-2, CrCl <60 mL/min was associated with eight-fold higher stroke risk. When added to the CHA2DS2VASc or CHADS2 scores, CrCl <60 mL/min did not improve the c-indexes for CHADS2 (P = 0.054) or CHA2DS2VASc (P = 0.63) but resulted in significant NRI (0.26, P = 0.02) in this anticoagulated trial cohort.. Renal impairment (CrCl <60 mL/min) doubles the risk of stroke and increased the risk of major bleeding by almost 60% in anticoagulated patients with AF. Renal impairment was additive to stroke risk prediction scores based on a significant NRI, but no significant improvement in discrimination ability (based on c-indexes) for CHA2DS2VASc or CHADS2 was observed.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Oligosaccharides; Renal Insufficiency, Chronic; Risk Assessment; ROC Curve; Stroke; Vitamin K

We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial.. In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2).. In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function.. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa; Female; Follow-Up Studies; Humans; Incidence; Male; Morpholines; Predictive Value of Tests; Reproducibility of Results; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

AZD0837 and ximelagatran are oral direct thrombin inhibitors that are rapidly absorbed and bioconverted to their active forms, AR-H067637 and melagatran, respectively. This study investigated the antithrombotic effect of AZD0837, compared to ximelagatran and the vitamin K antagonist (VKA) phenprocoumon (Marcoumar), in a disease model of thrombosis in patients with non-valvular atrial fibrillation (NVAF).. Open, parallel-group studies were performed in NVAF patients treated with VKA, which was stopped aiming for an international normalized ratio (INR) of ≤ 2 before randomization. Study I: 38 patients randomized to AZD0837 (150,250 or 350 mg) or ximelagatran 36 mg twice daily for 10-14 days. Study II: 27 patients randomized to AZD0837 250 mg twice daily or VKA titrated to an INR of 2-3 for 10-14 days. A control group of 20 healthy elderly subjects without NVAF or anticoagulant treatment was also studied. Size of thrombus formed on pig aorta strips was measured after a 5-minute perfusion at low shear rate with blood from the patient/control subject.. Thrombus formation was inhibited by AZD0837 and ximelagatran. Relative to untreated patients, a 50% reduction of thrombus size was estimated at plasma concentrations of 0.6 and 0.2 μmol/L for AR-H067637 and melagatran, respectively. For patients receiving VKA treatment, the thrombus size was about 15% lower compared with healthy elderly controls.. Effects of AZD0837 and ximelagatran on thrombus formation were similar or greater than for VKA therapy and correlated with plasma concentrations of their active forms.

Topics: Administration, Oral; Aged; Amidines; Animals; Anticoagulants; Antithrombins; Atrial Fibrillation; Azetidines; Benzylamines; Female; Humans; In Vitro Techniques; Male; Middle Aged; Swine; Thrombosis; Treatment Outcome; Vitamin K

Evidence on new-onset atrial fibrillation in high-risk vascular patients without heart failure is limited. New-onset atrial fibrillation was a prespecified secondary objective of the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) studies.. We studied 30 424 ONTARGET/TRANSCEND patients (mean age ± SD, 66.4 ± 7.0) with vascular disease or complicated diabetes who were in sinus rhythm at entry. A copy of ECG was sent to central office every time new atrial fibrillation was detected by investigators.. During a median follow-up period of 4.7 years, new atrial fibrillation occurred in 2092 patients (15.1 per 1000  patient-years). Risk of atrial fibrillation increased with age, SBP and pulse pressure, left ventricular hypertrophy, BMI, serum creatinine and history of hypertension, coronary artery disease and cerebrovascular disease (all P < 0.01). After adjustment for BMI and other variables, atrial fibrillation risk increased with hip circumference. History of hypertension was associated with a 34% higher risk of new atrial fibrillation. New atrial fibrillation portended an increased risk of congestive heart failure [hazard ratio 2.89, 95% confidence interval (CI) 2.45-3.40, P < 0.01] and cardiovascular death (hazard ratio 1.22, 95% CI 1.05-1.41, P < 0.01). Risk of stroke was unaffected (hazard ratio 1.14, 95% CI 0.93-1.40), whereas that of myocardial infarction was reduced (hazard ratio 0.64, 95% CI 0.50-0.82). Patients with new atrial fibrillation were more likely to receive vitamin K antagonists (P < 0.01), statins (P < 0.05) and β-blockers (P < 0.01) than those in sinus rhythm.. New atrial fibrillation is common in high-risk vascular patients and is associated with several risk factors including history of hypertension. Hip circumference was the strongest anthropometric predictor. Despite extensive use of modern therapies, new atrial fibrillation carries a high risk of congestive heart failure and death over a relatively short term.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Anthropometry; Atrial Fibrillation; Benzimidazoles; Benzoates; Body Mass Index; Cardiovascular Diseases; Diabetes Complications; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Male; Middle Aged; Placebos; Ramipril; Risk; Risk Factors; Stroke; Telmisartan; Vitamin K

Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy. This analysis explores patterns of bleeding and defines bleeding risks based on stroke risk with apixaban and aspirin.. The Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) trial randomized 5599 patients with atrial fibrillation and risk factors to receive either apixaban or aspirin. Bleeding events were defined as the first occurrence of either major bleeding or clinically relevant nonmajor bleeding.. The rate of a bleeding event was 3.8%/year with aspirin and 4.5%/year with apixaban (hazard ratio with apixaban, 1.18; 95% CI, 0.92-1.51; P=0.19). The anatomic site of bleeding did not differ between therapies. Risk factors for bleeding common to apixaban and aspirin were use of nonstudy aspirin>50% of the time and a history of daily/occasional nosebleeds. The rates of both stroke and bleeding increased with higher CHADS2 scores but apixaban compared with aspirin was associated with a similar relative risk of bleeding (P interaction 0.21) and a reduced relative risk of stroke (P interaction 0.37) irrespective of CHADS2 category.. Anatomic sites and predictors of bleeding are similar for apixaban and aspirin in these patients. Higher CHADS2 scores are associated with increasing rates of bleeding and stroke, but the balance between risks and benefits of apixaban compared with aspirin is favorable irrespective of baseline stroke risk. Clinical Trial Registration Information- www.clinicaltrials.gov. Unique identifier: NCT 00496769.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; Contraindications; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Risk Factors; Stroke; Vitamin K; Warfarin

Oral anticoagulation is the mainstay of therapy for stroke prevention in patients with atrial fibrillation. Vitamin K antagonists such as warfarin reduce the risk of cardioembolic stroke by approximately two-thirds compared with no treatment, but are limited by their unpredictable anticoagulant effect and narrow therapeutic index. Warfarin therapy requires routine coagulation monitoring, which is inconvenient for patients and costly for the healthcare system. The limitations of the vitamin K agonists have spurred the development of new oral anticoagulants that selectively inhibit thrombin or factor Xa. The Randomized Evaluation of Long-Term Anticoagulation (RE-LY) trial of 18,113 patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke demonstrated that dabigatran etexilate given at a dose of 150 mg twice daily compared with warfarin, reduced the rate of stroke or systemic embolism by one-third with a similar rate of major bleeding, whereas dabigatran etexilate given at a dose of 110 mg twice daily compared with warfarin had a similar rate of stroke or systemic embolism and reduced the rate of major bleeding by one-fifth. Both doses of dabigatran etexilate reduced intracranial bleeding by approximately two-thirds compared with warfarin. Based on the results of the RE-LY trial, both the US FDA and Health Canada recently approved dabigatran etexilate for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Embolism; Follow-Up Studies; Humans; Prospective Studies; Pyridines; Risk Factors; Stroke; Vitamin K; Warfarin

Adding clopidogrel to aspirin therapy reduces stroke in patients with atrial fibrillation (AF) but increases hemorrhage.. To quantify the net benefit of adding clopidogrel to aspirin therapy, accounting for differences in clinical significance between ischemic and hemorrhagic events.. Observational cohort study to assign the relative weighting of events and post hoc analysis of randomized trial data to assess net benefit of dual antiplatelet therapy in the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) clinical trials.. Global randomized clinical trial.. 10,041 patients with AF, 7554 of whom were not candidates for warfarin therapy.. Ischemic events (ischemic stroke or myocardial infarction) and hemorrhagic events (hemorrhagic stroke or subdural or extracranial bleeding), weighted by the hazard ratio for death (or death or disability) after an event relative to death (or death or disability) after ischemic stroke. The net clinical benefit of dual antiplatelet therapy in the ACTIVE A trial participants was defined as the sum of weighted event incidence with dual antiplatelet therapy subtracted from the sum of weighted event incidence on control treatment, expressed as ischemic stroke equivalents prevented per 100 patients years.. Adding clopidogrel to aspirin therapy prevented 0.57 ischemic stroke equivalent (95% CI, -0.12 to 1.24) per 100 patient-years of treatment when weighted by hazard for death after ischemia or hemorrhage and 0.67 ischemic stroke equivalent (CI, -0.03 to 1.18) when weighted by death or disability after ischemia or hemorrhage.. No attempt was made to relate deaths used for weighting to events; disability data were missing for more than one half of patients.. Adding clopidogrel to aspirin therapy resulted in a modest net benefit among patients with AF for whom warfarin was unsuitable. The benefit would probably be clinically relevant for some patients, but estimates could not exclude the possibility of either no benefit or very small harm in this population.. Bristol-Myers Squibb and sanofi-aventis.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Sensitivity and Specificity; Stroke; Ticlopidine; Vitamin K

Many patients with atrial fibrillation (AF) at moderate or high risk for stroke are not treated with a vitamin K antagonist (VKA). Presently, the only alternative to a VKA with a labeled indication for AF is antiplatelet therapy with acetylsalicylic acid (ASA), which is much less effective than a VKA for prevention of stroke. The novel oral factor Xa inhibitor, apixaban, is being developed for prevention of stroke in AF. A noninferiority trial of apixaban versus a VKA (warfarin) is being conducted but does not address the large unmet need of AF patients at risk of stroke who are unsuitable for or unwilling to take a VKA. Apixaban may be an attractive alternative to ASA for prevention of stroke in patients with AF who cannot or will not take a VKA.. AVERROES is a double-blind, double-dummy superiority trial of apixaban 5 mg twice daily (2.5 mg twice daily in selected patients) compared with ASA 81 to 324 mg once daily in patients with AF and at least 1 risk factor for stroke who have failed or are unsuitable for VKA therapy. The primary outcome is stroke or systemic embolism, and the primary safety outcome is major bleeding. The trial is event driven and is expected to enroll at least 5,600 patients.. By evaluating the use of apixaban as a replacement for ASA in AF patients who are not treated with a VKA, the AVERROES study is addressing an important unmet clinical need. The results of AVERROES will be complementary to those of a parallel noninferiority trial comparing apixaban with VKA therapy in patients with AF who are able to receive a VKA.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Double-Blind Method; Drug Administration Schedule; Fibrinolytic Agents; Hemorrhage; Humans; Middle Aged; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Research Design; Retreatment; Stroke; Treatment Failure; Vitamin K; Warfarin

Atrial fibrillation (AF), the most common significant cardiac arrhythmia, increases the risk of stroke, particularly in the elderly. Warfarin is effective in reducing stroke risk but is burdensome to patients and is difficult to control. Rivaroxaban is an oral direct factor Xa inhibitor in advanced development as an alternative to warfarin for the prevention and treatment of thromboembolic disorders.. ROCKET AF is a randomized, double-blind, double-dummy, event-driven trial, which aims to establish the noninferiority of rivaroxaban compared with warfarin in patients with nonvalvular AF who have a history of stroke or at least 2 additional independent risk factors for future stroke. Patients are randomly assigned to receive rivaroxaban, 20 mg once daily (od), or dose-adjusted warfarin titrated to a target international normalized ratio (INR) of 2.5 (range 2.0-3.0, inclusive) using point-of-care INR devices to receive true or sham INR values, depending on the study drug allocation. The primary efficacy end point is a composite of all-cause stroke and noncentral nervous system systemic embolism. The primary safety end point is the composite of major and clinically relevant nonmajor bleeding events. Over 14,000 patients have been randomized at 1,100 sites across 45 countries, and will be followed until 405 primary outcome events are observed.. The ROCKET AF study will determine the efficacy and safety of rivaroxaban as an alternative to warfarin for the prevention of thromboembolism in patients with AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Drug Administration Schedule; Embolism; Factor Xa Inhibitors; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Medical Records; Morpholines; Research Design; Risk Factors; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Vitamin K; Warfarin

To assess the risk of death after the occurrence of different types of non-fatal events in patients with atrial fibrillation (AF). Antithrombotic therapies in AF have primarily focused on stroke prevention and bleeding. However, strokes and bleeds differ in severity, and the level of severity may differently impact mortality.. We analysed the risk of subsequent mortality after the occurrence of non-fatal vascular and bleeding events in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE)-W trial. In the 3371 patients randomized to vitamin K antagonists and the 3335 patients randomized to clopidogrel plus aspirin in ACTIVE-W, the hazard ratio (HR) and 95% confidence intervals (95% CIs) for subsequent death associated with the occurrence of non-fatal stroke was 5.58 (95% CI 3.84-8.10, P < 0.0001). Both ischaemic (HR 5.29, 95% CI 3.53-7.93, P < 0.0001) and haemorrhagic strokes (HR 7.38, 95% CI 2.74-19.9, P < 0.0001) increased mortality, but transient ischaemic attacks did not. Disabling strokes (Rankin's score > or =3) increased mortality (HR 9.54; 95% CI 6.42-14.2, P< 0.0001), but non-disabling strokes did not. Severe bleeding increased mortality (HR 3.35, 95% CI 2.12-5.27, P < 0.0001), but major bleeding that was not severe according to the study definitions did not.. Non-fatal strokes increased mortality in ACTIVE-W, but non-disabling strokes did not. Among major bleeding events, only those also classified as severe increased mortality. Future research should emphasize the prevention of disabling strokes and severe bleeds and place less emphasis on non-disabling stroke or major bleeds that are not severe.

Topics: Aspirin; Atrial Fibrillation; Biphenyl Compounds; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Irbesartan; Kaplan-Meier Estimate; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Tetrazoles; Ticlopidine; Treatment Outcome; Vitamin K

The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.. Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.. Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Embolism; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyridines; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.. A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non-central nervous system systemic embolism, or death from vascular causes.. At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).. In patients with atrial fibrillation for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00249873.)

Topics: Aged; Aspirin; Atrial Fibrillation; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk; Stroke; Ticlopidine; Vascular Diseases; Vitamin K

Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF.. Atrial fibrillation patients (n = 955) with > or =1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naïve to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). d-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naïve subjects with treatment, whereas in VKA pre-treated patients, d-dimer levels started low and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by approximately 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase > or =3x upper limit of normal was similar for AZD0837 and VKA.. AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA. This study is registered with ClinicalTrials.gov, number NCT00684307.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Biomarkers; Bleeding Time; Embolism; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Stroke; Thrombin; Vitamin K

Tecarfarin (ATI-5923) is a novel oral vitamin K antagonist. Unlike warfarin, it is metabolized by esterases, escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450-mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system. Both tecarfarin and warfarin can be monitored with the international normalized ratio. We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin.. This was a 6- to 12-week open-label, multicenter, phase IIA study of 66 atrial fibrillation patients with a mild to moderate risk of stroke to determine the safety and tolerability of tecarfarin and to ascertain an optimal tecarfarin dosing regimen. Sixty-four subjects (97%) were taking warfarin at enrollment and were switched to tecarfarin. After the initial 3 weeks of tecarfarin treatment, the mean interpolated time in therapeutic range was 71.4%. Only 10.9% of patients had time in therapeutic range of <45%. Times in extreme international normalized ratio ranges of <1.5 and >4.0 were 1.2% and 1.2%, respectively. The median daily dose (for an individual patient) to maintain an international normalized ratio between 2 and 3 was 15.6 mg (range, 6 to 29 mg).. This is the first study of tecarfarin in patients with atrial fibrillation. It appears that tecarfarin may possess advantages over the currently available standard of care, warfarin, by improving time in therapeutic range. Adequately powered prospective trials are warranted to definitively compare tecarfarin with warfarin in clinical settings for which warfarin is indicated.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Blood Coagulation Factors; Cytochrome P-450 CYP2C9; Female; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Vitamin K; Vitamin K Epoxide Reductases

The objective was to determine the main parameters taken into account for the decision of antithrombotic treatment of atrial fibrillation (AF) by vitamin K antagonist or aspirin. This was a prospective clinical study of four clinical services of geriatric medicine. Two hundred and nine inpatients, 84.7 +/- 7 years (women 60.8%), with chronic AF were included. The patients were distributed into two groups (anticoagulant or aspirin) according to medical decision. All the decision criteria for treatment were recorded: cardiopathy, conditions of life, clinical examination (nutrition and autonomy, mini-mental state examination (MMSE), walking evaluation, comorbidity), subjective evaluation of risk of falls and glomerular filtration rate. The thromboembolic risk and the bleeding risk, evaluated subjectively for each patient, were compared with two scores of thrombo-embolic risk and bleeding risk. The evolution of the patients was recorded after 3 months. Student's t-test and chi-squared tests were used for statistical analysis. One hundred and two patients (48.8%) received anticoagulant and 107 patients received aspirin. Patients in the aspirin group were significantly older (86.5 +/- 6.5 vs. 82.9 +/- 7.1 years), with more frequent social isolation, higher systolic blood pressure, and had more important subjective bleeding risk and risk of falls. Patients in the anticoagulant group had significantly more valvulopathies and a more important subjective thromboembolic risk. Thrombo-phlebitis antecedents, dementia, denutrition and walking alterations were only slightly more frequent in patients in the aspirin group. Physicians underestimated thromboembolic risk (one-third of patients) and they overestimated bleeding risk (half of the patients). After 3 months, the two groups did not significantly differ for death, bleeding or ischaemic events. In common practice, the decision of antithrombotic treatment for AF should take into account not only cardiovascular but also geriatric criteria.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Risk Factors; Vitamin K

Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists.. Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655.. The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD 5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; p<0.0001). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0.014); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0.9 vs 1.3 per 100 patient-years; hazard ratio 0.71, 95% CI 0.39-1.30; p=0.007), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3.2 vs 2.9 per 100 patient-years; p=0.49).. In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Oligosaccharides; Risk Factors; Single-Blind Method; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Canada; Double-Blind Method; Hemorrhage; Humans; Risk; Stroke; Thrombin; Treatment Outcome; United States; Vitamin K; Warfarin

When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital.. This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths.. Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

Topics: Anticoagulants; Arterial Occlusive Diseases; Aspirin; Atrial Fibrillation; Blood Loss, Surgical; Cohort Studies; Dalteparin; Elective Surgical Procedures; Feasibility Studies; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Intraoperative Complications; Postoperative Complications; Postoperative Hemorrhage; Premedication; Preoperative Care; Prospective Studies; Risk; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

During commencement of oral anticoagulant therapy (OAT) a theoretical possibility of a transient hypercoagulable state emerges from the difference in plasma half-life between the vitamin K-dependent pro-coagulation factors II and X, and the vitamin K-dependent anticoagulant proteins C and S. In the present study, markers reflecting the activity in the haemostatic system (prothrombin fragment 1+2 [F1+2], D-dimer and soluble fibrin) was assessed during initiation of OAT compared to subcutaneously administered low-molecular weight heparin (LMWH) which does not cause any imbalance between the concentrations of the pro- and anticoagulation proteins.. Thirty-three patients with atrial fibrillation were randomly treated either with OAT (warfarin 10, 7.5, and 5 mg for three consecutive days) or LMWH administered in a fixed dose of 200 anti-Xa IU/kg body weight in one subcutaneous injection daily. The biochemical markers were measured at baseline, and after 12, 36 and 60 h of treatment.. After introducing antithrombotic therapy, none of the biochemical markers increased within the study period in the two treatment groups. The level of F1+2 had declined significantly at 60 h in both groups. The level of soluble fibrin showed a significant decrease within the first 60 h in the OAT group, and no significant changes were seen in the LMWH group. No significant change in the level of D-dimer was seen during the first 60 h of treatment in either group. Taken together, no transient hypercoagulable state could be identified within the first 60 h of commencing OAT in patients with atrial fibrillation.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Biomarkers; Blood Coagulation Factors; Dalteparin; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Half-Life; Humans; Male; Middle Aged; Peptide Fragments; Prothrombin; Stroke; Thrombophilia; Time Factors; Vitamin K; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Echocardiography; Europe; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Placebos; Risk Factors; Thromboembolism; Vitamin K

Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS.. The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers.. Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n = 30) of patients had decompensated liver disease, and 87.2% (n = 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n = 16 of 22) of patients were switched from low-molecular-weight heparin (n = 12) or vitamin K antagonist (n = 4) to DOAC after disease stabilization or improvement, 27.3% (n = 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n = 2 upper gastrointestinal bleeding, n = 1 lower gastrointestinal bleeding, n = 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years.. DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Austria; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Dabigatran; End Stage Liver Disease; Gastrointestinal Hemorrhage; Humans; Liver Neoplasms; Retrospective Studies; Severity of Illness Index; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Humans; International Normalized Ratio; Vitamin K

Since the introduction of direct oral anticoagulants (DOACs) for the treatment of nonvalvular atrial fibrillation (Afib), oral anticoagulants (OACs) prescription has evolved.. We aim first to explore the OACs prescription behaviour in Flanders from 2002 to 2019 before exploring the impact of switching patients from vitamin K antagonists (VKAs) to DOACs in terms of the burden caused by stroke as a complication of non-valvular Afib.. Data were obtained from INTEGO, a Flemish, general practice-based morbidity registration network. Comprised patients had at least one visit to their GP per year between 2002 and 2019 and a follow-up of at least 1 year after the diagnosis of Afib. Public prices were retrieved from the Belgian Centre for Pharmacotherapeutic Information (BCFI) and the National Institute for Health and Disability Insurance (RIZIV/ INAMI) sites. The number of Disability-Adjusted Life Years (DALYs) was based on the Global Burden of Disease (GBD) literature. The calculation of the Number Needed to Switch (NNSw) was the basis for conducting cost-utility analyses accounting for the global benefit in terms of the cost of prevented stroke/DALY and the cost of switching Flemish ≥ 65 years patients from VKAs to DOACs in two scenarios.. Increased DOAC use has been observed since 2012. The incremental cost effectiveness ratios (ICERs) yielded 553 to 824 €/DALY of prevented stroke.. In this registry-based study, we found a significant positive trend in OAC use in Flanders between 2002 and 2019. Switching to DOACs seems cost-effective compared to a threshold of 20000€/DALY.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Guidelines are discordant on the use of a vitamin K antagonist (VKA) after mitral valve repair (MVr) to reduce the risk of cerebral embolic events. We performed an observational study among patients who underwent a MVr, without perioperative atrial fibrillation, to determine the risk of cerebral ischemic and major bleeding events with or without VKA.. From 2004 to 2016, we included patients who underwent MVr, using a national administrative claims database. Those with preoperative atrial fibrillation and anticoagulant use were excluded. Patients were stratified based on the presence of a VKA. Inverse probability weighting with a Cox proportional hazard model was used.. After MVr, 754 patients were discharged on VKA and 1462 on no-VKA. We found no difference in the cumulative incidence for embolic stroke at 180 days (VKA: 2.21% vs no-VKA: 1.50%; hazard ratio, 1.35; P = .38). However, VKA patients had a significantly increased risk for any-cause major bleeding events at 180 days (VKA: 8.58% vs no-VKA: 4.21%; hazard ratio, 2.09; P < .001). VKA patients also had increased need for a pericardiocentesis/pericardial window at 30 days after discharge (VKA: 1.13% vs no-VKA: 0.37%; hazard ratio, 3.88; P = .025).. Our study suggests that VKA after MVr does not reduce the risk of cerebral embolic events but is associated with an increased risk of major bleeding events.

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Mitral Valve; Stroke; Vitamin K

The SAMe-TT

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Humans; International Normalized Ratio; Venous Thromboembolism; Vitamin K

GReek-AntiPlatElet Atrial Fibrillation registry is a multicenter, observational, noninterventional study of atrial fibrillation patients undergoing percutaneous coronary intervention. Primary endpoint included clinically significant bleeding rate at 12 months between different antithrombotic regimens prescribed at discharge; secondary endpoints included major adverse cardiovascular events and net adverse clinical events. A total of 647 patients were analyzed. Most (92.9%) were discharged on novel oral anticoagulants with only 7.1% receiving the vitamin K antagonist. A little over half of patients (50.4%) received triple antithrombotic therapy (TAT)-mostly (62.9%) for ≤1 month-whereas the rest (49.6%) received dual antithrombotic therapy (DAT). Clinically significant bleeding risk was similar between TAT and DAT [Hazard ratio (HR) = 1.08; 95% confidence interval (CI), 0.66-1.78], although among TAT-receiving patients, the risk was lower in those receiving TAT for ≤1 month (HR = 0.50; 95% CI, 0.25-0.99). Anticoagulant choice (novel oral anticoagulant vs. vitamin K antagonist) did not significantly affect bleeding rates ( P = 0.258). Age, heart failure, leukemia/myelodysplasia, and acute coronary syndrome were associated with increased bleeding rates. Risk of major adverse cardiovascular events and net adverse clinical events was similar between ΤAT and DAT (HR = 1.73; 95% CI, 0.95-3.18, P = 0.075 and HR = 1.39; 95% CI, 0.93-2.08, P = 0.106, respectively). In conclusion, clinically significant bleeding and ischemic rates were similar between DAT and TAT, although TAT >1 month was associated with higher bleeding risk.

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Greece; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Education, Continuing; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Rheumatic Heart Disease; Standard of Care; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Transcatheter Aortic Valve Replacement; Vitamin K

Connolly SJ, Karthikeyan G, Ntsekhe M, et al.

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Rheumatic Heart Disease; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

Thromboembolic events after catheter ablation of ventricular tachycardia (VT) can result in significant morbidity. Thromboembolic prophylaxis after catheter ablation can be achieved by the use of antiplatelet agents, vitamin K antagonists, or direct oral anticoagulants (DOACs). The relative safety and efficacy of these modes of prophylaxis are uncertain. We sought to compare the outcomes of patients who received warfarin or DOACs for thromboembolic prophylaxis after catheter ablation of VT.. Anticoagulation with DOACS was started after left ventricular VT ablation in a series of 42 consecutive patients with structural heart disease (67 ± 11 years, 3 women, ejection fraction 32 ± 14%). Duration of hospital stay, bleeding episodes, and thromboembolic events were compared to a historic consecutive group of patients (n = 38, 65 ± 13 years, 14 women, ejection fraction 36 ± 13%) in whom anticoagulation with a formerly described protocol of heparin and vitamin K antagonist was used after VT ablation procedures. Hospital stay was significantly shorter in the group where DOACs were used as compared to vitamin K antagonists (3.3 ± 1.8 vs. 5.0 ± 2.5 days postablation; p = 0.001) without an increase of bleeding or thromboembolic events.. Anticoagulation with DOACs is safe and shortens hospital stay in patients with structural heart disease undergoing left ventricular VT ablation procedures.

Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Hemorrhage; Humans; Tachycardia, Ventricular; Thromboembolism; Vitamin K; Warfarin

The use of direct oral anticoagulants (DOACs) is increasing in patients needing treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (SPAF). This is due to the net clinical benefit in comparison to vitamin K antagonists (VKAs). The rise in DOAC use is accompanied by a remarkable reduction in heparin and VKA prescriptions. However, this rapid change in anticoagulation patterns brought new challenges to patients, prescribers, laboratories, and emergency physicians. Patients have new liberties concerning nutritional habits and comedication and no longer need frequent monitoring or dose adjustments. Still, they have to comprehend that DOACs are potent anticoagulants that may cause or contribute to bleeding. Challenges for the prescriber include decision pathways for choosing the right anticoagulant and dosage for a specific patient and to change bridging practice in case of invasive procedures. Laboratory personnel are challenged by DOAC due to limited 24/7 availability of specific DOAC quantification tests and by the impact of DOAC on routine coagulation assays and thrombophilia tests. Challenges for the emergency physician result from the increasing age of DOAC anticoagulated patients, the difficulties to establish last intake of DOAC type and dosage, to interpret coagulation test results in emergency situations, and to make decisions for or against DOAC reversal strategies in acute bleeding or urgent surgery. In conclusion, although DOACs make long-term anticoagulation safer and more convenient for patients, DOACs pose challenge to all healthcare providers involved in anticoagulation decisions. The key to correct patient management and optimal outcome therefore lies in education.

Topics: Administration, Oral; Anticoagulants; Antidotes; Atrial Fibrillation; Hemorrhage; Heparin; Humans; Laboratories; Venous Thromboembolism; Vitamin K

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67-0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66-0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90-0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Sex Characteristics; Vitamin K

Oral anticoagulant therapy is the cornerstone of atrial fibrillation management to prevent stroke and systemic embolism. However, there is limited real-world information regarding stroke and systemic embolism prevention strategies in patients with atrial fibrillation. The aim of the ROTA study is to obtain the real-world data of anticoagulant treatment patterns in patients with atrial fibrillation.. The ROTA study is a prospective, multicenter, and observational study that included 2597 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January 2021 and May 2021.. The median age of the study population was 72 years (range: 22-98 years) and 57.4% were female. The median CHA2DS2-VASc and HAS-BLED scores were 4 (range: 0-9) and 1 (range: 0-6), respectively. Vitamin K antagonists and direct oral anticoagulants were used in 15.9% and 79.4% of patients, respectively. The mean time in therapeutic range was 52.9% for patients receiving vitamin K antagonists, and 76% of those patients had an inadequate time in therapeutic range with <70%. The most common prescribed direct oral anticoagulants were rivaroxaban (38.1%), apixaban (25.5%), and edoxaban (11.2%). The rate of overuse of vitamin K antagonists and direct oral anticoagulants was high (76.1%) in patients with low stroke risk, and more than one-fourth of patients on direct oral anticoagulant therapy were receiving a reduced dose of direct oral anticoagulants. Among patients who were on direct oral anticoagulant treatment, patients with apixaban treatment were older, had higher CHA2DS2-VASc and HAS-BLED scores, and had lower creatinine clearance than the patients receiving other direct oral anticoagulants.. The ROTA study provides important real-world information about anticoagulant treatment patterns in patients with atrial fibrillation.time in therapeutic range with <70%.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Humans; Male; Middle Aged; Prospective Studies; Pyridones; Rivaroxaban; Stroke; Vitamin K; Young Adult

Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).. We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)].. In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Humans; Phenprocoumon; Risk Factors; Stroke; Vitamin K

Limited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period.. The Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0-3, 4-6, and 7-12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled.. A 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30-59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40-0.77, P = 0.001) in the lower (0-1) CHA. Thromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Hungary; Insurance, Health; Middle Aged; Stroke; Thromboembolism; Vitamin K

Although widely used in clinical fields, real-world data on the role of warfarin and non-vitamin K oral anticoagulants (NOACs) for the secondary prevention of thromboembolic complications in ischemic stroke patients with nonvalvular atrial fibrillation (NVAF) are scarce.. This retrospective cohort study compared the effectiveness and safety of secondary prevention of NOAC and warfarin in ischemic stroke patients with NVAF.. From the Korean National Health Insurance Service Database, we included 16,762 oral anticoagulants-naive acute ischemic stroke patients with NVAF between July 2016 and June 2019. The main outcomes included ischemic stroke, systemic embolism, major bleeding, and all-cause of death.. In total, 1717 warfarin and 15,025 NOAC users were included in the analysis. After 1:8 propensity score matching, during the observation period, all types of NOACs had a significantly lower risk of ischemic stroke and systemic embolism than warfarin (edoxaban: adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.68-0.93, rivaroxaban: aHR, 0.82; 95% CI, 0.70-0.96, apixaban: aHR, 0.79; 95% CI, 0.69-0.91, and dabigatran: aHR, 0.82; 95% CI, 0.69-0.97). Edoxaban (aHR, 0.77; 95% CI, 0.62-0.96), apixaban (aHR, 0.73; 95% CI, 0.60-0.90), and dabigatran (aHR, 0.66; 95% CI, 0.51-0.86) had lower risks of major bleeding and all-cause of death.. All NOACs were more effective than warfarin in the secondary prevention of thromboembolic complications in ischemic stroke patients with NVAF. Except for rivaroxaban, most NOACs demonstrated a lower risk of major bleeding and all-cause of death than warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Ischemic Stroke; Retrospective Studies; Rivaroxaban; Secondary Prevention; Stroke; Thromboembolism; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs) are widely used for the treatment of venous thromboembolism (VTE) and for stroke prevention in atrial fibrillation (AF). However, evidence in obese and underweight patients is limited. We assessed the safety and effectiveness of DOACs and vitamin K antagonists (VKAs) in patients  ≥ 120 kg or ≤ 50 kg enrolled in an observational prospective cohort study, the START-Register.. Adult patients started on anticoagulant therapy were followed up for a median of 1.5 years (IQR 0.6-2.8). Primary efficacy outcome was the occurrence of VTE recurrence, stroke and systemic embolism. Primary safety outcome was major bleeding (MB).. 10,080 AF and VTE patients were enrolled between March 2011 and June 2021, 295 patients weighted  ≤ 50 kg and 82 patients ≥ 120 kg. Obese patients were significantly younger than underweight patients. Rates of thrombotic events were low and similar between DOACs and VKAs in underweight patients (1 event on DOACs therapy [0.9% 95% CI 0.11-5.39] and 2 on VKAs [1.1% 95% CI 0.01-47.68]) and in overweight patients (0 events on DOACs, 1 on VKAs [1.6%, 95% CI 0.11-5.79]. Two MB events occurred on DOACs (1.9%, 95% CI 0.38-6.00) and 3 on VKAs (1.6%, 95% CI 0.04-22.06) in the underweight group; 1 MB on DOACs (5.3% 95% CI 0.33-16.68) and 2 on VKAs (3.3%, 95% CI 0.02-130.77) in the overweight group.. DOACs seem to be effective and safe also for the treatment of patients with extreme body weights, both underweight and overweight. Further prospective studies are needed to support these findings.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Obesity; Overweight; Prospective Studies; Stroke; Thinness; Venous Thromboembolism; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Fibrinolytic Agents; Humans; Stroke; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and in recent years the pharmacological approach has been strongly implemented; in Italy, the prescription of the non-vitamin K oral anticoagulants (NOAC) was also extended to General Practitioners (GPs) since 2020. The aim of the present study was to investigate the GPs prescribing behaviour of NOACs. An observational study was performed by using the computerized medical record of 14 GPs in Sicily: patients affected by AF were selected and stratified according to the prescribed antithrombotic drugs. Patients were considered inadequately managed if antithrombotic treatment was not adherent to recent ESC guidelines. A total of 467 (2.7 %) patients were affected by AF, 276 (59.1 %) were treated with an oral anticoagulant (OAC) regardless the high stroke risk (OR 1.64; 95 %CI 0.74-3.62; p = 0.226). The NOAC users were 236 patients as follow: Rivaroxaban 33.5 %, Apixaban 33,1 %, Dabigatran 17,4 %, Edoxaban 16.1 %. In 7 patients an inappropriate NOAC treatment was observed. Among Vitamin-K antagonist users, 25.0 % were considered inappropriate. Patients not treated with OAC were 191, of them 81.7 % were at high stroke risk and did not receive any OAC despite the indication to treat. In addition, the probability to be not properly managed significantly increased in older and in patients with atherosclerosis. Conversely, patients with at least one reported cardiology counselling significantly reduced the likelihood to be not properly managed (OR 0.38, 95 %CI 0.25-0.58; p 0.01). Our results suggest the need to optimize the management of real-life AF patients by improving prescribing adherence to ESC guidelines.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; General Practice; Humans; Stroke; Vitamin K

Atrial fibrillation is the most prevalent persistent dysrhythmia, contributing to a significant social and economic burden. The main objective of this study was to evaluate the association between oral anticoagulant use and the incidence of stroke associated with atrial fibrillation, in mainland Portugal.. The number of episodes of inpatient care with a main diagnosis of stroke and an additional diagnosis of atrial fibrillation, occurring monthly between January 2012 and December 2018, in individuals aged 18 years or over, was extracted from the hospital morbidity database. The number of patients with an atrial fibrillation code documented in this database was used as a proxy for the prevalence of known atrial fibrillation. The number of anticoagulated patients was estimated from total medicine sales of vitamin K antagonists and novel oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) in mainland Portugal. Descriptive analyses were performed, and seasonal autoregressive integrated moving average (SARIMA) models were built using the R software.. The mean number of episodes of stroke per month was 522 (± 57). The number of anticoagulated patients increased gradually from 68 943 to 180 389 per month. The decreasing trend in the number of episodes has been observed since 2016, along with the increased use of new oral anticoagulants compared to vitamin K antagonists. The final model indicated that the increase in oral anticoagulation use between 2012 and 2018, in mainland Portugal, was associated with a decrease in the number of episodes of stroke associated with atrial fibrillation. It was estimated that the shift in the type of anticoagulation used, between 2016 and 2018, was associated with a reduction of 833 episodes of stroke in patients with atrial fibrillation (4.2%).. The use of oral anticoagulation was associated with a reduced incidence of stroke in patients with atrial fibrillation in mainland Portugal. This reduction was more relevant in the period between 2016 and 2018, and is probably related with the introduction of the novel oral anticoagulants.. Introdução: A fibrilhação auricular é a disritmia persistente mais prevalente, tendo um importante impacto social e económico. O objetivo principal deste estudo foi avaliar a associação entre a utilização de anticoagulantes orais e a incidência de acidente vascular cerebral associado a fibrilhação auricular, em Portugal continental. Métodos: A base de dados de morbilidade hospitalar foi utilizada para a contabilização dos episódios de internamento com um diagnóstico principal de acidente vascular cerebral e um diagnóstico adicional de fibrilhação auricular, ocorridos durante cada mês do período em análise (janeiro de 2012 a dezembro de 2018), em indivíduos com idade igual ou superior a 18 anos. O número de doentes com registo de fibrilhação auricular presentes nesta base de dados foi utilizado como um proxy da prevalência de fibrilhação auricular conhecida. O número de doentes anticoagulados foi estimado a partir das estatísticas das vendas de antagonistas da vitamina K e novos anticoagulantes orais (apixabano, dabigatrano, edoxabano e rivaroxabano) em Portugal continental. Foi realizada uma análise descritiva das variáveis, construindo-se depois modelos auto-regressivos integrados de médias móveis sazonais (seasonal autoregressive integrated moving average, SARIMA), com recurso ao software R. Resultados: Ocorreram, em média, 522 (± 57) episódios de acidente vascular cerebral por mês. Verificou-se um aumento gradual do número de doentes anticoagulados, passando de 68 943 para 180 389, por mês. A tendência decrescente no número de episódios verificou-se a partir de 2016, a par da maior utilização dos novos anticoagulantes orais, comparativamente aos antagonistas da vitamina K. O modelo final estimado indicou que o aumento do consumo de anticoagulação oral entre 2012 e 2018 em Portugal continental foi associado a um decréscimo do número de acidentes vasculares cerebrais associados a fibrilhação auricular. Estimou-se que, entre 2016 e 2018, a mudança no tipo de anticoagulação se associou a uma redução de 833 episódios de acidentes vascular cerebrais em doentes com fibrilhação auricular (4,2%). Conclusão: A anticoagulação oral associou-se à redução da incidência de acidente vascular cerebral em doentes com fibrilhação auricular, em Portugal continental. Esta redução foi mais relevante no período 2016 a 2018, em provável relação com a introdução dos novos anticoagulantes orais.

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Incidence; Portugal; Stroke; Vitamin K

An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs).. An externally validated model improves ICH risk stratification.. Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register.. In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets.. Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Registries; Renal Insufficiency, Chronic; Risk Factors; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Liver Cirrhosis; Neuroprotection; Vitamin K

To study the confidence of cardiologists in performing an electrical cardioversion in patients on oral anticoagulation (OA) with or without transoesophageal echocardiography (TOE).. Data about atrial fibrillation (AF) patients admitted to cardiology wards for elective cardioversion (ECV) were extrapolated from the BLITZ-AF study. Percentage of vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) and heparin prescription were analysed in relation to the use of TOE before ECV.. Overall rate of TOE was 33.7% (240/713); it was used before ECV in 124/313 (39.6%) of DOACs patients and in 96/372 (25.8%) of the patients on VKAs, showing a significant reduced resort to TOE in VKAs patients (p = 0.0001). Among non-valvular patients TOE was more frequently performed in males, at younger ages and in patients on heparin when compared to patients treated with OA. TOE was also more frequently performed in tertiary hospitals and in hospitals with cardiology wards and electrophysiology labs, when compared to hospital provided only with cardiology wards. At multivariable analysis there was a significant less recourse to TOE in patients on VKAs (OR 0.47; 95% CI: 0.33-0.67) and higher recourse in the heparin group (OR: 3.85; 95% CI:1.59-9.28) with respect to patients on DOACs; a higher recourse to TOE was observed also in tertiary hospitals (OR 4.25; 95% CI 2.69-6.69) and in hospitals with cardiology wards and electrophysiology (EP) labs (OR 1.87; 95% CI 1.23-2.82).. our study shows the reluctance in cardioverting patients on DOACs respect to VKAs without a previous TOE, despite adequate anticoagulant treatment.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Electric Countershock; Fibrinolytic Agents; Heparin; Humans; Male; Stroke; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Humans; Morbidity; Vitamin K

To assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE).. All children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models.. We included 405 patients. Median follow-up was 18.7 (9.3-49.4) months. The median TTR was 83.1 % (74.4 %-95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1-1.8]) and 2.3 % (CI95 % [0.9-3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %-99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2-8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6-11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5-15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9-32.0], p = 0.005) was the only risk factor for thrombotic events.. Overall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.

Topics: Anticoagulants; Atrial Fibrillation; Child; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; Prospective Studies; Risk Factors; Thrombosis; Vitamin K

An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure.. We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016. The different outcomes of patients with DOAC failure were compared, including recurrent ischemic stroke, major cardiovascular events, intracranial hemorrhage and subarachnoid hemorrhage, mortality, and net composite outcomes according to switching to different DOACs or vitamin K antagonist after index ischemic stroke. We identified 3759 patients with DOAC failure. A total of 84 patients experienced recurrent ischemic stroke after switching to different oral anticoagulants, with a total follow-up time of 14 years. Using the vitamin K antagonist group as a reference, switching to any of the 4 DOACs was associated with a 69% to 77% reduced risk of major cardiovascular events (adjusted hazard ratio [aHR], 0.25 [95% CI, 0.16-0.39] for apixaban, 0.23 [95% CI, 0.14-0.37] for dabigatran, 0.23 [95% CI, 0.09-0.60] for edoxaban, and 0.31 [95% CI, 0.21-0.45] for rivaroxaban), and a 69% to 83% reduced risk of net composite outcomes (aHR, 0.25 [95% CI, 0.18-0.35] for apixaban, 0.17 [95% CI, 0.11-0.25] for dabigatran, 0.31 [95% CI, 0.17-0.56] for edoxaban, and 0.31 [95% CI, 0.23-0.41] for rivaroxaban).. In Asian patients with DOAC failure, continuing DOACs after index stroke was associated with fewer undesirable outcomes than switching to a vitamin K antagonist. Alternative pharmacologic and nonpharmacologic strategies warrant investigation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Ischemic Stroke; Retrospective Studies; Rivaroxaban; Stroke; Subarachnoid Hemorrhage; Vitamin K; Warfarin

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhagic Stroke; Humans; Stroke; Vitamin K

The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF) has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5 years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion, in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.

Topics: Administration, Oral; Aftercare; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Octogenarians; Patient Discharge; Prognosis; Retrospective Studies; Stroke; Vitamin K

Left ventricular thrombi form due to the presence of Virchow's triad in patients with left ventricular systolic dysfunction. This complication increases the incidence of systemic embolization, hence anticoagulation is recommended to decrease this risk. Up to the present time, vitamin K antagonists are recommended by all societal guidelines for patients with left ventricular thrombi. Recently, several studies have investigated the role of different anticoagulants and yielded promising outcomes. This opinion article focuses on the evidence supporting vitamin K antagonists and direct oral anticoagulants in patients with left ventricular thrombi.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Thrombosis; Ventricular Dysfunction, Left; Vitamin K

To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.. Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.. The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78-88.

Topics: Aged, 80 and over; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Stroke; Vitamin K

Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low.. To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC.. Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models.. A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR ≤ 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3-17.0%) of the patients with a pre-switch TTR ≤ 45% became non-persistent to DOAC within 1 year, while 9.8% (95% CI 8.7-11.0%) did in those with a pre-switch TTR > 45%. In a multivariable model, a pre-switch TTR ≤ 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR.. NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

The aim of the study was to compare the real-world effectiveness and safety in atrial fibrillation (AF) patients treated with edoxaban versus other oral anticoagulants (OACs) (apixaban, dabigatran, rivaroxaban, and vitamin K antagonists [VKA]) in Germany.. Using a representative database of 3.5 million statutory health-insured lives in Germany, a retrospective cohort study was conducted to examine ischemic stroke (IS) or systemic embolism (SE) and major bleeding in AF patients initiating anticoagulant therapy from January 2014 through June 2017. Inverse probability of treatment weighting using propensity score was applied for baseline covariate adjustment. Cox proportional hazards models were used to estimate the adjusted risk (hazard ratio [HR]) of each outcome comparing edoxaban versus other OACs. Among 21,038 patients treated with OACs, 1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA patients were included. The adjusted combined risks of IS or SE were lower (p < 0.05) for each edoxaban pairwise comparison with other OACs (HR: 0.83 vs. apixaban, 0.60 vs. dabigatran, 0.72 vs. rivaroxaban, 0.64 vs. VKA). Edoxaban favored lower risks of major bleeding compared with rivaroxaban (HR: 0.74) and VKA (HR: 0.47). No differences in the risk of major bleeding were found between edoxaban and apixaban (p = 0.33), and between edoxaban and dabigatran (p = 0.06).. Edoxaban was associated with better effectiveness compared with other OACs in AF patients from Germany. Edoxaban also demonstrated a favorable safety profile.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Humans; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Thiazoles; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Vitamin K; Warfarin

Background Clinical evidence on the safety and effectiveness of using direct oral anticoagulants (DOACs) in patients with atrial fibrillation after transcatheter aortic valve replacement (TAVR) remains limited. The aim of this study was to investigate the trends and outcomes of using DOACs in patients with TAVR and atrial fibrillation. Methods and Results Data from the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry was used to identify patients who underwent successful TAVR with preexisting or incident atrial fibrillation who were discharged on oral anticoagulation between January 2013 and May 2018. Patients with a mechanical valve, valve-in-valve procedure, or prior stroke within a year were excluded. The adjusted primary outcome was 1-year stroke events. The adjusted secondary outcomes included bleeding, intracranial hemorrhage, and death. A total of 21 131 patients were included in the study (13 004 TAVR patients were discharged on a vitamin K antagonist and 8127 were discharged on DOACs.) The use of DOACs increased 5.5-fold from 2013 to 2018. The 1-year incidence of stroke was comparable between DOAC-treated patients and vitamin K antagonist-treated patients (2.51% versus 2.37%; hazard ratio [HR], 1.00; 95% CI, 0.81-1.23) whereas DOAC-treated patients had lower 1-year incidence of any bleeding (11.9% versus 15.0%; HR, 0.81; 95% CI, 0.75-0.89), intracranial hemorrhage (0.33% versus 0.59%; HR, 0.54; 95% CI, 0.33-0.87), and death (15.8% versus 18.2%; HR, 0.92; 95% CI, 0.85-1.00). Conclusions In patients with TAVR and atrial fibrillation, DOAC use, when compared with vitamin K antagonists, was associated with comparable stroke risk and significantly lower risks of bleeding, intracranial hemorrhage, and death at 1 year.

Topics: Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Registries; Risk Factors; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; United States; Vitamin K

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: 'Are NOACs as safe and efficient as vitamin K antagonist regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?' Altogether more than 324 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The RIVER and ENAVLE trials showed non-inferiority of rivaroxaban (regarding mean time free from composite of death, major cardiovascular events or major bleeding at 12 months) and edoxaban (composite of death, clinical thromboembolic events or asymptomatic intracardiac thrombosis; and major bleeding) when compared with vitamin K antagonist. These studies include a low number of patients within 3 months of index surgery and overall low statistical power regarding this particular subgroup of patients. Data derived from lower evidence studies are compatible with the aforementioned findings. The available evidence suggests that non-vitamin K antagonist anticoagulants are as safe and as efficient as vitamin K antagonist regarding thromboembolic prophylaxis and bleeding event rates in patients with surgical bioprosthesis and atrial fibrillation within 3 months of bioprosthesis implantation. However, this evidence is derived from a limited number of studies with important methodological limitations. Expanding non-vitamin K antagonist anticoagulant recommendation to the early postoperative period warrants more confirmatory research.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Thromboembolism; Vitamin K

Despite patients with cancer having a higher incidence of atrial fibrillation (AF), little is known about the predictors of outcomes in this population. This study aimed to assess the incidence and predictors of bleeding in patients with AF and cancer. The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 (1,137 with cancer). Competing risk analysis were used to evaluate the association of cancer and bleeding. Discrimination and calibration of bleeding risk scores were assessed by the concordance statistic and the Brier score, respectively. During a median follow-up of 4.9 years, the incidence of bleeding in patients with cancer was 13.2 per 100 patients/year. After multivariate adjustment, a significant association between cancer and bleeding was detected (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.07 to 1.30, p = 0.001), specifically in patients with active cancer or previous radiotherapy. Early age, male gender, diabetes, and anticoagulation were independent predictors of bleeding. However, only anticoagulation with vitamin K antagonist (sHR 1.36, 95% CI 1.03 to 1.78, p = 0.026), not with direct oral anticoagulants (sHR 1.25, 95% CI 0.84 to 1.85, p = 0.270), was associated with bleeding. Discrimination and calibration of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, and Drugs/alcohol concomitantly (HAS-BLED), AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), and Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age ≥75 years), Reduced platelet count or function, Rebleeding risk, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR

Topics: Aged; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Hypertension; Incidence; Male; Neoplasms; Risk Assessment; Risk Factors; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Rate; Hemorrhage; Humans; Stroke; Vitamin K; Warfarin

Given that vitamin K-dependent anticoagulants (VKAs) will continue to be the primary anticoagulant in Africa for a long time, understanding the quality of anticoagulation services in the continent is vital for optimising the intended benefits. Notably, a few small studies have assessed the quality of anticoagulation in sub-Saharan Africa (SSA) countries. This study will describe the current VKA use and anticoagulation control among patients in selected SSA countries.. We plan to review the 2019 anticoagulation data of a cohort of 800 random patients from 19 selected clinics in Botswana, the Democratic Republic of Congo, Ethiopia, Gambia, Ghana, Mozambique, Nigeria, Tanzania and South Africa. We expect at least one participating site to enrol 100 participants in each country. Eligible participants will be those on VKAs for at least 3 months and with at least four international normalised ratio (INR) results. We will document the indications, type and duration of VKA use, sociodemographic factors, coexisting medical conditions, concurrent use of drugs that interact with warfarin and alcohol and tobacco products. The level of anticoagulation control will be determined by calculating the time-in-therapeutic range (TTR) using the Rosendaal and the Percent of INR in TTR methods. A TTR of less than 65% will define a suboptimal anticoagulation control.. This study was approved by the Ministry of Health and Wellness Ethics Committee (HPDME13/8/1) in Botswana and local research ethics committees or institutional review boards of all participating sites. As the study collects data from existing records, sites applied for waivers of consent. We will disseminate research findings through peer-reviewed scientific publications.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; International Normalized Ratio; Retrospective Studies; South Africa; Vitamin K

In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes.. EVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months.. The study included 585 patients (median age [range] 82.3 [43.6-96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA. In the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Stroke; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Pyridines; Thiazoles; Transcatheter Aortic Valve Replacement; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Pyridines; Thiazoles; Transcatheter Aortic Valve Replacement; Vitamin K

Background Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent-onset AF enrolled in a large global registry. Methods and Results Eligible participants were recruited into GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation), a prospective observational cohort study from 2014 to 2016 in 4 international regions: North America, Europe, Asia, and Latin America. Cumulative incidence functions were generated for direct OACs (DOAC), vitamin K antagonists, and antiplatelet drugs considering competing risks, stratified by region and type of site. Time-to-treatment initiation after AF diagnosis was analyzed with Fine-Gray subdistribution hazard models. A total of 21 237 patients eligible for analysis were identified. By 30 days after AF diagnosis, 40%, 16%, and 8.6% of patients had DOAC, vitamin K antagonists, and antiplatelet drugs initiated, respectively. Earlier initiation of DOACs was observed in Europe, with Asia and Latin America having lower hazard rates of DOAC time-to-treatment initiation than Europe (hazard ratio [HR], 0.66; 95% CI, 0.62-0.70 and HR, 0.79; 95% CI, 0.73-0.85, respectively). DOAC initiation was highest in community hospitals, vitamin K antagonists in outpatient health care centers/anticoagulation clinics, and antiplatelet drugs in primary care clinics. Conclusions Important geographic variability exists with the use of OACs for patients with AF. Differences in the time-to-treatment initiation of OAC by type of site suggests suboptimal implementation of guideline recommendations and could result in less benefit and more harm. Optimizing OAC use for patients with AF may improve outcomes and reduce health care costs. Registration URL: http://www.clinicaltrials.gov; Unique identifiers: NCT01468701, NCT01671007.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Factors; Stroke; Vitamin K

Prospectively collected, routine clinical practice-based data on antithrombotic therapy in non-valvular atrial fibrillation (AF) patients are important for assessing real-world comparative outcomes. The objective was to compare the safety and effectiveness of dabigatran versus vitamin K antagonists (VKAs) in patients with newly diagnosed AF.. GLORIA-AF is a large, prospective, global registry program. Consecutive patients with newly diagnosed AF and CHA. Dabigatran was associated with a 39% reduced risk of major bleeding and 22% reduced risk for all-cause death compared with VKA. Stroke and myocardial infarction risks were similar, confirming a more favorable benefit-risk profile for dabigatran compared with VKA in clinical practice. Clinical trial registration https://www.. gov . NCT01468701, NCT01671007.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Prospective Studies; Registries; Stroke; Vitamin K

EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study in patients with pulmonary hypertension treated with riociguat. Patients were followed for 1-4 years, and the primary outcomes were adverse events (AEs) and serious AEs (SAEs), including embolic/thrombotic and hemorrhagic events. Here we report data on patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving a vitamin K antagonist (VKA; n = 683) or a non-vitamin K antagonist oral anticoagulant (NOAC; n = 198) at baseline. AEs and SAEs were reported in 438 patients (64.1%) and 257 patients (37.6%), respectively, in the VKA group, and in 135 patients (68.2%) and 74 patients (37.4%) in the NOAC group. Exposure-adjusted hemorrhagic event rates were similar in the two groups, while exposure-adjusted embolic and/or thrombotic event rates were higher in the NOAC group, although the numbers of events were small. Further studies are required to determine the long-term effects of anticoagulation strategies in CTEPH.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Hemorrhage; Humans; Hypertension, Pulmonary; Prospective Studies; Vitamin K

Rheumatic valve disease is present in 0.4 % of the word population, mainly in lowincome countries. Rheumatic mitral stenosis affects more women and between 40 to 75 % of patients may have atrial fibrillation (AF), more frequently in upper-middle income countries. This rhythm disturbance is due to increased atrial pressure, chronic inflammation, fibrosis, and left atrial enlargement. There is also an increase in the prevalence of AF with age in patients with mitral stenosis. The risk of stroke is 4 % per year. Success rates for cardioversion, Cox-Maze procedure, and catheter ablation are low. Therefore, anticoagulation with vitamin K antagonist is mandatory for Evaluated Heart valves, Rheumatic or Artificial (EHRA) classification type 1. However, this anticoagulation is used by less than 80 % of those eligible and less than 30 % have the international normalized ratio in the therapeutic range. The safety and efficacy of using rivaroxaban, a direct factor Xa inhibitor anticoagulant, were demonstrated in the RIVER trial with a sample of 1005 patients with AF and bioprosthetic mitral valve. The indication for valve replacement, that is, if severe mitral stenosis or severe mitral regurgitation, was not specified. A randomized, open-label study (DAVID-MS) is underway to compare the effectiveness and safety of dabigatran and warfarin therapy for stroke prevention in patients with AF and moderate or severe mitral stenosis. Thus, the applicability of the use of direct anticoagulants in patients with AF and mitral stenosis and also in those undergoing mitral bioprostheses surgery will be the subject of further studies. The findings may explain if specific atrial changes of mitral stenosis even after the valve replacement will influence thromboembolic events with direct anticoagulants.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Humans; Mitral Valve Stenosis; Rivaroxaban; Stroke; Vitamin K; Warfarin

This study aimed to determine the results of INR monitoring in patients on vitamin K antagonists (VKAs) and the time in therapeutic range (TTR) in 'real-world' settings.. Retrospective analysis of 836,857 INR measurements performed in adults from February 2010 to August 2015 in two districts in the French Brittany region.. Of the 836,857 INR measurements, 94.9% were ordered by general practitioners and 2.0% by cardiologists. The number of tests increased by 10-year age categories up to the age-group of 80-90 years. The number of INR measurements increased from 169,636 in 2011 to 176,184 in 2012, but then decreased slightly to 162,597 in 2013 and 164,427 in 2014. Mean coefficient of variation of INR was 19.0%, and mean TTR was 29.0%. TTR was higher in women than in men (31% vs. 18%), in older than in younger patients (19.1% at 40 years and 38.6% at 100 years) and in patients with arrhythmias than in those with deep vein thrombosis/pulmonary embolism (44.4% versus 19.4%) (p < 10. VKAs are still frequently prescribed in this era of direct oral anticoagulants. The low TTR cannot be explained by inadequate INR monitoring.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Data Analysis; Female; Fibrinolytic Agents; Humans; International Normalized Ratio; Male; Retrospective Studies; Vitamin K

Anticoagulant treatment increases the risk of intracerebral hemorrhage (ICH), but whether the treatment, more specifically non-vitamin K oral anticoagulants (NOACs), increases the risk of cerebral microbleeds (CMBs) remains uncertain. We performed this study to investigate the development of new CMBs due to NOACs or warfarin treatment in patients with atrial fibrillation (AF).We prospectively recruited AF patients before anticoagulation from June 2016 to June 2018. We performed susceptibility-weighted imaging (SWI) examinations on all enrolled AF patients and re-examined SWI 1 year later. We compared demographic features and new CMBs between the NOACs group and the warfarin group. Univariate analysis of clinical factors was performed according to the development of new CMBs; and age, a HAS-B(L)ED score, warfarin use, and the presence of baseline CMBs were then selected for inclusion in the multivariate logistic regression model.A total of 72 AF patients were recruited, 29 of whom were assigned to the NOACs group and 43 to the warfarin group. Finally, 1 patient in the NOACs group (3.4%) and 9 patients (20.9%) in the warfarin group developed new CMBs after 1 year follow-up (P = .08). Univariate analysis showed that age, a HAS-B(L)ED score ≥4, the presence of baseline CMBs were associated with the development of new CMBs (P < .05). And multivariate regression analysis showed baseline CMBs (P = .03, odds ratio = 6.37, 95% confidence interval 1.15-35.36) was independently related to the increase in new CMBs.AF patients treated with NOACs may have a decreased trend in the development of new CMBs compared with those treated with warfarin. Baseline CMBs increased the frequency of new CMBs during anticoagulant treatment. The development of new CMBs in AF patients with anticoagulation requires further longitudinal studies with longer follow-up in larger samples.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Follow-Up Studies; Humans; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Mitral Valve Stenosis; Pilot Projects; Stroke; Thromboembolism; Vitamin K

Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered.. From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment.. A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0-19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes.. The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Retrospective Studies; Sex Factors; Vitamin K; Warfarin

Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be preferred over vitamin K antagonists (VKA) in this indication. This recommendation applies also to patients with VHF and concomitant chronic kidney disease (CKD). Real World Evidence (RWE), i. e., structured data from clinical practice, extends and confirms the clinical evidence generated in more formalized clinical trials with NOAC and VKA. In addition, RWE in respect to the indication showed that the superiority of NOAC versus the VKA warfarin can also be extrapolated to phenprocoumon, the commonly used VKA in Germany. Furthermore, data include evidence that the typical progression of CKD appears to be less pronounced in individuals treated with NOAC compared to those treated with VKA.. Die momentanen Leitlinien empfehlen Nicht-Vitamin-K-abhängige orale Antikoagulanzien (NOAK) als Therapiestandard für die Schlaganfallprophylaxe bei Patienten mit Vorhofflimmern (VHF) und sind daher den Vitamin-K-Antagonisten (VKA) vorzuziehen. Diese Empfehlung gilt auch für Patienten mit VHF und chronischer nicht dialysepflichtiger Niereninsuffizienz. Sogenannte Real-World-Evidenz (RWE), also Daten aus der klinischen Praxis, erweitert und bestätigt die zugrunde liegende klinische Evidenz, die in den stärker formalisierten klinischen Prüfungen mit NOAK und VKA, hier ausschließlich Warfarin, gewonnen wurde. Darüber hinaus zeigte die RWE, dass die Überlegenheit der NOAK gegenüber dem VKA Warfarin auch für Phenprocoumon gilt, dem in Deutschland gebräuchlichsten VKA. Auch fanden sich Hinweise, dass bei Patienten mit chronischen Nierenerkrankungen das Fortschreiten der Nierenfunktionsstörung unter Behandlung mit NOAK geringer ausfallen kann als unter VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Renal Insufficiency, Chronic; Stroke; Vitamin K; Warfarin

Direct-acting oral anticoagulants (DOACs) were developed as an alternative to warfarin to treat and prevent thromboembolism, including stroke prevention in non-valvular atrial fibrillation patients. The COVID-19 pandemic could increase the risk of stroke and/or the risk of bleeding in patients due to nonadherence or sub/supra-optimal dosing.. To investigate DOAC prescription trends in England's community settings during the complete first wave of COVID-19 pandemic.. Descriptive and interrupted time series (ITS) analyses were conducted to examine the prescription patterns of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin for primary care patients in the English Prescribing Dataset from January 2019 to February 2021, with March 2020 as the cut-off point.. A 19% increase in mean DOAC's accompanied with 20% warfarin prescriptions decline was observed. ITS modelling showed an increase in DOAC prescription volume in March 2020 (+7 million items,

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; COVID-19; Dabigatran; England; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Interrupted Time Series Analysis; Pandemics; Prescriptions; Pyridones; Rivaroxaban; Stroke; Vitamin K; Warfarin

Balancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging.. To examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF.. Four hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1-2 (2-3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22-2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45-0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status.. Oral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Female; Hemorrhage; Humans; Liver Diseases; Male; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Vitamin K

(1) Background: Evaluation and improvement of the management of patients with atrial fibrillation in treatment with oral anticoagulants from primary health care. (2) Methods: prospective quasi-experimental study, conducted on 385 patients assisted with Atrial Fibrillation (AF) at the Las Fuentes Norte Health Center, before and after the implementation of actions to improve oral anticoagulants management from October 2015 to July 2017. (3) Results: The ACO-ZAR I study revealed that the population with AF presents a global prevalence of 1.7%, an indication of oral anticoagulants of 92.1%, undertreatment of 24%, suboptimal control of vitamin K antagonists of 43%, use of antiaggregant as primary prevention of 13.42%, and primary health care monitoring of 34%. The implementation of activities aimed at improving the management of oral anticoagulants in the ACO-ZAR II study achieves a reduction in undertreatment up to 16%, in the use of antiaggregant up to 9%, and in suboptimal control up to 30%, as well as an increase in control from primary health care up to 69.2% and of the penetrance of direct oral anticoagulants up to 28%. (4) Conclusions: In conclusion, the application of activities aimed at optimizing the management of oral anticoagulants in health center patients allowed the improvement of risk assessment and registration, undertreatment, use of antiaggregant, suboptimal control of vitamin K antagonists, control by primary health care center, and the penetrance of direct oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Primary Health Care; Prospective Studies; Stroke; Vitamin K

This retrospective observational study was conducted from 2010 to 2019 in National Center of Cardiovascular Diseases of China. We included patients with VT confirmed by imaging. The primary outcome was the rate of thrombus resolution. Hazard ratio (HR) was calculated with or without adjustment for covariates using Cox proportional hazards regression models.. 463 patients were included. 43.0% received VKAs, 16.6% received NOACs, and 40.4% received APT. Over a median of 468 days' follow-up, NOACs group was more likely to have the thrombus resolved within 12 months' follow-up than VKAs (HR 2.28, 95% CI 1.57 to 3.31) or APT (HR 2.92, 95% CI 1.97 to 4.33). After adjustment for baseline variables, the significance remained in the comparison of NOACs versus VKAs (HR 2.13, 95% CI 1.41 to 3.22) as well as NOACs versus APT (HR 2.55, 95% CI 1.53 to 4.27). No significant differences were identified in bleeding rate, thromboembolism rate, or all-cause death in 12 months' follow-up.. Our findings showed that patients who were male, diagnosed with MI with or without ventricular aneurysm, or diagnosed with coronary artery diseases medical history had a risk of thrombus unresolved. Patients with NOACs had a higher resolution and a similar safety profile comparing VKAs or APT, which persisted after adjusting for other factors. Large randomized controlled trials are required urgently. This trial is registered with NCT05006677.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Risk Factors; Thrombosis; Vitamin K

Efficacy and safety of vitamin K antagonists (VKAs) among atrial fibrillation (AF) patients are enhanced when the International Normalised Ratio (INR) is 2.0-3.0. Anticoagulation control among older patients is perceived to be lower and contributes to poorer initiation and uptake.. To examine the quality of INR control, adverse clinical outcomes, and factors associated with bleeding in older AF patients (≥80 years).. Anticoagulation control assessed by time in therapeutic range (TTR) (Rosendaal method) and percentage INRs in range (PINRR). Among the 205 patients aged ≥80 years, 58.5% were female, with mean (SD) CHA. Suboptimal (TTR and PINRR <70%) anticoagulation control was evident in all patients. Risk of bleeding increased, but there was no difference in thromboembolic events and all-cause mortality in those aged ≥80 years. Improving TTR to ≥70% and enhancing anticoagulation monitoring of VKA use remain a clinical priority to prevent bleeding complications, particularly among those aged 80 years and above.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Vitamin K

Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events.. A multicentre North American cohort study was conducted on patients with CHD who received VKAs for sustained atrial arrhythmia or Fontan palliation. TTR was calculated using the Rosendaal linear interpolation method. Generalized estimating equations were used to explore factors associated with time outside the therapeutic range.. A total of 567 patients, aged 33 ± 17 years, 56% female, received VKAs for 11.5 ± 8.4 years for atrial arrhythmias (63.0%) or Fontan palliation (58.0%). CHD was simple, moderate, and complex in 10.8%, 20.3%, and 69.0%, respectively. Site investigators perceived good control over international normalized ratio (INR) levels in most patients (75.3%), with no or minor compliance or adherence issues (85.6%). The mean TTR was 41.9% (95% confidence interval [CI], 39.0%-44.8%). Forty-seven (8.3%) and 34 (6.0%) patients had thromboembolic and bleeding events, respectively. Thromboembolic events were associated with a higher proportion of time below the therapeutic range (31.3% vs 19.1%, P = 0.003) and bleeding complications with a higher proportion of time above the therapeutic range (32.5% vs 19.5%, P = 0.006).. Patients with CHD who receive VKAs spend < 42% of their time with INR levels in the therapeutic range, with repercussions regarding thromboembolic and bleeding complications.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Fibrinolytic Agents; Heart Defects, Congenital; Hemorrhage; Humans; International Normalized Ratio; Male; Thromboembolism; Vitamin K

Therapeutic anticoagulation with either a vitamin K antagonist (VKA) or direct anticoagulant (DOAC) is often newly prescribed to patients undergoing lower extremity bypass (LEB) to aid in graft patency when risk factors for thrombosis are present or to treat postoperative venous thromboembolism or atrial fibrillation. There is a gap in knowledge as to how DOAC usage impacts postoperative outcomes compared with the standard-of-care VKAs.. To determine temporal trends in DOAC prescription after infrainguinal LEB, impact on length of stay (LOS), and associated bleeding and thrombotic complications, patients undergoing elective LEB were identified from the Vascular Quality Initiative between January 2013 and May 2019. Postoperative bleeding, LOS, and graft occlusion for patients receiving VKA compared with DOAC were evaluated.. A total of 24,459 LEBs were performed during the study period. Among 2,656 patients newly prescribed an anticoagulant, 78.0% (n = 2,072) received VKA and 22.0% (n = 584) received a DOAC, with DOAC use increasing throughout the study period. There was no significant difference in postoperative bleeding (VKA 2.3%, DOAC 1.7%, p = 0.413) or graft occlusion (VKA 1.2%, DOAC 1.4%, p = 0.762) between the anticoagulant classes. LOS was shorter in the DOAC group than in the VKA group (5.7 vs 6.8 days; p < 0.001).. This analysis demonstrates that DOAC use is increasing with time in Vascular Quality Initiative centers. DOACs are a safe and comparable alternative to VKAs in the postoperative setting with similar rates of bleeding complications and early graft patency and are associated with a reduced postoperative LOS.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Lower Extremity; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Lower Extremity; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Vitamin K

Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting.. The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up.. The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Stents; Vitamin K; Warfarin

To assess baseline characteristics and antithrombotic treatment (ATT) prescription patterns in patients enrolled in the third phase of the GLORIA-AF Registry Program, evaluate predictors of treatment prescription, and compare results with phase II.. GLORIA-AF is a large, global, prospective registry program, enrolling patients with newly diagnosed nonvalvular atrial fibrillation (AF) at risk of stroke. Patients receiving dabigatran were followed for two years in phase II, and all patients were followed for 3 years in phase III. Phase II started when dabigatran became available; phase III started when the characteristics of patients receiving dabigatran became roughly comparable with those receiving vitamin K antagonists (VKAs).. Between 2014 and 2016, 21,241 patients were enrolled in phase III. In total, 82% of patients were prescribed oral anticoagulation ([OAC]; 59.5% novel/nonvitamin K oral anticoagulants [NOACs], 22.7% VKAs). A further 11% of patients were prescribed antiplatelets without OAC and 7% were prescribed no ATT. A high stroke risk was the main driver of OAC prescription. Factors associated with prescription of VKA over NOAC included type of site, region, physician specialty, and impaired kidney function.. Over the past few years, data from phase III of GLORIA-AF show that OACs have become the standard treatment option, with most newly diagnosed AF patients prescribed a NOAC. However, in some regions a remarkable proportion of patients remain undertreated. In comparison with phase II, more patients received NOACs in phase III while the prescription of VKA decreased. VKAs were preferred over NOACs in patients with impaired kidney function.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Fibrinolytic Agents; Humans; Registries; Stroke; Vitamin K

Atrial fibrillation (AF) may be a pre-existing disease before cancer diagnosis, may be a direct effect of the neoplasm or, more often, appears as a post-surgical complication, especially after thoracic surgery. AF may also develop as a consequence of chemotherapy or radiotherapy. The management of the anticoagulation in cancer patients with AF is challenging, and data on these patients are lacking. The use of vitamin K antagonists (VKAs) may be problematic because of the unpredictable therapeutic response and high bleeding risk in patients with active cancer who are undergoing chemotherapy and who may experience thrombocytopenia and/or changes in renal or hepatic function. Low molecular weight heparins and direct oral anticoagulants (DOACs) could be preferred. However, the possible pharmacological interactions of DOACs with anti-cancer and anti-arrhythmic drugs and the bleeding risks in thrombocytopenic patients should be considered. Based on these considerations, a careful evaluation of the antithrombotic strategy with the best efficacy/safety ratio is always needed in cancer patients and anticoagulation for AF should be tailored individually. An ongoing consultation of oncologists/hematologists with cardiologists and coagulation experts in a multidisciplinary approach, with a periodic re-assessment of the benefits of anticoagulation with changes in cancer status/advancement and treatment plans is needed.

Topics: Administration, Oral; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Stroke; Vitamin K

To explore the predictive value of ABC bleeding score and SAMe-TT2R2 score on the risk of bleeding in patients with nonvalvular atrial fibrillation (NVAF) complicated with coronary heart disease (CHD) after anticoagulation.. 149 patients with NVAF complicated with CHD were followed up in our hospital for one year. The bleeding events during the follow-up period were observed, the ABC bleeding score and SAMe-TT2R2 score were calculated, the predictive value of the two scoring methods for the main bleeding risk was analyzed by the ROC curve, and the AUC area under the ROC curve of the two scoring methods was compared by the Delong test.. There were 32 bleeding events during the follow-up period. The AUC of ABC bleeding score and SAMe-TT2R2 score were 0.775 (. Both the ABC bleeding score and SAMe-TT2R2 score can predict the risk of bleeding after anticoagulation in patients with NVAF and CHD. The critical value of the SAMe-TT2R2 score for predicting bleeding events in patients with NVAF and CHD may need to be increased to 4 or 5, and the prediction ability of ABC bleeding score is significantly better than that of the SAMe-TT2R2 score.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Disease; Hemorrhage; Humans; Predictive Value of Tests; Stroke; Vitamin K

Circulating uncarboxylated matrix Gla protein (ucMGP) is possibly related to coronary arterial calcification (CAC) in cardiovascular disease (CVD) patients.. We aimed to evaluate the relationships between circulating ucMGP, CVD pathology and CAC and its interplay with CVD risk factors.. ucMGP was measured in 99 CVD-patients. CAC score was determined by multislice computed tomography. Circulating ucMGP, uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) were assayed by ELISA kits. Vitamin-K status was evaluated by ucOC/cOC ratio.. A tendency for decreased ucMGP was observed for CAC. Circulating ucMGP may reflect certain stages of CVD and CAC. Future studies are needed to clarify its role as potential biomarker.

Topics: Anticoagulants; Atrial Fibrillation; Biomarkers; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Heart Failure; Humans; Matrix Gla Protein; Osteocalcin; Stroke Volume; Vitamin K; Vitamins

Vitamin K antagonists (VKAs) are still in use for oral anticoagulation, but not all indications allow their replacement by direct oral anticoagulants. Although formal dose reduction is not required in patients with impaired kidney function, case reports indicate that acute kidney injury (AKI) might be associated with derailment of VKA therapy.. The study retrospectively collected patients from a tertiary nephrology care centre who experienced AKI while being treated with VKA. In these individuals, the international normalized ratio (INR) as a measure of anticoagulant effect during renal failure was compared with a reference time point with stable kidney function.. A total of 100 patients with AKI and ongoing VKA therapy met the inclusion criteria. The majority (76%) of patients had AKI with CKD. Volume depletion (n = 43), septic renal failure (n = 22), decompensated heart failure (n = 18) and toxic renal damage (n = 11) were the most important causes of AKI. The average INR values at the time of AKI were higher than at the reference time point [median 3.17 (range 1.10-13.0) versus 2.24 (1.07-5.17); P < 0.0001]. Fifty-four patients had INR values above the recommended therapeutic range for their indication at the time point of AKI. Bleeding complications occurred in 24 patients during AKI and the VKA dose had to be reduced in 55. Women, patients with low body mass index and patients with diabetes were predisposed to overanticoagulation during AKI.. The effect of AKI on anticoagulation by VKA has not been systematically described. This risk should be considered in patients at high risk for AKI.

Topics: Acute Kidney Injury; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; International Normalized Ratio; Male; Retrospective Studies; Vitamin K

In the absence of robust evidence to guide clinical decision-making, the optimal approach to prevent stroke and systemic embolism in haemodialysis (HD) patients with atrial fibrillation (AF) remains moot. In this position paper, studies on oral anticoagulation (OAC) in HD patients with AF are highlighted, followed by an evidence-based conclusion, a critical analysis to identify sources of bias and practical opinion-based suggestions on how to manage anticoagulation in this specific population. It remains unclear whether AF is a true risk factor for embolic stroke in HD. The currently employed cut-off values for the CHA2DS2-VASc score do not adequately discriminate dialysis patients deriving a net benefit from those suffering a net harm from OAC. Anticoagulation initiation should probably be more restrictive than currently advocated by official guidelines. Recent evidence reveals that the superior benefit-risk profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) observed in the general population and in moderate chronic kidney disease can be extended to the HD population. VKA may be especially harmful in dialysis patients and should therefore be avoided, in particular in patients with a high bleeding risk and labile international normalized ratio. Dose-finding studies of DOACs suggest that rivaroxaban 10 mg daily and apixaban 2.5 mg twice daily are appropriate choices in dialysis patients. Combined treatment with oral anticoagulants and antiplatelet agents should be reserved for strong indications and limited in time. Left atrial appendage occlusion is a potential attractive solution to reduce the risk of stroke without increasing bleeding propensity, but it has not been properly studied in dialysis patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Renal Dialysis; Risk Factors; Rivaroxaban; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Stroke; Surgeons; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Stroke; Vitamin K

The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19.. This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants.. Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; COVID-19; Fibrinolytic Agents; Humans; Respiratory Distress Syndrome; Retrospective Studies; Vitamin K

Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) <65%] in a 'real world' national cohort of AF patients.. The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain. At inclusion, all patients naïve for oral anticoagulation were started with VKAs for the first time. For the analysis, the first month of anticoagulation and those patients with <3 INR determinations were disregarded. Patients were followed up during 1 year. A total of 870 patients (53.9% male, the mean age of 73.6 ± 9.2 years, mean CHA2DS2-VASc and HAS-BLED of 3.3 ± 1.5 and 1.4 ± 0.9, respectively) were included in the full analysis set. In overall, 7889 INR determinations were available. At 1-year, the mean TTR was 63.1 ± 22.1% and 49.2% patients had a TTR < 65%. Multivariate Cox regression analysis showed that coronary artery disease [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.14-2.87; P = 0.012] and amiodarone use (OR 1.54, 95% CI 1.01-2.34; P = 0.046) were independently associated with poor quality of anticoagulation (TTR <65%).. This study demonstrated that the quality of anticoagulation in AF patients newly starting VKAs is sub-optimal. Previous coronary artery disease and concomitant use of amiodarone were identified as independent variables affecting the poor quality of VKA therapy during the first year.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Registries; Stroke; Vitamin K

The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants (DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person-year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), and breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real-world cohort of patients with NVAF followed for up to 5 years.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Correlation of Data; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Neoplasms; Proportional Hazards Models; Risk Assessment; Risk Factors; Vitamin K

Gastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.. This is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012-2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case-control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.. 98 376 patients on NOACs (median age: 75 years (IQR: 68-82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).. Concomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Male; Risk Factors; Stroke; Vitamin K

We characterized the utilization and long-term treatment persistence of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF) and liver disease.. Using the UK Clinical Practice Research Datalink, we assembled a population-based cohort of NVAF patients with liver disease initiating oral anticoagulants between 2011 and 2020. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) of the association between patient characteristics and initiation of DOACs vs vitamin K antagonists (VKAs). Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of the association between patient characteristics and the switch from VKAs to DOACs vs remaining on VKAs. We also assessed the 5-year treatment persistence with DOACs vs VKAs, and whether ischemic stroke or bleeding preceded treatment discontinuation.. Our cohort included 3167 NVAF patients with liver disease initiating DOACs (n = 2247, 71%) or VKAs (n = 920, 29%). Initiators of DOACs were more likely to have prior ischemic stroke (OR 1.44, 95% CI 1.12-1.85) than VKA initiators but less likely to have used antiplatelet agents (OR 0.66, 95% CI 0.53-0.82). Patients switching to DOACs were more likely to have used selective serotonin reuptake inhibitors (HR 1.64, 95% CI 1.13-2.37) than those remaining on VKAs. At 5 years, 31% of DOAC initiators and 9% of VKA initiators remained persistent. Only few patients were diagnosed with ischemic stroke or bleeding prior to treatment discontinuation.. Most NVAF patients with liver disease initiated treatment with DOACs. Long-term persistence with DOACs was higher than with VKAs but remained relatively low.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Stroke; Liver Diseases; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Non-Vitamin K antagonist oral anticoagulants (NOACs) emerged as an alternative with comparable or superior efficacy and safety to vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (AF).. The aim of the current study was to investigate the patterns, predictors, timelines and temporal trends of shifting from VKAs to NOACs.. In this retrospective observational study, the computerized database of a large healthcare provider in Israel, Maccabi Healthcare Services, was searched to identify patients with AF for whom either a VKA or NOAC was prescribed between 2012 and 2015. Time from diagnosis to therapy initiation and to shifting between therapies was evaluated.. Out of 6987 eligible AF incident patients, 2338 (33.4%) initiated treatment with a VKA and 2221 (31.7%) with a NOAC. In addition, 5259 prevalent patients were analyzed. During the study period, NOAC prescriptions proportion among the newly diagnosed cases increased from 32 to 68.4% (p for trend <  0.001). The median time from diagnosis to first dispensing was greater in NOAC than VKA and decreased among patients treated with NOAC during the study period (2012: 1.9 and 0.3 months, 2015: 0.7 and 0.2 months, respectively). During follow-up, 3737 (49%) patients (54.3% and 47.1% of the incident and prevalent cases, respectively), shifted from a VKA to a NOAC, after a median of 22 months and 39 months in the incident and prevalent cases, respectively, decreasing throughout the study period. Female gender, younger age, southern district, higher CHADS. Shifting from VKA to NOAC occurred in 50% of the cases, more frequently among incident cases, and younger patients with greater stroke risk. Shifting from a NOAC to a VKA was much less frequent, yet it occurred more often in incident cases and decreased over time. A socially and economically sensitive program to optimize the initiation of OAC therapy upon diagnosis is warranted.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Databases, Factual; Drug Substitution; Drug Utilization; Female; Humans; Incidence; Israel; Male; Middle Aged; Practice Patterns, Physicians'; Prevalence; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Cognition; Dementia; Humans; Vitamin K

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Hemorrhage; Humans; Italy; Male; Vitamin K

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r

Topics: 4-Hydroxycoumarins; Aortic Valve Stenosis; Atrial Fibrillation; Biomarkers; Calcium-Binding Proteins; Cardiovascular Diseases; Cohort Studies; Dietary Supplements; Extracellular Matrix Proteins; Female; Heart Disease Risk Factors; Humans; Indenes; Liver; Male; Matrix Gla Protein; Middle Aged; Nutritional Status; Protein Precursors; Prothrombin; Renal Dialysis; Uremia; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dementia; Female; Global Health; Humans; Incidence; Male; Risk Assessment; Risk Factors; Stroke; Vitamin K

Dabigatran is a direct thrombin inhibitor approved for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Real-world data about patient preference, satisfaction and convenience in patients in Asia are not available. The study aimed to explore the perception of patients with newly diagnosed NVAF regarding dabigatran versus vitamin K antagonists (VKAs), when used for stroke prevention.. This was a multinational, multicentre, non-interventional study involving 49 sites across 5 countries in South East Asia and South Korea where 934 patients newly diagnosed with NVAF were initiated on either dabigatran (N=591) or VKA (N=343). Data were collected at baseline and over two follow-up visits across 6 months. Treatment satisfaction and patient convenience were evaluated using the Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2).. In this study, dabigatran is associated with better patient perception in terms of treatment convenience and satisfaction compared with VKAs when used for stroke prevention in newly diagnosed NVAF patients from South East Asia and South Korea.. NCT02849509.. Patient satisfaction with dabigatran versus VKAs in South East Asia. Patients with atrial fibrillation are at high risk of stroke and require anticoagulants for stroke prevention. Two such anticoagulants are dabigatran and VKAs. We wanted to compare the extent of satisfaction and treatment convenience among newly diagnosed patients with atrial fibrillation from the South East Asian region when they were given either dabigatran or VKAs. Consenting patients filled out a standardised questionnaire called the PACT-Q2 over three visits after they were started on either dabigatran (591 patients) or VKAs (343 patients). We found that satisfaction and convenience were significantly higher when patients received dabigatran than when they received VKAs.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Asia, Southeastern; Atrial Fibrillation; Dabigatran; Female; Follow-Up Studies; Humans; Male; Patient Satisfaction; Perception; Prevalence; Republic of Korea; Retrospective Studies; Risk Management; Stroke; Time Factors; Vitamin K

To examine the risk of arterial thromboembolism, bleeding, and all-cause mortality in atrial fibrillation (AF) patients treated with direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) undergoing transcatheter aortic valve implantation (TAVI).. In this nationwide observational cohort study, 735 patients undergoing TAVI from 1 January 2012 to 30 June 2017 with a history of AF and who were treated with oral anticoagulants were identified using data from Danish nationwide registries. Of these, 219 (29.8%) and 516 (70.2%) patients were treated with DOACs and VKAs, respectively. The DOAC group was characterized by a higher prevalence of previous arterial thromboembolism and a lower prevalence of chronic kidney disease compared with the VKA group. The distribution of age, sex, CHA2DS2-VASc and HAS-BLED scores, and concomitant antiplatelet therapy was similar between groups. Compared with VKA, treatment with DOACs was not associated with a significantly different 3-year absolute risk of arterial thromboembolism [9.6% (95% confidence interval, CI 4.7-16.5%) vs. 7.4% (95% CI 4.9-10.5%) in the DOAC and VKA group, respectively], bleeding [14.3% (95% CI 7.6-22.9%) vs. 13.3% (95% CI 9.9-17.1%)], or all-cause mortality [32.7% (95% CI 21.8-44.0%) vs. 32.0% (95% CI 26.8-37.3%)]. In adjusted analyses, treatment with DOACs, when compared with VKAs, was not associated with a significantly different rate of arterial thromboembolism [hazard ratio (HR) 1.23 (95% CI 0.58-2.59)], bleeding [HR 1.14 (95% CI 0.63-2.06)], or all-cause mortality [HR 0.93 (95% CI 0.61-1.40)].. In patients with AF undergoing TAVI, treatment with DOACs was not associated with a significantly different risk of arterial thromboembolism, bleeding, or all-cause mortality compared with VKA.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Thromboembolism; Transcatheter Aortic Valve Replacement; Vitamin K

In atrial fibrillation (AF) patients 150 mg b.i.d. dabigatran is the standard dose, yet guidelines recommend 110 mg b.i.d. when bleeding risk is high. It is unknown to which extend these recommendations are followed in patients switching from vitamin K antagonist (VKA) to dabigatran. The aim of this study was to investigate if AF patients are switched from VKA to the appropriate dose of dabigatran.. Using nationwide registries (22 August 2011 to 31 December 2012), we identified VKA-experienced AF patients with available creatinine values who switched to dabigatran. European guidelines criteria 2012 on dabigatran dosing were examined: age ≥80 years, HAS-BLED ≥3, estimated glomerular filtration rate (eGFR)<50 mL/min/1.73 m2, or use of interacting drugs. We identified 1626 VKA-experienced AF patients who switched to dabigatran 110 mg (820 patients) or 150 mg (806 patients). Patients who switched to 110 mg compared with 150 mg were older [median age 82 years (Q1-Q3: 77-86) vs. 68 years (Q1-Q3: 64-74)], more often females (54% vs. 35%), had a higher comorbidity burden, higher proportion with CHA2DS2-VASc score ≥2 (98% vs. 80%), and more with a HAS-BLED score ≥3 (46% vs. 28%). Patients switched to 110 mg had a higher absolute risk of mortality compared with patients switched to 150 mg. Overall, 26% were inappropriately dosed and 14% were switched to 110 mg although the higher dose was indicated. Furthermore, 39% of patients switched to 150 mg fulfilled one or more criteria for 110 mg, this mostly driven by high HAS-BLED scores (28.2% of patients on 150 mg). Female sex, age ≥80 years, eGFR < 50 mL/min/1.73 m2, drugs interacting with dabigatran, and prior bleeding were associated with switch to 110 mg. Patients inappropriately dosed had similar risk of mortality as patients appropriately dosed.. Among VKA-experienced AF patients one in four were switched to a dabigatran dose contrary to guideline recommendations.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Vitamin K

Cerebral thromboembolic events are well-known complications of pulmonary vein isolation (PVI) and can manifest as stroke or silent cerebral embolic lesions. The aim of this study was to compare the incidence of cerebral embolic lesions (including silent cerebral embolism and stroke) after AF ablation in patients on vitamin K antagonists versus patients on non-vitamin K-dependent oral anticoagulants, and to identify corresponding clinical and procedural risk factors.. A total of 421 patients undergoing PVI were prospectively included into the study. Of these, 43.7% were on VKA and 56.3% on NOAC treatment (dabigatran, rivaroxaban, apixaban, and edoxaban). In the NOAC group, 38% of patients had an interruption of anticoagulation for 24-36 h. All patients underwent pre- and postprocedural cerebral magnetic resonance imaging.. Periprocedural cerebral lesions occurred in 13.1% overall. Of these, three (0.7%) resulted in symptomatic cerebrovascular accidents and 52 (12.4%) in silent cerebral embolic lesions. Incidence of cerebral lesions was significantly higher in patients on NOAC compared with VKA (16% vs. 9.2%, respectively, p = 0.04), and in patients who had intraprocedural cardioversions compared with no cardivoersions (19.5% vs. 10.4%, respectively, p = 0.03). In multivariate analysis, both parameters were found to be independent risk factors for cerebral embolism. No significant difference between interrupted and uninterrupted NOAC administration could be detected.. In patients undergoing AF ablation, we identified the use of NOAC and intraprocedural cardioversion as independent risk factors for the occurrence of periprocedural cerebral embolic lesions.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Stroke; Thromboembolism; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Vitamin K

Studies on adherence and persistence with non-vitamin K oral anticoagulant (NOAC) treatment have relied on data from the early years of NOAC availability. We aimed to study long-term adherence and persistence with NOACs and their association with stroke risk.. From the Stockholm Healthcare database, we included 21 028 atrial fibrillation patients claiming a first NOAC prescription from July 2011 until October 2018, with more than 1000 patients having more than 5 years of follow-up (median: 2.0, interquartile range: 1.0-3.2). Persistence rates, defined as continuing to claim NOAC prescriptions within a 90-day gap, decreased to 70% at the end of follow-up. However, 85% of the patients were treated at the end of the study due to reinitiations. Adherence, calculated as medication possession rate (MPR) in 3 and 6-month intervals among persistent users, remained stable at 90%, with 75% of patients having an MPR >95% throughout the study period. Using a case-control design, we calculated associations of persistence and adherence with stroke risk, adjusting for potential confounders. The outcome was a composite of ischaemic or unspecified stroke and transient ischaemic attack. Non-persistence and poor adherence were both associated with increased stroke risk [non-persistence adjusted odds ratio (aOR): 2.05; 95% confidence interval (CI): 1.49-2.82, 1% reduction MPR aOR: 1.03; CI: 1.01-1.05]. There was no association between non-persistence or poor adherence and the falsification endpoints; fractions and respiratory infections, indicating no 'healthy-adherer' effect.. Persistence rates decreased slowly over time, but persistent patients had high adherence rates. Both non-persistence and poor adherence were associated with an increased stroke risk.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Following hematuria, it is uncertain to what extent a vitamin K antagonist (VKA) or non-VKA oral anticoagulant (NOAC) is resumed, and the risks of ischemic stroke/systemic embolism and major bleeding associated with NOAC and VKA resumption are unknown. A cohort study was conducted using electronic medical records collected from 2009 to 2017 at a multicenter healthcare provider in Taiwan. The cohort included 4155 atrial fibrillation patients receiving anticoagulant therapy with hematuria (age: 71.4 ± 11.2 years; 48.8% female). Within 90 days following hematuria, 3287 patients (79.1%) resumed oral anticoagulants including VKA (n = 1554, 37.4%) and NOACs (n = 1733, 41.7%), whereas 868 patients did not resume anticoagulant. Follow-up was initiated 90 days after the occurrence of hematuria, and time-varying multiple Cox regression analyses were used for comparisons between the resumption of NOAC and VKA. The event rates per 100 person-years in the VKA resumption and NOAC resumption groups were 3.04 and 3.28 for ischemic stroke/systemic embolism, and 2.63 and 2.92 for major bleeding, respectively. Patients resuming NOAC had similar risks of ischemic stroke/systemic embolism (hazard ratio 1.14, 95% CI 0.75-1.74) and major bleeding (hazard ratio 1.12, 95% CI 0.72-1.74) compared with those resuming VKA. Since 2011, the proportion of NOAC resumption has increased, whereas the proportions of VKA resumption and non-resumption have decreased. In conclusion, more and more patients who suffer a hematuria while on oral anticoagulant therapy resume NOAC. Patients resuming NOAC have similar risks of ischemic stroke/systemic embolism and major bleeding compared with those resuming VKA.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hematuria; Hemorrhage; Humans; Incidence; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan; Vitamin K

Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population.. This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin.. This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB.. Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk vs warfarin.. Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Dabigatran; Frail Elderly; Hemorrhage; Humans; Propensity Score; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; United States; Vitamin K; Warfarin

The introduction of direct oral anticoagulants (DOACs) has broadened the treatment arsenal for nonvalvular atrial fibrillation, but observational studies on the benefit-risk balance of DOACs compared to vitamin K antagonists (VKAs) are needed. The aim of this study was to characterize the risk of major bleeding in DOAC users using longitudinal data collected from electronic health care databases from 4 different EU-countries analysed with a common study protocol.. A cohort study was conducted among new users (≥18 years) of DOACs or VKAs with nonvalvular atrial fibrillation using data from the UK, Spain, Germany and Denmark. The incidence of major bleeding events (overall and by bleeding site) was compared between current use of DOACs and VKAs. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals (CI) and adjust for confounders.. Overall, 251 719 patients were included across the 4 study cohorts (mean age ~75 years, % females between 41.3 and 54.3%), with overall hazard ratios of major bleeding risk for DOACs vs VKAs ranging between 0.84 (95% CI: 0.79-0.90) in Denmark and 1.13 (95% CI 1.02-1.25) in the UK. When stratifying according to the bleeding site, risk of gastrointestinal bleeding was increased by 48-67% in dabigatran users and 30-50% for rivaroxaban users compared to VKA users in all data sources except Denmark. Compared to VKAs, apixaban was not associated with an increased risk of gastrointestinal bleeding in all data sources and seemed to be associated with the lowest risk of major bleeding events compared to dabigatran and rivaroxaban.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Germany; Hemorrhage; Humans; Male; Rivaroxaban; Spain; Stroke; Vitamin K

Digoxin treatment has come under scrutiny in recent years after reports from several studies that it is associated with increased mortality in patients with atrial fibrillation (AF). The clinical effects of digoxin on mortality were closely related to serum digoxin concentrations (SDC) in these studies. In the present work, we evaluated the role of the SAMe-TT. Medical records from our institution were screened for patients who were under digoxin treatment between 2008 and 2018. A total of 2418 patients for whom SDC were recorded were included in the study. An SDC of <0.5 or >1.2 ng/ml was defined as being out of the therapeutic range (oTR).. In multivariable regression analyses, abnormal body mass index (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.29-1.95, p < 0.01), white blood cell count (OR: 1.12, 95% CI: 1.01-1.27, p < 0.01), and the modified SAMe-TT. Digoxin is still widely used in the treatment of heart failure and AF despite concerns about the increased risk of mortality when levels are oTR. In the present study, the modified SAMe-TT. HINTERGRUND: In den letzten Jahren wurde die Digoxintherapie kritisch betrachtet, nachdem verschiedene Studien über einen Zusammenhang mit erhöhter Mortalität bei Patient(inn)en mit Vorhofflimmern (VF) berichtet hatten. Die klinischen Wirkungen von Digoxin auf die Mortalität waren eng mit den Serumdigoxinkonzentrationen (SDC) in diesen Studien verknüpft. In der vorliegenden Arbeit untersuchten die Autor(inn)en die Rolle des SAMe-TT. Die Krankenakten der Klinik der Autor(inn)en wurden auf Patient(inn)en hin durchsucht, die zwischen 2008 und 2018 mit Digoxin behandelt wurden. In die Studie wurden 2418 Patient(inn)en einbezogen, für welche die SDC dokumentiert waren. Eine SDC von <0,5 oder >1,2 ng/ml wurde als außerhalb der therapeutischen Breite liegend definiert.. In multivariablen Regressionsanalysen wurden ein anomaler Body Mass Index (Odds Ratio, OR: 1,59; 95 %-Konfidenzintervall, 95 %-KI: 1,29–1,95; p < 0,01), die Leukozytenzahl (OR: 1,12; 95 %-KI: 1,01–1,27; p < 0,01) und der modifizierte SAMe-TT. Weiterhin ist Digoxin zur Therapie der Herzinsuffizienz und des VF weit verbreitet – trotz Bedenken hinsichtlich des erhöhten Mortalitätsrisikos, wenn die Spiegel außerhalb der therapeutischen Breite liegen. In der vorliegenden Studie erwies sich der modifizierte SAMe-TT

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Humans; Treatment Outcome; Vitamin K

Older hip fracture patients are still challenging in daily clinical practice. Due to the high prevalence of osteoporosis and atrial fibrillation in this age group, the number of fragility fracture patients under oral anticoagulation (OAC) increases. The outcome is still disappointing, short- and long-term mortality and morbidity is high. The impact of pre-existing OAC is not yet clear, especially regarding new OAC drugs like Factor Xa inhibitors (FXa). The purpose of our study was to compare the short-term outcome of older hip fracture patients, without OAC (controls), on Vitamin K antagonists (VKA) and on FXa.. The study is a retrospective case-control study including patients older than 70 years who sustained hip fractures caused by an inadequate trauma and treated at a level 1 trauma center from February 2017 to June 2018. Patient's information was taken from patient's charts. 102 cases were analysed, 61 controls, 41 on OAC (15 on VKA and 26 on FXa). As outcome parameter we defined mortality, perioperative complications, bleeding, need of blood supplements, delay of surgery, length of stay, and a combined outcome parameter (mortality, myocardial infarction, stroke, thromboembolic events, blood preservations, re-vision surgery, major bleeding and decline of hemoglobin).. Eight patients died during hospital stay, in-hospital mortality was 7.8%. The highest mortality rate was found in patients on VKA (20%), compared to patients on FXa (3.8%) and controls (6.6%). However, mortality rate did not differ significantly within the groups. The combined endpoint was significantly more frequently seen in patients on OAC compared to controls (p = 0.006). No difference was observed between patients on VKA or FXa. Mean time to surgery and LOS was significantly longer in patients on OAC compared to controls. No significant differences were seen between VKA and FXa.. In our study OAC was significantly associated with worse outcome compared to controls. Marginal differences were observed between patients on FXa or VKA. Further studies involving a higher number of patients are necessary to confirm our results. At that time, some our results have to interpreted carefully and need confirmation.

Topics: Anticoagulants; Atrial Fibrillation; Case-Control Studies; Factor Xa Inhibitors; Hip Fractures; Humans; Retrospective Studies; Treatment Outcome; Vitamin K

To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use.. Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46-0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31-0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79-1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls.. Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Vitamin K

Patients with systemic right ventricle (sRV), including transposition of great arteries (TGA) after atrial switch procedure and congenitally corrected transposition of great arteries (ccTGA), may require anticoagulation for thromboembolism (TE) prevention. In the absence of data on non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonists (VKAs) remain the agent of choice. We investigated the safety, efficacy and feasibility of NOACs treatment in adults with sRV in a worldwide study.. This is an international multicentre prospective study, using data from the NOTE registry on adults with sRV taking NOACs between 2014 and 2019. The primary endpoints were TE and major bleeding (MB). The secondary endpoint was minor bleeding.. In this prospective study, NOACs appear to be well-tolerated, with excellent efficacy and safety at mid-term in patients with sRV.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Female; Heart Ventricles; Humans; Male; Prospective Studies; Registries; Stroke; Thromboembolism; Vitamin K

The purpose of the present study was to compare the long-term effectiveness and safety of newly initiated anticoagulation with edoxaban (EDO) versus uninterrupted vitamin K antagonist (VKA) therapy in patients with atrial fibrillation (AF) scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC).. A propensity score-matched cohort observational study was performed comparing the safety and effectiveness of edoxaban versus well-controlled VKA therapy among a cohort of consecutive non-valvular AF patients scheduled for DCC. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE).. A total of 130 AF patients receiving edoxaban 60-mg (EDO) treatment were compared with the same number of VKA recipients. The cumulative incidence of major bleedings was 1.54% in the EDO group and 3.08% in the VKA group (P = 0.4). The cumulative incidence of thromboembolic events was 1.54% in the EDO group and 2.31% in the VKA group (P = 0.9). A non-significant trend in improved adherence was observed between the EDO and VKA groups with a total anticoagulant therapy discontinuation rate of 4.62% (6/130) vs 6.15% (8/130), respectively (P = 0.06).. Our study provides the evidence of a safe and effective use of edoxaban in this clinical setting, justified by no significant difference in major bleedings and thromboembolic events between edoxaban and well-controlled VKA treatments.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Electric Countershock; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Medication Adherence; Middle Aged; Propensity Score; Pyridines; Stroke; Thiazoles; Vitamin K

Silent cerebral microembolic events (SCE) after duty-cycled ablation of atrial fibrillation using PVAC have been detected by cerebral magnet resonance imaging (MRI) in a substantial number of patients. The purpose of this study was to investigate if uninterrupted oral anticoagulation with non-vitamin K antagonists (NOACs) compared with vitamin K antagonists (VKA) affects the incidence of SCE after pulmonary vein isolation (PVI) using PVAC Gold.. Eighty-four consecutive patients (62 ± 15 years, 58% male) undergoing a first PVI were prospectively enrolled. Of these, 42 were on VKA and 42 on uninterrupted NOAC treatment. An activated clotting time (ACT) ≥ 350 s was targeted for ablation.. Cerebral MRI the day after PVI revealed acute diffusion-weighted positive lesions in 11/42 (26%) VKA compared with 14/42 (33%) in NOAC patients (p = 0.634). No differences were found for lesion size, number of lesions/patient, and number of lesions indicating cerebral infarction (2.4% for VKA and 4.8% for NOAC patients). Seventy-five percent of NOAC patients with sporadic ACT levels < 300 s during PVI developed SCE compared with 22% of corresponding VKA patients (p = 0.030). VKA and NOAC subgroups with ACT ≥ 350 s had no reduced incidence of SCE compared with ACT 300-350 s.. A significant, but comparable, number of patients under uninterrupted anticoagulation with VKA or NOACs still experience SCE after PVAC Gold PVI. NOAC patients with sporadic subtherapeutic ACT levels during PVI are at the highest risk for SCE while permanent ACT levels ≥ 350 s did not further reduce the incidence of SCE in both groups.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Gold; Humans; Incidence; Male; Treatment Outcome; Vitamin K

The aim of this analysis was to evaluate the burden and cost of complications due to poor anticoagulation control in patients with nonvalvular atrial fibrillation (NVAF) treated with vitamin K antagonists (VKA) in Spain.. An analytical model was used to estimate annual differences in ischemic stroke, major bleeding, deaths, costs, and potential years of life lost between patients with poor anticoagulation control (time in therapeutic range <65%) and adequate control (time in therapeutic range ≥ 65%) with a 1-year time horizon. Information on the target population (patients ≥ 65 years), event rates, and costs were obtained from national sources. Direct costs in euros (2018) were included from the perspective of the national health system (NHS) and direct and indirect costs from the societal perspective. A sensitivity analysis was performed with post-hoc data from the SPORTIF III/V trials.. We analyzed a hypothetical cohort of 594 855 patients, 48.3% with poor anticoagulation control, with an increase of 2321 ischemic strokes, 2236 major bleeding events and 14 463 deaths, and an annual incremental cost between €29 578 306 from the NHS perspective and €75 737 451 from the societal perspective. The annual impact of mortality was 170 502 potential years of life lost. The results of the sensitivity analysis showed that the annual cost would reach €97 787 873 from the societal perspective.. Poor anticoagulation control with AVK has a strong impact on loss of health and on increased spending for the NHS.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Humans; Spain; Stroke; Vitamin K

The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes.. This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months.. Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51).. Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Female; Fibrinolytic Agents; Humans; Ischemic Stroke; Male; Middle Aged; Vitamin K

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are a high-risk subset of patients, whose optimal antithrombotic treatment strategy, involving a combination of anticoagulant and antiplatelet agents, has not been well defined. Our study aims to investigate contemporary "real-world" trends of antithrombotic treatment strategies in AF patients undergoing PCI, as well as identify factors affecting decision-making at hospital discharge.. "Real-world" data were retrieved from the GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) registry, a contemporary, nationwide, multicenter, observational study of AF patients undergoing PCI. Characteristics of patients discharged on triple antithrombotic therapy (TAT) or dual antithrombotic therapy (DAT) were compared in order to identify factors that could influence treatment decisions.. A total of 654 patients were enrolled (42% with stable coronary artery disease, 58% with acute coronary syndrome). TAT was adopted in 49.9% and DAT in 49.2% of patients at discharge. Regarding anticoagulants, the vast majority of patients (92.9%) received non-vitamin K antagonist oral anticoagulants (NOACs) and only 7.1% received vitamin K antagonists (VKAs). Dyslipidemia, insulin-dependent diabetes mellitus, prior myocardial infarction, acute coronary syndrome at presentation, and regional variations were predictive of TAT adoption, whereas the use of NOACs or ticagrelor was predictive of DAT adoption.. Contemporary "real-world" data concerning antithrombotic treatment in AF patients undergoing PCI indicate a strong shift towards the use of NOACs instead of VKAs, along with a large subset of patients adopting an aspirin-free strategy early after index PCI, with clinical as well as treatment characteristics affecting decision-making.. ClinicalTrials.gov Identifier: NCT03362788 (First Posted: December 5, 2017).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Residence Characteristics; Sociodemographic Factors; Vitamin K

Hemorrhage occurs in 7-10% of patients treated with vitamin K antagonist (VKA), with major bleeding in 1-3%. Impact of nutritional status on the bleeding risk of patients on anticoagulants is still poorly documented. Our study aimed to analyze the link between the nutritional status of patients on VKA and the occurrence of hemorrhagic events. We also analyzed micronutrients status.. A case-control, monocentric, and prospective study was conducted from August 2012 to October 2015. The case patients were those presenting with major bleeding and control patients those without any bleeding under VKA treatment.. Overall, 294 patients under VKA treatment were paired according to age, gender, and index normalized ratio (INR). Out of these, 98 (33.3%) had major bleeding and 196 (66.7%) did not have any bleeding. Additionally, more than two-thirds of patients displayed undernutrition, which was more prevalent in bleeding than non-bleeding patients (OR = 1.85, CI95%: 1.07-3.21). There was a higher bleeding risk for those with severe undernutrition (OR = 2.66, CI95%: 1.58-4.46), with no difference found concerning moderate undernutrition. Bleeding patients had lower plasma-zinc concentrations than non-bleeding patients (9.4 ± 3.6 vs. 10.5 ± 3.7 μmol/L, p = 0.003); among them, there was a higher rate of patients with plasma zinc under 5 μmol/L (9% vs. 2%, p < 0.001).. Patients with undernutrition on VKA exhibit a significantly higher bleeding risk, which increases three-fold in case of severe undernutrition. The evaluation of nutritional status provides additional, valuable prognosis information prior to initiating VKA therapy. CLINICALTRIALS.. NCT01742871.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Female; Hemorrhage; Humans; Male; Malnutrition; Prospective Studies; Risk Factors; Vitamin K

Direct oral anticoagulants (DOACs) have emerged as the preferred choice of oral anticoagulation in patients with atrial fibrillation. Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing electrical cardioversion (ECV); however, there is limited real-world data.. To evaluate the outcome of patients undergoing an elective ECV for atrial tachyarrhythmia in a tertiary referral center who were treated with DOAC or vitamin K antagonist (VKA) without routine trans esophageal echocardiography (TEE).. This was a retrospective single-center cohort study of consecutive patients undergoing an elective ECV for atrial tachyarrhythmia from January 2013 to February 2020. The primary endpoints were thromboembolism (composite of stroke, transient ischemic attack or systemic embolism) and major bleeding events within 60 days.. In a real-world population, the rates of thromboembolism and major bleeding events were low after elective ECV in patients using DOAC or VKA, even without routine TEE.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Electric Countershock; Female; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Vitamin K

Many adult patients with Fontan circulation are treated with antithrombotic agents, including direct oral anticoagulants (DOACs). However, few studies have investigated the efficacy, feasibility, and safety of DOACs in adult patients with Fontan circulation.. In this retrospective cohort study, clinical records of 139 adult patients with Fontan circulation (70 females, 50.4%) from April 2015 to March 2018 were reviewed and classified into five groups according to the therapeutic agents used: DOAC (n = 36), vitamin K antagonist (VKA; n = 41), antiplatelet drug (n = 43), combination of an antiplatelet and anticoagulant (n = 14), and no-antithrombotic prophylaxis (n = 5). In a 1114-patient-year follow-up, 28 major events occurred, including 10 thrombotic and 18 bleeding events; 11 of 18 (61%) female patients had severe menorrhagia. The incidence (% patient-years) of major events was 0.6, 1.42, 3.74, and 5.13 in the DOAC, antiplatelet, VKA, combination, and no-antithrombotic groups, respectively. The Cox proportional hazards analysis revealed that the DOAC group had a lower rate of primary endpoints than the VKA group in males.. DOAC may be a safe antithrombotic agent for use in adult patients with Fontan circulation, particularly in males. However, these findings should be confirmed in multi-institutional prospective studies.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Female; Fontan Procedure; Humans; Male; Prospective Studies; Retrospective Studies; Vitamin K

Our objectives were to evaluate the risk of adverse events in a 'real-world' vs 'clinical trial' cohort of atrial fibrillation (AF) patients with chronic kidney disease (CKD).. We studied patient-level data for vitamin K antagonist-treated AF patients with a creatinine clearance <60 mL/min from the Murcia AF Project and AMADEUS trial. The study end-points were ischaemic stroke, major bleeding, all-cause mortality, myocardial infarction and intracranial haemorrhage.. This study included 1,108 AF patients with CKD. The annual rate of the composite study outcome of ischaemic stroke, major bleeding and all-cause mortality was higher in the real-world (13.4%) vs AMADEUS (6.6%) cohort with an IRR of 2.04 (95% CI,1.34-3.09), P < .001. Individual annual rates of major bleeding, all-cause mortality and non-cardiovascular mortality were significantly greater in the real-world cohort. Similar findings were demonstrated even after multivariable adjustment, with the composite outcome HR of 2.85 (95% CI,1.74-4.66), P < .001. In a propensity score matched cohort, this risk remained significantly higher in the real-world cohort (IRR 2.95 [95% CI,1.03-10.28], P = .027), as did the risk of major bleeding and all-cause mortality.. Vitamin K antagonist-treated AF patients with CKD are exposed to significant annual rates of major adverse events including all-cause mortality. This risk may be under-appreciated in the idealised environment of randomised controlled trials.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Renal Insufficiency, Chronic; Stroke; Vitamin K

There is a high prevalence of atrial fibrillation (AF) in patients undergoing haemodialysis. Oral anticoagulant therapy with vitamin K antagonists (VKAs) is the only accepted treatment for the prevention of thromboembolism in haemodialysis patients with AF. However, in this population, the risk of bleeding is greatly increased. The aim of the study was to evaluate the ability of treatment quality indicators of VKA therapy to predict mortality and bleedings in a population of haemodialysis patients with AF.. A total of 129 patients were included in this cohort study. Deaths and bleeding events were recorded during a follow-up of 4 years. In all patients, International Normalized Ratio (INR) values were assessed at least once a month. Time in therapeutic range (TTR) and INR variability, as measured by the standard deviation of INR, were updated at each INR measurement. A Cox model with time-dependent co-variates and sandwich variance was applied.. During follow-up, 71 patients died and 55 bleeding episodes occurred in 31 patients. INR variability was the only indicator associated with both mortality (hazard ratio [HR]=1.67, 95% confidence interval [CI] 1.12; 2.49, p=0.012) and bleeding (HR=2.85, 95% CI: 1.71; 4.75, p=0.0001). HR of mortality was higher in patients with INR >3 (HR=2.06, 95% CI: 1.09; 3.88, p=0.0259) than in subjects in therapeutic range 2

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; International Normalized Ratio; Quality Indicators, Health Care; Renal Dialysis; Stroke; Vitamin K

In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y. In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial.. Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min. The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Kidney; Male; Middle Aged; Percutaneous Coronary Intervention; Pyrazoles; Pyridones; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOAC) present several advantages over vitamin K antagonists, but data with respect to their use in patients with chronic kidney disease is limited. The decision to use oral anticoagulation as well as the choice of the molecule may be difficult in these patients. In patients with moderate kidney disease, NOACs appear to be safe and effective. In advanced kidney disease, they should be used with prudence, after careful assessment of risks and benefits, and at adapted doses. In end stage kidney disease, evidence is weak, suggesting an unfavourable risk benefit ratio. Prescription of oral anticoagulation in these patients has to be individualised in a shared decision making process.. Les anticoagulants oraux directs (ACOD) présentent plusieurs avantages sur les antivitamines K, mais les données concernant leur utilisation en cas d’insuffisance rénale avancée restent rares. Le choix d’anticoaguler et celui de la molécule sont particulièrement ardus chez ces patients. En cas d’insuffisance rénale légère à modérée, les ACOD présentent un profil de sécurité et d’efficacité satisfaisant. En cas d’insuffisance rénale sévère, leur utilisation doit être prudente, avec une évaluation soigneuse des risques et bénéfices, et en adaptant la posologie. Chez les patients avec insuffisance rénale terminale, l’évidence est faible et suggère un rapport bénéfice/risque défavorable pour l’anticoagulation orale. La décision d’anticoaguler et le choix de la molécule nécessiteront une approche individualisée et une décision partagée avec le patient.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Fibrinolytic Agents; Humans; Stroke; Vitamin K

Direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for the prevention of stroke in atrial fibrillation (AF) patients with elevated stroke risk. Possible antiarrhythmic effects of DOACs have been discussed. We analyzed impact of DOAC treatment on recurrence-free survival after AF catheter ablation.. Two-hundred and thirty-nine consecutive patients (median age 57 [IQR 48-64] years, 26.4% female) undergoing ablation for paroxysmal AF were included into this study. 68.6% of them received DOACs (DOAC group), 31.4% VKA (VKA group). The primary outcome was arrhythmia-free one-year survival.. Despite baseline characteristics favouring a better outcome of DOAC patients, arrhythmia-free survival was similar in both groups. Consequently, DOAC treatment did not have clinically relevant antiarrhythmic properties in these patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Humans; Male; Middle Aged; Stroke; Vitamin K

The use of anticoagulants to prevent embolic events in Spain is very high, tending to a progressive increase. For this reason, we intend to analyse the mortality of patients from a metropolitan area of Granada treated with vitamin K antagonist anticoagulants (VKA), over 2 non-consecutive years.. Longitudinal, observational, retrospective study of 205 patients treated with VKA. Sociodemographic data, previous clinical conditions, pathology causing VKA treatment, degree of control and mortality were collected 2 years after the start of the study.. Average age, 76±11.8 years (57.56% women). Two-year mortality was 22.4%, with a significant increase depending on age (p<.001) and years of treatment (p<.001). Patients with dementia (p<.05), with chronic kidney disease (p<.01) or with chronic obstructive pulmonary disease (p<.01) also presented higher mortality. Multivariate analysis showed significant effect of chronic kidney disease (odds ratio=4.075), chronic obstructive pulmonary disease (odds ratio=3.694), and years of treatment (odds ratio=1.236).. At 2 years of follow-up, 1 in 5 patients treated with VKA died. The presence of chronic kidney disease, chronic obstructive pulmonary disease and a longer treatment time were independently associated with this increase of mortality. Most of the patients were anticoagulated by atrial fibrillation, they were elderly and had a high prevalence of comorbidities.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Primary Health Care; Retrospective Studies; Stroke; Vitamin K

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Vitamin K

There has been a rapid increase in the use of non-vitamin K-antagonist oral anticoagulants (NOAC). Current guidelines recommend dose adjustments be made in accordance with certain criteria for each NOAC. This study is aimed at determining whether or not NOAC were prescribed for non-valvular atrial fibrillation (AF) in guideline-recommended doses in community-dwelling older adults.. Older adults taking NOAC for non-valvular AF presenting to a cardiology outpatient clinic for the first time were included in the study. The NOAC dose for each patient was assessed based on the recommendations of the European Society of Cardiology and were categorized as appropriate or inappropriate (low or high dose). The patients were also evaluated for demographic data, diseases, CHA2DS2-VASc score, HASBLED score, frailty and falls in the previous year.. A total of 302 older adults were included in the study, with a mean age of 75.5 ± 7.5 years. One hundred eighty-four patients (60.9%) were found to be on appropriate doses of NOAC, while 109 (36.1%) were on inappropriately low doses and nine (2.98%) were on inappropriately high doses. Accordingly, 39.1% of the AF patients were found to be on inappropriate doses of NOAC, 92.4% of which were inappropriately low. A multivariate logistic regression analysis revealed that the only factor associated with inappropriate low-dose NOAC use was patient age (OR = 1.061, 95% CI = 1.009-1.116, p = 0.022).. Our study suggests that the inappropriate use of lower dose NOAC may emerge as a significant problem in outpatient older adults. This inappropriate practice seems to be associated with older age rather than the diseases, CHA2DS2-VASc/HASBLED scores, frailty and presence of falls.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Humans; Outpatients; Stroke; Vitamin K

Drug exposure status based on routinely collected data might be misclassified when the database contains only prescriptions from 1 type of prescriber (e.g. general practitioner and not specialist). This study aims to quantify the impact of such exposure misclassification on the risk of major bleeding and stroke/transient ischaemic attack (TIA)associated with direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs).. Incident anticoagulant users (>12 mo free of anticoagulation use) in the Dutch PHARMO Database Network between 2008 and 2017 were included. Drug exposure was assessed using pharmacy dispensing information. The risks of hospital admission of major bleeding for DOAC vs. VKA users was assessed with Cox regression analysis, where exposure was based on all dispensings, on general practitioner (GP)-prescribed dispensings only or on specialist-prescribed dispensings only. Hazard ratios (HRs) were estimated also for hospitalization for gastrointestinal bleeding, intracranial bleeding and stroke/TIA.. We included 99 182 VKA-initiators and 21 795 DOAC-initiators. Use of DOAC was associated with a lower risk of major bleeding compared to VKA use; HR 0.79 (95% confidence interval 0.70-0.90), 0.78 (0.68-0.91) and 0.62 (0.50-0.76), for exposure based on complete dispensing information, only GP- and only specialist-prescribed dispensings, respectively. Similar results were found for the other bleeding outcomes. For stroke/TIA the HRs were 0.96 (0.84-1.09), 1.00 (0.84-1.18) and 0.72 (0.58-0.90), respectively.. Including only GP-prescribed anticoagulant dispensings in this case did not materially impact the effect estimates compared to including all anticoagulant dispensings. Including only specialist-prescribed dispensings, however, strengthened the effect estimates.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Vitamin K

In atrial fibrillation (AF), lower risks of death and bleeding with non-vitamin-K oral anticoagulants (NOACs) were reported in meta-analyses of controlled trials, but whether these findings hold true in real-world practice remains uncertain. Risks of bleeding and death were assessed in 52 032 patients with newly diagnosed AF enrolled in GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation), a worldwide prospective registry. Baseline treatment was vitamin K antagonists (VKAs) with or without antiplatelet (AP) agents (VKA ± AP) (20 151; 39.3%), NOACs ± AP agents (14 103; 27.5%), AP agents only (10 748; 21.0%), or no antithrombotics (6219; 12.1%). One-year follow-up event rates (95% confidence interval [CI]) of minor, clinically relevant nonmajor (CRNM), and major bleedings were 2.29 (2.16-2.43), 1.10 (1.01-1.20), and 1.31 (1.21-1.41) per 100 patient-years, respectively. Bleeding risk was lower with NOACs than VKAs for any bleeding (hazard ratio (HR) [95% CI]), 0.85 [0.73-0.98]) or major bleeding (0.79 [0.60-1.04]). Compared with no bleeding, the risk of death was higher with minor bleeding (adjusted HR [aHR], 1.53 [1.07-2.19]), CRNM bleeding (aHR, 2.59 [1.80-3.73]), and major bleeding (aHR, 8.24 [6.76-10.04]). The all-cause mortality rate was lower with NOACs than with VKAs (aHR, 0.73 [0.62-0.85]). Forty-five percent (114) of all deaths occurred within 30 days, and 40% of these were from intracranial/intraspinal hemorrhage (ICH). The rates of any bleeding and all-cause death were lower with NOACs than with VKAs. Major bleeding was associated with the highest risk of death. CRNM bleeding and minor bleeding were associated with a higher risk of death compared to no bleeding. Death within 30 days after a major bleed was most frequently related to ICH. This trial was registered at www.clinicaltrials.gov as #NCT01090362.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Registries; Vitamin K

Vitamin K antagonists (VKA) and non-vitamin K oral antagonist anticoagulants (NOAC) are used in the clinic to reduce risk of thrombosis. However, they also exhibit vascular off-target effects. The aim of this study is to compare VKA and NOAC on atherosclerosis progression and calcification in an experimental setup.. Female Apoe. Short-term treatment with warfarin promoted formation of atherosclerotic lesions with a pro-inflammatory phenotype, and more rapid plaque progression compared with control and dabigatran. In contrast, dabigatran significantly reduced plaque progression compared with control. Long-term warfarin treatment significantly increased both presence and activity of plaque calcification compared with control and dabigatran. Calcification induced by warfarin treatment was accompanied by increased presence of uncarboxylated matrix Gla protein. In vitro, both warfarin and thrombin significantly increased VSMC oxidative stress and extracellular vesicle release, which was prevented by dabigatran.. Warfarin aggravates atherosclerotic disease activity, increasing plaque inflammation, active calcification, and plaque progression. Dabigatran lacks undesired vascular side effects and reveals beneficial effects on atherosclerosis progression and calcification. The choice of anticoagulation impacts atherosclerotic disease by differential off target effect. Future clinical studies should test whether this beneficial effect also applies to patients.

Topics: Animals; Anticoagulants; Atherosclerosis; Atrial Fibrillation; Dabigatran; Female; Humans; Mice; Vitamin K; Warfarin

Patient's adherence to oral anticoagulant therapy is essential to prevent and treat thrombotic events.. To assess the patients' adherence Morisky Medication Adherence Scale 8-items was used. The target population included 785 consecutive outpatients, of whom 384 were on Vitamin K Antagonists and 401 on Direct Oral Anticoagulants. Moreover, we evaluate which variable among age, gender, having experienced a thrombotic episode, time in the therapeutic range for patients on Vitamin K Antagonists, being naive and once versus twice daily drug assumption for patients on Direct Oral Anticoagulants, could affect adherence to therapy.. Morisky Medication Adherence Scale 8-items score was 8 in both groups. The intentional non-adherence obtained the lowest score while the unintentional non-adherence is the most frequent problem in patients treated with either Vitamin K Antagonists or Direct Oral Anticoagulants. Age > 75 years, male gender, having experienced a thrombotic episode, being naive and assuming Direct Oral Anticoagulants twice a day were significantly associated with a higher risk to forget assuming the oral anticoagulant, to have more difficulty in remembering to take it or to bring it in case of travel or leaving home. A low percentage of time in therapeutic range was associated with a not regularly assumption of the anticoagulants.. Patients treated with Vitamin K Antagonists or Direct Oral Anticoagulants show a good adherence and persistence to their oral anticoagulant therapy. Several factors have been identified to affect patients' adherence and deserve a careful attention by the doctors at the Anticoagulation Clinic.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Male; Medication Adherence; Thrombosis; Vitamin K

To determine the prevalence of atrial fibrillation (AF) and to assess how these patients are being cared for: what anticoagulants are being prescribed and are they being prescribed as recommended?. Retrospective longitudinal study.. This study was conducted in the Regional Health Administration of Northern Portugal.. This study used a database that included 63526 patients with code K78 of the International Classification of Primary Care between January 2016 and December 2018.. The prevalence of AF among adults over 40 years in the northern region of Portugal was 2.3% in 2016, 2.8% in 2017 and 3% in 2018. From a total of 63 526 patients, 95.8% had an indication to receive anticoagulation therapy. Of these, 44 326 (72.9%) are being treated with anticoagulants: 17 936 (40.5%) were prescribed vitamin K antagonists (VKAs) and 26 390 (59.5%) were prescribed non-VKA anticoagulants. On the other hand, 2688 patients of the total (4.2%) had no indication to receive anticoagulation therapy. Of these 2688 patients, 1100 (40.9%) were receiving anticoagulants.. The prevalence of AF is 3%. Here, we report evidence of both undertreatment and overtreatment. Although having an indication, a considerable proportion of patients (27.1%) are not anticoagulated, and among patients with AF without an indication to receive anticoagulation therapy, a considerable proportion (40.9%) are receiving anticoagulants. The AF-React study brings extremely relevant conclusions to Portugal and follows real-world studies in patients with AF in Europe, presenting some data not yet studied.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Europe; Humans; Longitudinal Studies; Portugal; Retrospective Studies; Stroke; Vitamin K

The role of certain treatments in the development of bone fragility is well known. Since the 2000s, several studies, conducted in patients on long-term anticoagulants have suggested the involvement of vitamin K antagonist (VKA) in the occurrence of osteoporotic fractures. Since their launch in 2008, the new oral anticoagulants (NOACs) have been widely used. Compared to VKA, this drugs' class is associated with a lower fracture risk. Therefore, the presence of risk factors for fracture should be considered when prescribing long-term anticoagulants. In this line, the NOACs seem to be an interesting alternative for patients at risk of fracture requiring a long-term anticoagulation. Nevertheless, certain aspects remain to be clarified.. Le rôle joué par certains traitements pour favoriser une fragilité osseuse est bien connu. Depuis les années 2000, plusieurs études, menées chez des patients anticoagulés au long cours, évoquent l’implication des antivitamines K (AVK) dans la survenue de fractures ostéoporotiques. Depuis leur mise sur le marché en 2008, les nouveaux anticoagulants oraux (NACO) sont largement utilisés. Comparée aux AVK, cette classe médicamenteuse semble associée à un risque fracturaire moindre, menant à considérer la présence de facteurs de risque osseux lors de la prescription d’une anticoagulation au long cours. En ce sens, et bien que certains aspects restent à éclaircir, les NACO semblent être une alternative intéressante chez les patients présentant un risque fracturaire accru et la nécessité d’une anticoagulation au long cours.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Osteoporotic Fractures; Risk Factors; Stroke; Vitamin K

Time in therapeutic range (TTR) measures the stability of the international normalized ratio in patients on vitamin K antagonists (VKA). Low values are associated with poor outcomes. Women were shown to have lower TTR than men, but the causes are poorly defined. It was suggested that women on VKA are older and more morbid than men, and this could affect the stability of anticoagulation. We aimed to identify variables that affect TTR differently in women and men.. This is a retrospective study in patients referred to a University hospital anticoagulant clinic. Age, sex, comorbidities, number of daily medications, indication and type of anticoagulant, weekly dosage and distribution, were derived from electronic records. Differences by sex and regression analysis to identify significant modulators of TTR were computed.. 1182 women and 1281 men on VKA were studied. Women were older than men (81.5 yrs. ± 11.2 vs 78.4 yrs. ± 12.2), and had lower TTR (65% ± 20.3 vs 69% ± 19.8). Comorbidity was similar between sexes and negatively affected TTR in both. Mechanical valves as an indication to anticoagulation and acenocoumarol as an anticoagulant as opposed to warfarin had a strong negative influence on TTR, while age increased TTR. Being a man rather than a woman afforded more than three TTR points. Number of medications and average anticoagulant dose were equal between sexes.. Women have a lower TTR than men, on average below the safety threshold. They were indeed older, but age positively influenced TTR. Since women and men were equally comorbid, neither age nor disease explains differences in TTR. None of the other variables included in the study could explain the gender gap in TTR. Since women are at increased risk of cardioembolic stroke in atrial fibrillation, an effort at defining other causes for the observed differences, closer monitoring and switching to direct anticoagulants whenever possible is warranted.

Topics: Anticoagulants; Atrial Fibrillation; Comorbidity; Female; Humans; International Normalized Ratio; Male; Retrospective Studies; Stroke; Treatment Outcome; Vitamin K; Warfarin

The effectiveness of direct oral anticoagulants (DOAC) is non-inferior to vitamin K antagonists (VKA) to treat atrial fibrillation and venous thromboembolism (VTE). In this cross-sectional study, we compared older persons taking DOACs to those taking VKAs. We included ambulatory individuals ≥80 years, affiliated to Mutualité Sociale Agricole of Burgundy, who were refunded for a medical prescription in September 2017. The demographic conditions, registered chronic diseases (RCD), and number and types of prescribed drugs were compared in the DOAC group and VKA group. Of the 3190 included individuals, 1279 (40%) were prescribed DOACs and 1911 (60%) VKAs. Individuals taking VKAs were older than those taking DOACs (87.11 vs. 86.35 years). In the DOAC group, there were more women (51.92% vs. 48.25%) (

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; Venous Thromboembolism; Vitamin K

The oral anticoagulant dabigatran offers an effective alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), yet patient preference data are limited. The prospective observational RE-SONANCE study demonstrated that patients with AF, newly initiated on dabigatran, or switching to dabigatran from long-term VKA therapy, reported improved treatment convenience and satisfaction compared with VKA therapy. This pre-specified sub-study aimed to assess the impact of country and age on patients' perceptions of dabigatran or VKA therapy in AF.. RE-SONANCE was an observational, prospective, multi-national study (NCT02684981) that assessed treatment satisfaction and convenience in patients switching from VKAs to dabigatran (Cohort A), or newly diagnosed with AF receiving dabigatran or VKAs (Cohort B), using the PACT-Q questionnaire. Pre-specified exploratory outcomes: variation in PACT-Q2 scores by country and age (< 65, 65 to < 75, ≥ 75 years) (both cohorts); variation in PACT-Q1 responses at baseline by country and age (Cohort B).. Patients from 12 countries (Europe/Israel) were enrolled in Cohort A (n = 4103) or B (n = 5369). In Cohort A, mean (standard deviation) PACT-Q2 score increase was highest in Romania (convenience: 29.6 [23.6]) and Hungary (satisfaction: 26.0 [21.4]) (p < 0.001). In Cohort B, mean (standard error) increase in PACT-Q2 scores between dabigatran and VKAs was highest in Romania (visit 3: 29.0 [1.3]; 24.5 [0.9], p < 0.001). Mean PACT-Q2 score increase by age (all p < 0.001) was similar across ages. PACT-Q1 responses revealed lowest expectations of treatment success in Romania and greatest concerns about payment in Estonia, Latvia, and Romania, but were similar across ages.. Treatment satisfaction and convenience tended to favor dabigatran over VKAs. Regional differences in treatment expectations exist across Europe.. Trial registration number: ClinicalTrials.gov NCT02684981. Trial registration date: February 18, 2016.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Fibrinolytic Agents; Humans; Middle Aged; Prospective Studies; Stroke; Vitamin K

There are now anticoagulant choices with proposed advantages of non-vitamin K oral anticoagulants (NOACs) over warfarin being less routine monitoring and less drug interactions. Interacting medication can impact the efficacy and safety of anticoagulant therapy with management remaining clinically challenging. There have been limited studies comparing the potential for pharmacokinetic (PK) drug interactions between different anticoagulants. Therefore, the aim of this study was to compare potential PK interactions in patients with atrial fibrillation (AF) changing from warfarin to NOAC therapy. A retrospective analysis was conducted of patients with AF enrolled in a dedicated warfarin program but exiting this program to commence a NOAC. Patient data was collected, and concurrent medications were utilised to identify potential PK drug interactions with both warfarin and the chosen NOAC therapy. Patients were grouped according to the number of medications with potential PK interactions and comparisons made between groups. Of the 712 eligible patients who ceased warfarin to commence a NOAC, most commenced either apixaban (45.9%) or rivaroxaban (41.9%). When comparing warfarin to NOACs, there were significant differences in the proportion of patients taking no medication with potential PK drug interactions (46.9% vs 62.8%, p < 0.0001), and taking one (35.2% vs 28.5%, p = 0.0067) and two (14.5% vs 7.3%, p < 0.0001) potentially PK interacting medications. This study found when patients with AF were switched from warfarin to a NOAC, the potential for PK drug interactions significantly reduced but remained around 40%. Identifying and managing potential PK drug interactions with NOACs remains a priority to optimise clinical benefit of these anticoagulants.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Vitamin K; Warfarin

A very common side effect of non-vitamin K antagonist oral anticoagulant (NOAC) is (minor) bleeding. Data about impact and costs of minor bleeds in NOAC therapy is still limited or not present in current literature. In this patient orientated study, we aim to provide an estimate of the costs of minor bleeds in patients with atrial fibrillation (AF) treated with a NOAC.. A retrospective observational cohort study was conducted. Patients with AF and on NOAC therapy were included. Data was obtained by questionnaires and information from electronic patient records. Reference prices were used to calculate the costs per patient. Furthermore, cost of minor bleeds per patient is compared with literature-based costs of minor and major bleeding.. 139 patients were included. A total of 94 minor bleed were reported by 71 patients. The sum of minor bleeding costs from societal perspective were €9,851.49, or on average €70,87 (95% CI €54,37- €85,68) per patient with AF. The biggest cost drivers were rectal and vaginal bleeds, epistaxis was most commonly reported.. Total costs of minor bleeds from a societal perspective, in AF patients using NOACs, are non-trivial and exceed the costs presented in existing literature.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Retrospective Studies; Stroke; Vitamin K

The target ranges (TR) for anticoagulation with vitamin K antagonists (VKA) in the Netherlands were changed in 2016 from INR 2.0-3.5 ('low intensity') and INR 2.5-4.0 ('high intensity') to INR 2.0-3.0 and INR 2.5-3.5, respectively.. To assess the effect of the TR change on therapeutic quality control (TQC) in a Dutch regional thrombosis center taking care of approximately 3600-5500 patients annually.. TQC of chronically treated patients was assessed as the average time in therapeutic range (TTR). Evaluations were performed for non-self-management (NSM), as well as self-management patients. INR percentiles were assessed from all INR determinations in all patients, i.e. including those of induction episodes and patients treated for a short-term.. The number of NSM patients treated chronically decreased gradually, while their average age increased, with a marginal but significant gradual increase in bleeding complications. In the period 2011-2015, i.e. before the TR change, there was a gradual increase of the TTR in NSM patients from 77.5% to 88.9% (low intensity) and from 75.3% to 84.1% (high intensity). In the same period, the median INR of all patients in the low and high intensity ranges decreased from 2.9 to 2.7, and from 3.3 to 3.2, respectively. The TTR in self-management patients remained virtually constant. After TR changes from 2016 on, the TTR of all NSM patients in the low and high intensity groups decreased to 77% and 70%, respectively, and median INRs decreased to 2.6 and 3.0, respectively.. Introduction of internationally harmonized target ranges in 2016 resulted in further lowering of median INR values in both target ranges. As expected, TTR was reduced slightly. These findings, together with a slight increase in average age and concomitant bleeding complications, suggest that the patients on long-term VKA treatment will require intensified monitoring and treatment.

Topics: Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Netherlands; Quality Control; Thrombosis; Vitamin K

The aim of the present study is to identify a potential association of urinary tract infections (UTI) in a large population of patients receiving oral anticoagulation therapy treated in general practices in Germany. This study contains patients diagnosed with atrial fibrillation who received at least one prescription of either non-vitamin K antagonist oral anticoagulation (NOAC) or vitamin K antagonists (VKA) within January 2015 and December 2018. The incidence of UTI was examined cumulatively on the basis of Kaplan-Meier methods and was complemented by incidence rates measured in cases per 1000 patient years. Sex-stratified Cox regressions were conducted to examine possible associations in specific sex groups. The study comprised 26,934 patients receiving NOAC therapy and 8121 patients treated with VKA agents. Within a period of 5 years, slightly more NOAC than VKA users were diagnosed with UTI (20.3% vs. 19.3%), whereas the incidence rate was slightly higher in patients receiving NOAC therapy than in those under VKA treatment (50.8 cases vs. 50.5 cases in 1000 patient years). There was no significant association between direct oral anticoagulants versus vitamin K antagonists and infections of the urinary tract. Our study did not identify any significant association between therapy with direct oral anticoagulants versus vitamin K anticoagulants and UTI in patients diagnosed with atrial fibrillation in general practices in Germany. Because current findings regarding the risk of UTI in patients receiving oral anticoagulation therapy remain limited and contradictory, further investigations including a broad patient population are necessary to determine patients at risk for UTI and reconcile conflicting evidence.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Factor Xa Inhibitors; Female; Germany; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Urinary Tract Infections; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer.. In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups.. There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50–0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24–0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23–0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56–0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05).. Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Retrospective Studies; Stroke; Taiwan; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns.. A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors.. In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients.. Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Dabigatran; Female; Heart Disease Risk Factors; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Using French transcatheter aortic valve replacement (TAVR) registries linked with the nationwide administrative databases, the study compared the rates of long-term mortality, bleeding, and ischemic events after TAVR in patients requiring oral anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs).. The choice of optimal drug for anticoagulation after TAVR remains debated.. Data from the France-TAVI and FRANCE-2 registries were linked to the French national health single-payer claims database, from 2010 to 2017. Propensity score matching was used to reduce treatment-selection bias. Two primary endpoints were death from any cause (efficacy) and major bleeding (safety).. A total of 24,581 patients who underwent TAVR were included and 8,962 (36.4%) were treated with OAC. Among anticoagulated patients, 2,180 (24.3%) were on DOACs. After propensity matching, at 3 years, mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.12-1.67; P < 0.005) and major bleeding including hemorrhagic stroke (HR: 1.64; 95% CI: 1.17-2.29; P < 0.005) were lower in patients on DOACs compared with those on VKAs. The rates of ischemic stroke (HR: 1.32; 95% CI: 0.81-2.15; P = 0.27) and acute coronary syndrome (HR: 1.17; 95% CI: 0.68-1.99; P = 0.57) did not differ among groups.. In these large multicenter French TAVR registries with an exhaustive clinical follow-up, the long-term mortality and major bleeding were lower with DOACs than VKAs at discharge. The present study supports preferential use of DOACs rather than VKAs in patients requiring oral anticoagulation therapy after TAVR.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy is bleeding, and sometimes it can occur in unsuspected areas. Spontaneous pectoral hematoma is one of the rare complications due to over anticoagulation by VKA therapy, with only a few cases reported in the literature. Concomitant use of this therapy with commonly used antibiotic, especially in the elderly with multiple comorbidities, can increase the risk of bleeding. Herein, we report a case of a 72-year-old woman under VKA for the treatment of atrial fibrillation, who presented with a spontaneous massive pectoral hematoma, while using antibiotic to treat a respiratory tract infection, who was successfully managed.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Female; Hematoma; Hemorrhage; Humans; Thromboembolism; Vitamin K

Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce.. Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders.. We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio [HR], 0.58 [95% CI, 0.42–0.81]), as did independent compared to dependent patients (HR, 0.54 [95% CI, 0.40–0.71]). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HRdependent, 0.68 [95% CI, 0.45–1.01]) and independent patients (HRindependent, 0.44 [95% CI, 0.26–0.75]) in the simple model (Pinteraction=0.212). Adjusted (HRdependent, 0.74 [95% CI, 0.49–1.11] and HRindependent, 0.51 [95% CI, 0.30–0.87]; Pinteraction=0.284) and weighted models (HRdependent, 0.79 [95% CI, 0.48–1.31] and HRindependent, 0.46 [95% CI, 0.26–0.81]; Pinteraction=0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses.. The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge.. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03826927.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Recurrence; Secondary Prevention; Stroke; Treatment Outcome; Vitamin K

Uninterrupted direct oral anticoagulation (DOAC) in AF-ablation is recommended, proven by randomized trials. The outcome and the periinterventional differences between DOACs and VKA in the real world clinical practice are discussed controversial.. To investigate efficiency and safety of uninterrupted DOAC therapy compared to VKA during AF-Ablation in real world setting with a focus on periinterventional heparin dosage.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Vitamin K; Vitamins

The coronavirus pandemic disease 2019 (COVID-19) has changed the face of contemporary medicine. However, each and every medical practitioner must be aware of potential early and late complications of COVID-19, its impact on chronic diseases - especially ones as common as atrial fibrillation (AF) - and the possible interactions between patients' chronic medications and pharmacotherapy of COVID-19. Patients with AF due to comorbidities and, often, elderly age are assumed to be at a higher risk of a severe course of COVID-19. This expert consensus summarizes the current knowledge regarding the pharmacotherapy of AF patients in the setting of the COVID-19 pandemic. In general, anticoagulation principles in quarantined or asymptomatic individuals remain unchanged. Nevertheless, it is advisable to switch from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants (NOACs) whenever possible due to their consistent benefits and safety with fixed dosing and no monitoring. Additionally, in AF patients hospitalized due to mild or moderate COVID-19 pneumonia, we recommend continuing NOAC treatment or to switching to low-molecular-weight heparin (LMWH). On the other hand, in severely ill patients hospitalized in intensive care units, intravenous or subcutaneous dosing is preferable to oral, which is why the treatment of choice is either LMWH or unfractionated heparin. Finally, particularly in critical scenarios, the treatment strategy in COVID-19 patients with AF should be individualized based on possible interactions between anticoagulants, antiarrhythmics, antivirals, and antibiotics. In this consensus, we also discuss how to safely perform COVID-19 vaccination in anticoagulated AF patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; COVID-19; COVID-19 Vaccines; Heparin; Heparin, Low-Molecular-Weight; Humans; Pandemics; SARS-CoV-2; Stroke; Vitamin K

To analyze the use, effectiveness, safety and costs of stroke prevention in non-valvular atrial fibrillation (AF) in patients initiating treatment with dabigatran or vitamin K antagonists (VKA).. Primary Care (PC) at the Catalan Health Institute (ICS) in Catalonia, during 2011-2013.. Patients attended in ICS PC centres with a registered diagnosis of AF who initiate dabigatran or VKA.. Not applicable MAIN MEASUREMENTS: Number of prescriptions and reimbursements of dabigatran and VKA, incidence of stroke and haemorrhages, incidence of mortatlity, number of sickness leave, and costs associated to all the previous variables.. 14,930 patients were included; 94.6% initiated VKA and 5.4%, dabigatran. Dabigatran patients were younger and with less comorbidity. There were no statistically significant differences between VKA and dabigatran in the risk of stroke, haemorrhages or death. The costs associated to AF management were higher for PC visits in the VKA group, and higher for laboratory and pharmacy in the dabigatran group, although overall costs were not statistically different.. Most patients initiated VKA. We found no differences between VKA and dabigatran in the risk of stroke, haemorrhages or mortality.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Cohort Studies; Costs and Cost Analysis; Dabigatran; Female; Hemorrhage; Hospitalization; Humans; Incidence; Male; Middle Aged; Primary Health Care; Propensity Score; Stroke; Thromboembolism; Vitamin K

The real-life benefits and risks of the non-vitamin K antagonist oral anticoagulants for stroke prevention in very elderly patients with atrial fibrillation (AF) are still debated.. Cohorts of new users of rivaroxaban 15 mg, dabigatran 110 mg, or vitamin K antagonists (VKA) for AF ≥85 years old in 2013 or 2014 were identified in the nationwide French claims database and followed-up for 1 year. Cohorts were compared after 1:1 matching using high-dimensional propensity score. Compared to VKA use and considering 1-year cumulative incidences, risk of stroke, and systemic embolism was not different with rivaroxaban use [hazard ratio 1.14, 95% confidence interval (CI): 0.93-1.40] and lower with dabigatran use (0.77, 95% CI: 0.60-0.99), risk of major bleeding was not different with rivaroxaban use (0.91, 95% CI: 0.74-1.11) and with dabigatran use (0.81, 95% CI: 0.64-1.03), risk of all-cause death was borderline to significance lower with rivaroxaban use (0.91, 95% CI: 0.83-1.00), and lower with dabigatran use (0.87, 95% CI: 0.78-0.97). The risk for a composite of all events above was not different with rivaroxaban use (0.96, 95% CI: 0.88-1.04) and lower with dabigatran use (0.87, 95% CI: 0.79-0.96) as compared with VKA use. The risk for the composite of all events was not different with rivaroxaban use as compared with dabigatran use (1.09, 95% CI: 0.97-1.23).. This study shows for the first time in more than 25 000 new real-life anticoagulant users for AF aged ≥85 years a neutral overall benefit-risk of rivaroxaban 15 mg vs. VKA and a favourable overall benefit-risk of dabigatran 110 mg vs. VKA on relevant clinical events.. European Medicines Agency EUPAS14567 (www.encepp.eu) and Clinicaltrials.gov id NCT02864758.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Humans; Rivaroxaban; Stroke; Vitamin K

Empirically, a significant proportion of patients using direct oral anticoagulation (DOAC) take off-label reduced doses. We aimed to investigate the prevalence, indications, dosages, and bleeding complications of oral anticoagulants on admission to the emergency department.. In this retrospective analysis, patients presenting to our emergency department between January 1 and December 31, 2018, with therapeutic oral anticoagulation were included (ie, vitamin-K antagonists, rivaroxaban, apixaban, edoxaban, and dabigatran). A detailed chart review was performed for each case concerning characteristics, indication, and bleeding complications.. A total of 19,662 consecutive cases in the emergency department were reported: 1721 (9%) had therapeutic oral anticoagulation. Vitamin-K antagonists (41%), rivaroxaban (36%), and apixaban (19%) were the most common. Stroke prophylaxis in patients with atrial fibrillation (63.2%) and venous thromboembolism (24.1%) were the most common indications. In 27 cases (1.6%), no indication could be identified; further, 32% of patients were classified to have either off-label doses of DOACs or an international normalized ratio (INR) out of range (in vitamin-K antagonists), whereas 20% were classified as off-label underdosed and 12% as overdosed. No difference in the likelihood of bleeding on admission could be found between the respective drugs. Only concomitant use of aspirin was significantly associated with presence and higher severity of bleeding.. Vitamin-K antagonists are still the most widely used drug followed by rivaroxaban. A significant proportion of patients are being prescribed off label-doses. While no difference was found for the respective anticoagulants with respect to bleeding, concomitant aspirin use was a significant predictor for bleeding in our collective.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Emergency Service, Hospital; Female; Hemorrhage; Humans; Male; Off-Label Use; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Thiazoles; Vitamin K

Warfarin is deemed safe compared to bridging with heparin in the peri-procedure setting while implanting cardiac devices. The timing of discontinuation and re-initiation of direct anticoagulant agents (DOACs) such as dabigatran, apixaban, and rivaroxaban in the peri-procedural setting in comparison to warfarin is not well studied.. We wanted to compare three DOAC agents with warfarin during cardiac device implantation.. Consecutive patients on treatment with dabigatran, rivaroxaban, or apixaban (group A) undergoing a cardiac device generator change, upgrade, or new implantation procedure were compared to those on warfarin (group B). Incidence of hematoma, infection, effusion, stroke, and other complications were noted at 1 day, 1 week, and 3 months.. A total of 311 patients in group A underwent the above procedures with 73 patients on dabigatran, 153 on rivaroxaban, and 85 on apixaban. There were 467 patients on warfarin in group B. Mean age of the total population was 68 ± 12 years with 67% males and > 80% Caucasians. The last dose of the DOAC was the night prior to the procedure and resumed the night of the procedure (single dose interruption for apixaban and dabigatran and no un-interruption for rivaroxaban). There was no difference noted in the incidence of minor or major hematoma (9% vs 8.5%, p = 0.7). No stroke occurred in either group.. Use of DOAC agents with transient interruption of one dose is as safe as warfarin in the peri-procedural setting during implantation of cardiac devices.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Defibrillators, Implantable; Female; Humans; Male; Middle Aged; Pyridones; Rivaroxaban; Vitamin K; Warfarin

Nonagenarian patients are underrepresented in clinical trials that have evaluated oral anticoagulation in patients with atrial fibrillation (AF). The aim of this study was to assess the pronostic impact of oral anticoagulation in patients with AF age ≥90 years.. Retrospective multicenter study of nonagenarian patients with AF.. A total of 1750 nonagenarian inpatients and outpatients with nonvalvular AF between January 2013 and December 2018 in 3 Spanish health areas were studied.. Patients were divided into 3 groups based on antithrombotic therapy: nonoral anticoagulants (30.5%), vitamin-K antagonists (VKAs; 28.6%), and direct oral anticoagulants (DOACs; 40.9%). During a mean follow-up of 23.6 ± 6.6 months, efficacy outcomes (death and embolic events) were evaluated using a Cox regression analysis and safety outcomes (bleeding requiring hospitalization) by competing-risk regression. Results were complemented with a propensity score matching analysis.. During follow-up, 988 patients died (56.5%), 180 had embolic events (10.3%), and 186 had major bleeding (10.6%). After multivariable adjustment, DOACs were associated with a lower risk of death and embolic events than nonanticoagulation [hazard ratio (HR) 0.75, 95% confidence interval (CI)] 0.61‒0.92), but VKAs were not (HR 0.87, 95% CI 0.72‒1.05). These results were confirmed after propensity score matching analysis. For bleeding, both DOACs and VKAs proved to be associated with a higher risk (HR for DOAC 1.43; 95% CI 0.97‒2.13; HR for VKA 1.94; 95% CI 1.31‒2.88), although findings for DOACs were not statistically significant (P = .074). For intracranial hemorrhage (ICH), only VKAs-not DOACs-presented a higher risk of ICH (HR 4.43; 95% CI 1.48‒13.31).. In nonagenarian patients with AF, DOACs led to a reduction in mortality and embolic events in comparison with nonanticoagulation. This reduction was not observed with VKAs. Although both DOACs and VKAs increased the risk of bleeding, only VKAs were associated with higher ICH rates.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Retrospective Studies; Stroke; Vitamin K

Administrative data were used to investigate changes in hospitalizations for atrial fibrillation (AF), AF-related stroke, and treatment patterns between 2012 and 2016.. From the 'Ricerca e Salute' database, a population- and patient-based repository involving >12 million inhabitants and linking demographics, prescriptions, and hospital discharge records, all patients discharged alive with a diagnosis of AF between 2012 and 2015 were followed for 1 year.. A total of 194,030 AF patients were included. The number of AF cases increased ~10% over time, from 4.0 per 1,000 inhabitants in 2012 to 4.4 per 1,000 in 2015. At 1 year, hospitalizations for ischemic stroke decreased from 21.3 per 1,000 patients with AF in 2012-2013 to 14.7 per 1,000 in 2015-2016 (-31%, 95% CI -18 to -41). Over the same period, oral anticoagulant (OAC) use increased from 56.7% to 64.4% (+14%, 95% CI +8 to +26), vitamin K antagonist use decreased (from 55.9 to 36.7%; -34%, 95% CI -21 to -44), whereas direct OACs (DOACs) increased (from <1% in 2012 to 27.7% in 2015). Antiplatelet prescriptions fell from 42.6% in 2012 to 28.1% in 2015. Hospitalizations for major bleeds, mainly gastrointestinal, increased from 1.5‰ in 2012-2013 to 2.3‰ in 2015-2016, whereas hemorrhagic stroke admissions decreased from 6.5‰ to 4.1‰.. There was a slight increase in the prevalence of AF between 2012 and 2015, whereas the overall use of antiplatelet agents decreased and that of OAC, particularly DOACs, increased. Over the same period, 1-year hospitalizations for ischemic stroke declined substantially, with a declining rate of hemorrhagic strokes.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catchment Area, Health; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Health Expenditures; Hemorrhage; Hospitalization; Humans; Italy; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Stroke; Time Factors; Vitamin K

The Time in Therapeutic Range (TTR) is the gold-standard measure used to assess the quality of oral anticoagulation with vitamin K antagonists. However, TTR is a static measure, and International Normalized Ratio (INR) control is a dynamic process. Group-based Trajectory Models (GBTM) can address this dynamic nature by classifying patients into different trajectories of INR control over time.. The objective of this study was to assess the quality of INR control in a population-based cohort of new users of vitamin K antagonist with a diagnosis of atrial fibrillation using GBTM.. We classified patients into different trajectories according to their propensity for being adequately anticoagulated over their first year of treatment using GBTM, and we evaluated the association between trajectories and relevant clinical outcomes over the following year.. We included 8024 patients in the cohort who fulfilled the inclusion criteria; the mean number of INR determinations over the first year of treatment was 13.9. We identified 4 differential trajectories of INR control: Optimal (9.7% of patients, TTR: 83.8%), Improving (27.4% of patients, TTR: 61.2%), Worsening (28%; TTR: 69.1%), and Poor control (34.9%; TTR: 41.5%). In adjusted analysis, Poor and Worsening control patients had a higher risk of death than Optimal control patients (hazard ratio: 1.79; IC 95%, 1.36-2.36 and hazard ratio: 1.36; IC 95%, 1.02-1.81, respectively). Differences in other outcomes did not achieve statistical significance, except for a reduced risk of transient ischemic attack in the Improving Control group.. GBTM may contribute to a better understanding and assessment of the quality of oral anticoagulation and may be used in addition to traditional, well-established measures such as TTR.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Male; Middle Aged; Spain; Vitamin K

Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment.. Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0-30 after starting treatment and clinical outcomes over days 31-365 in a derivation cohort (cohorts 1-3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4-5; n = 1523). The model's c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively.. Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Databases, Factual; Drug Monitoring; Drug Therapy, Computer-Assisted; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Neural Networks, Computer; Predictive Value of Tests; Prospective Studies; Prothrombin Time; Registries; Reproducibility of Results; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

A significant number of patients with non-valvular atrial fibrillation (NVAF) are ineligible for non-vitamin K oral anticoagulants (NOACs) due to previous major bleeding or because they are at high bleeding risk (HBR). In this setting the indication for percutaneous left atrial appendage closure (LAAO) is a valuable alternative. We aimed to evaluate the efficacy and safety of NOACs versus LAAO indication in NVAF patients at HBR (HAS-BLED ≥3).. All consecutive patients who underwent successful LAAO (n=193) and those treated with NOACs (n=189) (dabigatran, apixaban or rivaroxaban) were included. A 1:1 propensity score matching (PSM) was used to match LAAO and NOACs patients. At baseline, patients in the LAAO group had higher HAS-BLED (4.2% vs 3.3%, p<0.001) and lower CHADS-VASc (4.3% vs 4.7%, p=0.005) scores. After 1:1 PSM, 192 patients were enrolled in the final analysis (LAAO n=96; NOACs n=96). At two-year follow-up, no significant differences in thromboembolic (7.3% vs 6.3%, p=0.966) and ISTH major bleeding event rates (6.7% vs 4.8% p=0.503) were found between the two unmatched groups. All-cause death was significantly higher in the LAAO group (18.7% vs 10.6%; p=0.049). After PSM, all-cause death, thromboembolic and ISTH major bleeding event rates were similar between the groups. Significant independent predictors of all-cause death were dialysis (HR 5.65, 95% CI: 2.16-14.85, p<0.001) and age (HR 1.08, 95% CI: 1.05-1.13, p<0.001).. In NVAF patients at HBR, LAAO and NOACs performed similarly in terms of thromboembolic and major bleeding events up to two-year follow-up. Our findings warrant further investigation in randomised trials and therefore can be considered as hypothesis-generating.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Comparative Effectiveness Research; Hemorrhage; Humans; Pyridones; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cardiologists; Female; Humans; Male; Perception; Spain; Stroke; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Humans; Prejudice; Rivaroxaban; Stroke; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Drug Administration Schedule; Female; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; United Kingdom; Vitamin K

 The benefit of periprocedural bridging with low-molecular-weight heparin (LMWH) in patients with atrial fibrillation has been contested by the publication of the BRIDGE trial..  This article determines whether publication of the BRIDGE trial has led to less bridging procedures and better patient outcomes (i.e., a composite of thromboembolism, major bleeding, and death) in patients undergoing invasive procedures at the Leiden Anticoagulation Clinic, the Netherlands..  We identified all procedures that required vitamin K antagonist interruption. Procedures were divided in a period before (2014-2016; 22 months) and after the publication of the BRIDGE trial (2016-2017; 22 months). Cumulative incidences 30 days postprocedure and relative risks of thromboembolic events, major bleeding, and mortality were calculated..  A total of 4,892 and 4,237 eligible procedures were performed in 2014 to 2016 and 2016 to 2017, respectively. The cumulative incidence of thromboembolism was 0.5% in 2014 to 2016 compared with 0.3% in 2016 to 2017; adjusted odds ratio (OR) 0.60 (95% confidence interval [CI] 0.30-1.21). The cumulative incidence of major bleeding was 1.0% in the 2014 to 2016 period as compared with 1.3% in the 2016 to 2017 period; adjusted OR was 1.27 (95% CI 0.85-1.90). The adjusted OR of the composite endpoint was 1.05 (95% CI 0.74-1.48). The frequency of bridging with LMWH (14.8% in 2014-2016 vs. 16.6% in 2016-2017) as well as mean CHA.  We showed that despite publication of the BRIDGE trial, the frequency of bridging with LMWH and patient outcomes regarding bleeding complications did not change.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Male; Netherlands; Odds Ratio; Perioperative Period; Practice Guidelines as Topic; Risk; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

It has been reported that oral anticoagulation (OAC) is underused among Chinese patients with non-valvular atrial fibrillation (NVAF). Non-vitamin K antagonist oral anticoagulants (NOAC) have been recommended by recent guidelines and have been covered since 2017 by the Chinese medical insurance; thus, the overall situation of anticoagulant therapy may change. The aim of this study was to explore the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province.. This was a multi-center, cross-sectional study that was conducted in seven hospitals from January to September in 2017. The demographic characteristics and medical history of the patients were collected by questionnaire and from the medical records. Multivariate logistic regression was used to identify factors associated with anticoagulant therapy.. A total of 593 patients were included in the analysis. A total of 35.6% of the participants received OAC (11.1% NOAC and 24.5% warfarin). Of those patients with a high risk of stroke, 11.1% were on NOAC, 24.8% on warfarin, 30.6% on aspirin, and 33.6% were not on medication. Self-paying, duration of AF ≥5 years were negatively associated with anticoagulant therapy in all patients (OR 1.724, 95% CI 1.086~2.794; OR 1.471, 95% CI 1.006~2.149, respectively), whereas, permanent AF was positively associated with anticoagulant therapy (OR 0.424, 95% CI 0.215~0.839). Among patients with high risk of stroke, self-paying and increasing age were negatively associated with anticoagulant therapy (OR 2.305, 95% CI 1.186~4.478; OR 1.087, 95% CI 1.041~1.135, respectively).. Anticoagulant therapy is positively associated with permanent AF and negatively associated with self-paying, duration of AF > 5 years. Furthermore, the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province does not appear optimistic. Therefore, further studies should focus on how to improve the rate of OAC use among NVAF patients. In addition, policy makers should pay attention to the economic situation of the patients with NVAF using NOAC.. 2,017,029. Registered 20 March 2017 (retrospectively registered).

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; China; Cross-Sectional Studies; Drug Costs; Drug Utilization; Factor Xa Inhibitors; Female; Health Expenditures; Humans; Male; Medication Adherence; Middle Aged; Practice Patterns, Physicians'; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Atrial fibrillation is the most common sustained arrhythmia in the general population, and circumferential pulmonary vein isolation has emerged as a cornerstone in the treatment of drug-resistant atrial fibrillation. However, there is a paucity of data regarding the CHA2DS2-VASc and SAMe-TT2R2 scores as predictors of outcomes among patients with nonvalvular atrial fibrillation on vitamin K antagonists after radiofrequency catheter ablation (RFCA).. The current prospective observational study enrolled 304 consecutive patients with atrial fibrillation who underwent RFCA. Warfarin was maintained for at least 3 months after RFCA. The 1-year atrial fibrillation recurrence rate was documented.. Persistent atrial fibrillation (P = 0.003), heart failure (P < 0.001), an enlarged left atrium (P = 0.003), current smoking (P < 0.001), the CHA2DS2-VASc score (P = 0.001), and the SAMe-TT2R2 score (P < 0.001) were univariate associated with recurrent atrial fibrillation. Cutoff analysis showed that a CHA2DS2-VASc score at least 3 (areas under the curve = 0.612; 95% confidence interval 0.537-0.687) and a SAMe-TT2R2 score at least 5 (areas under the curve = 0.642, 95% confidence interval 0.575-0.708) had the highest predictive value for atrial fibrillation recurrence. Patients with a CHA2DS2-VASc score at least 3 (P < 0.001) and a SAMe-TT2R2 score at least 5 (P = 0.001) had a higher probability of experiencing atrial fibrillation recurrence after RFCA compared with patients with a CHA2DS2-VASc score less than 3 and a SAMe-TT2R2 score less than 5.. CHA2DS2-VASc and SAMe-TT2R2 scores were associated with 1-year recurrence of atrial fibrillation in patients on vitamin K antagonists after RFCA. For CHA2DS2-VASc and SAMe-TT2R2 scores, a cutoff value of at least 3 and at least 5 had the highest predictive value for atrial fibrillation recurrence, respectively.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Decision Support Techniques; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Pulmonary Veins; Recurrence; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Anticoagulant therapy in patients with atrial fibrillation (AF) increases the risk of minor bleeding, which is mostly accepted by patients. We aimed to assess whether continuation of anticoagulation despite minor bleeding is associated with a higher level of knowledge on AF and anticoagulation.. In 1525 patients with AF on oral anticoagulation who completed the Jessa AF Knowledge Questionnaire (JAKQ) (median age: 72 years [range, 65-79 years]; men: 54.6%), persistent self-reported minor bleeding was recorded. Minor bleeding was observed in 567 patients (37.2%) including 224 patients (39.5%) on vitamin K antagonists (VKAs) and 343 (60.5%) on non-vitamin K antagonist oral anticoagulants (NOACs). The risk of minor bleeding was lower among patients on NOACs than on VKAs (33.5% vs 44.6%; P < .0001). Multiple logistic regression showed that minor bleeding was associated with the use of NOACs (odds ratio [OR] 0.75; 95% CI 0.59-0.97), female gender (OR 2.19; 95% CI, 1.74-2.75; P < .0001), history of major bleeding (OR 2.85; 95% CI, 1.96-4.14; P < .0001), time since AF diagnosis (OR 1.04; 95% CI, 1.01-1.06; P < .0001), concomitant vascular disease (OR 1.43; 95% CI, 1.10-1.87; P = .0008) and diabetes mellitus (OR 1.3; 95% CI, 1.02-1.65, P = .03). Patients with minor bleeding, compared with the remaining subjects scored higher on the JAKQ (median, 62.5% vs 56.2%, respectively, P < .0001). The former group knew more about the purpose of anticoagulant therapy (71.8% vs 65.7%, P = .01) and bleeding as its key side effect (66.1% vs 52.7%, P < .0001), and were better informed on the safest painkillers to use in combination with anticoagulation (48% vs 35%, P < .0001).. This study suggests that AF patients who accept persistent minor bleeding have better knowledge on the disease and anticoagulation therapy compared with those free of these side effects.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Health Knowledge, Attitudes, Practice; Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Stroke; Surveys and Questionnaires; Vitamin K

Oral anticoagulation therapy is frequently prescribed to kidney transplant recipients (KTRs) for prevention and treatment of thrombotic events. Over the past 10 y, direct oral anticoagulants (DOACs) have shown similar efficacy with a safety profile equal or superior to that of vitamin K antagonist anticoagulants (VKAs) in the general population. However, little data are available on kidney transplantation.. We investigated the efficacy (thrombotic events) and safety (hemorrhagic and other adverse events and graft outcomes) of DOACs in a cohort of KTRs with a renal function >30 mL/min. We then compared these patients to a control group treated by VKA.. Fifty-two KTRs treated by DOACs between 2013 and 2018 at Necker Hospital were included. Patients were with a mean age of 62 ± 13 y old and a mean glomerular filtration rate of 59 ± 20 mL/min/1.73m. The major indication was atrial fibrillation (n = 31 [60%]). Apixaban was the most commonly used agent (n = 36 [69%]). No thrombotic complications were reported under DOAC until last follow-up (14.1 ± 13 mo). In comparison to 50 controls under VKA during the same period, the bleeding rate under DOAC was significantly lower (11.5 versus 22.9 per 100 patient-y, P = 0.037) with a hazard ratio of 0.39 (95% confidence interval, 0.19-0.85, P = 0.041). No significant changes in kidney function, rejection rate, or hemoglobin level were reported.. DOACs appear to be effective and safe anticoagulants in KTRs with stable renal function.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Factor Xa Inhibitors; Female; Graft Survival; Hemorrhage; Humans; Kidney Transplantation; Male; Middle Aged; Patient Safety; Pilot Projects; Retrospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Treatment Outcome; Vitamin K

Acute ischemic stroke (AIS) severity and clinical course are less known in direct oral anticoagulants (DOAC) users. We aimed to explore the outcome of AIS in patients pretreated with vitamin-K-antagonists (VKA) and DOAC.. A retrospective study was performed. Patients pretreated with oral anticoagulants (OAC) for nonvalvular atrial fibrillation admitted for AIS in a stroke unit between 2016-01-01 and 2018-08-31 were included. The primary endpoint was mortality during the hospital stay, and secondary endpoints were neurologic improvement at stroke unit discharge and good functional outcome 90 days after AIS.. A total of 156 patients were included (83 on VKA and 73 on DOAC). Stroke severity (defined by NIHSS on admission) was comparable in both groups (AVK 13.0 [4.0-20.0] versus DOAC 11.0 [4.0-17.0], P = .435). Infratherapeutic levels and/or inappropriate low dose of OAC was also similar between groups (P = .152) and was not associated with stroke severity (P = .631) or mortality (P = .788). VKA (OR 12.616, P = .035, 95%CI 1.19-133.64) and PH2 hemorrhagic transformation (OR 7.516, P = .024, 95%CI 1.31-43.20) were associated with higher mortality in multivariate analysis. Higher stroke severity (OR .101, P < .001, 95%CI .037-.279) and VKA usage (OR .212, P = .003, 95%CI .08-.58) were associated with worse functional outcome at 3 months. Reperfusion therapy was significantly associated with neurologic improvement during stroke unit stay (OR 3.969, P = .009, 95%CI 1.42-11.11) but not with the functional outcome (P = .063).. Nonvalvular atrial fibrillation patients pretreated with DOAC admitted for AIS had a better outcome when compared to VKA, although stroke severity was similar between groups.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Brain Ischemia; Disability Evaluation; Female; Hospital Mortality; Humans; Male; Recovery of Function; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; Osteoporotic Fractures; Vitamin K

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K; Warfarin

Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed dose, the few interactions and less frequent controls, have made them the first choice anticoagulant therapy. More and more patients have therefore switched from therapy with vitamin K antagonists (VKAs) to DOACs. Aim of our study was to assess the satisfaction, quality of life (QoL) and therapy adherence of patients who switched from VKA to DOACs therapy. This single center study evaluated satisfaction and QoL of 107 patients who switched from VKA to DOACs therapy through Anti-Clot Treatment Scale and SF-36 respectively. The questionnaires were administered before therapy change, after 3 months of DOACs therapy and then annually. We also evaluated DOACs therapy adherence with a questionnaire administered each visit and through the measures of DOACs plasma levels. Patients' satisfaction and QoL were high during VKA therapy, but with DOACs we observed an improvement after the first 3 months and then maintained over the time of DOACs therapy. DOACs adherence was excellent, also confirmed by DOACs plasma levels.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Patient Compliance; Patient Satisfaction; Quality of Life; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo.. In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y. Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23-1.70]) and fewer severe ischemic events (absolute risk difference, -0.91% [95% CI, -1.74 to -0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23-2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, -0.17% [95% CI, -1.33 to 0.98]).

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Thrombosis; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs).. A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received.. Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%,. In this "real-world" registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.

Topics: Administration, Oral; Age Factors; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Prospective Studies; Registries; Risk Assessment; Risk Factors; Spain; Stroke; Time Factors; Treatment Outcome; Vitamin K

We evaluated atrial fibrillation (AF) patients' perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications.. The RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30-45 and 150-210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3.. The main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p<0.001 for all) for treatment convenience (mean change V1 vs V2=20.72; SD=21.50; V1 vs V3=24.54; SD=22.85) and treatment satisfaction (mean change V1 vs V2=17.60; SD=18.76; V1 vs V3=21.04; SD=20.24). In cohort B, mean PACT-Q2 scores at V2 and V3 were significantly higher (p<0.001 for all) for dabigatran versus a VKA for treatment convenience (V2=18.38; SE =0.51; V3=23.34; SE=0.51) and satisfaction (V2=15.88; SE=0.39; V3=19.01; SE=0.41).. Switching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Drug Substitution; Europe; Female; Health Knowledge, Attitudes, Practice; Hemorrhage; Humans; Israel; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Protective Factors; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Young Adult

Oral anticoagulants are the first-line drugs for treating thrombotic disorders related to nonvalvular atrial fibrillation and for treating deep vein thrombosis, diseases that increase in prevalence with age. Older patients have a greater risk of thrombotic and hemorrhagic events and are more prone to drug interactions. Given this backdrop, we wanted to determine the factors associated with the prescription of direct oral anticoagulants and vitamin K antagonists in older patients.. We performed a cross-sectional observational study using a hospital prescription database. The study population consists of 405 older patients who were given oral anticoagulants. The 2 variables of interest were the prescription of 1 of the 2 classes of oral anticoagulants (direct oral anticoagulants vs vitamin K antagonists) and appropriateness of oral anticoagulant prescribing according to Summary of Product Characteristics (potentially inappropriate vs appropriate).. The factors associated with direct oral anticoagulant prescribing were the female gender (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.22-2.88) and initiation during hospital stay (OR: 2.56, 95% CI: [1.52-4.32]). Stage 4 and 5 chronic kidney diseases (OR: 0.39, 95% CI: [0.19-0.79] and OR: 0.07, 95% CI: [0.01-0.53]) were factors favoring vitamin K antagonist prescription. Being 90 years of age or more (OR: 2.05, 95% CI: [1.06-3.98]) was a factor for potentially inappropriate anticoagulant prescribing. The gastroenterology department (OR: 2.91, 95% CI: [1.05-8.11]) was associated with potentially inappropriate anticoagulant prescribing.. Direct oral anticoagulants are the drugs of choice for anticoagulant treatment, including in older adults. The female gender and the initiation during hospital stay increased the chances of being prescribed a direct oral anticoagulant in older adults. Stage 4 and 5 chronic kidney disease increased the likelihood of having a vitamin K antagonist prescribed. Our study also revealed a persistence of potentially inappropriate oral anticoagulant prescriptions in older patients.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Cross-Sectional Studies; Databases, Factual; Drug Interactions; Factor Xa Inhibitors; Female; France; Hemorrhage; Humans; Inappropriate Prescribing; Male; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

The evolution of non-vitamin K antagonist anticoagulants (NOACs) has changed the horizon of stroke prevention in atrial fibrillation (SPAF). All 4 NOACs have been tested against dose-adjusted warfarin in well-designed, pivotal, phase III, randomized, controlled trials (RCTs) and were approved by regulatory authorities for an SPAF indication. However, as traditional RCTs, these trials have important weaknesses, largely related to their complex structure and patient participation, which was limited by strict inclusion and extensive exclusion criteria. In the real world, however, clinicians are often faced with complex, multimorbid patients who are underrepresented in these RCTs. This article is based on a meeting report authored by 12 scientists studying atrial fibrillation (AF) in diverse ways who discussed the management of challenging AF cases that are underrepresented in pivotal NOAC trials.. An advisory board panel was convened to confer on management strategies for challenging AF cases. The article is derived from a summary of case presentations and the collaborative discussions at the meeting.. This expert consensus of cardiologists aimed to define management strategies for challenging cases with patients who underrepresented in pivotal trials using case examples from their routine practice. Although strong evidence is lacking, exploratory subgroup analysis of phase III pivotal trials partially informs the management of these patients. Clinical trials with higher external validity are needed to clarify areas of uncertainty. The lack of clear evidence about complex AF cases has pushed clinicians to manage patients based on clinical experience, including rare situations of off-label prescriptions.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiologists; Clinical Trials, Phase III as Topic; Consensus; Dabigatran; Disease Management; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiazoles; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

The main objective of our study was to carry out a statement of the knowledge and the management of the VKA by the General Practitioners (GPs) of Normandy and to evaluate their experience of the use of DOA with a questionnaire; 471 of the 1951 GPs requested responded. When the INR was stable in a patient affected with atrial fibrillation, the GPs participating dosed it again 4 weeks later, modified the dosage when the INR was below 1.9 or upper 3.2. The risk of stroke was overestimated to 6.2% per year with fluindione and to 31.5% without curative anticoagulation. The mean TTR was overstated to 84%. When the INR was at 4.4, the risk of serious cerebral bleeding was overestimated at 12.4%. 80.26% of the GPs skipped the next dose and 11.25% controlled the INR the day after. So, few GPs used the HAS protocol. After the INR decreased to 3.6, the GPs diminished the dose of 14.62%. 70% of the GPs, responded using only their experience for AVK management. Fluindione was the most to use VKA by 52.7% of them although 24.42% thought it was the most effective. The majority of GPs thought the DOA were a least as effective than the VKA, without being responsible of more bleeding (77.92%) and improved the quality of life of the patients (88.54%). Although the DOA's prescriptions increase, the improvement of the VKA management have to stay a concern for the GPs.

Topics: 4-Hydroxycoumarins; Adult; Atrial Fibrillation; Blood Coagulation; Cross-Sectional Studies; Female; France; Guideline Adherence; Health Knowledge, Attitudes, Practice; Humans; Indenes; International Normalized Ratio; Male; Middle Aged; Monitoring, Physiologic; Physicians, Primary Care; Practice Patterns, Physicians'; Surveys and Questionnaires; Vitamin K

To assess the safety (ie, risk of bleeding) and effectiveness (ie, risk of stroke/systemic embolism (SE)) separately for four non-vitamin K oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) versus warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF), including those at high risk of bleeding and treated with reduced doses of NOACs.. We conducted a retrospective analysis of electronic health records and claims data from 372 acute care hospitals in Japan for patients with NVAF newly initiated on NOACs or warfarin. Baseline characteristics were balanced using inverse probability of treatment weighting with stabilised weights (s-IPTW). Bleeding risk and stroke/SE risk were expressed as HRs with 95% CIs. Two sensitivity analyses were conducted.. In patients with NVAF primarily treated with reduced-dose NOACs, the risks of stroke/SE and major bleeding were significantly lower with NOACs versus warfarin.

Topics: Administration, Oral; Administrative Claims, Healthcare; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Electronic Health Records; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Patient Safety; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Time Factors; Treatment Outcome; Vitamin K; Warfarin

To compare mortality between anticoagulated atrial fibrillation patients and general population and among anticoagulation specific categories [direct oral anticoagulants (DOACs) vs. vitamin K antagonists(VKA)].. This was a population-based study including all residents in the Veneto Region aged 18 years or older. Administrative claims from July 2013 to September 2017 were used to identify anticoagulation-naïve atrial fibrillation patients. Propensity score matching was employed to compare patients on new and old anticoagulants.. Overall, 17 225 patients on direct anticoagulants were 1 : 1 matched to patients on VKA (49% males, median age 77 years). Mortality was higher with respect to the general population by 22 and 39% among patients on direct anticoagulants and VKA, respectively. Mortality from intracranial hemorrhage in the direct anticoagulant group was similar to that in the general population [standardized mortality ratio: 1.06, 95% confidence intervals (CI) 0.76-1.48], whereas it almost doubled in VKA group (1.92, 95% CI 1.49-2.46). When directly compared with the VKA cohort, the risk of death from intracranial hemorrhage halved with DOACs (hazard ratio 0.56, 95% CI 0.37-0.84).. The mortality rate of anticoagulated atrial fibrillation patients is increased with respect to the general population, particularly among patients treated with VKAs. The mortality rate for intracranial bleeding with DOACs is similar to that observed in the general population.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Italy; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K

Vitamin K antagonists (VKAs) are suspected of causing aortic valve calcification (AVC). The objective of this study was to clarify whether patients undergoing VKA treatment have increased AVC scores compared to patients treated with new oral anticoagulants (NOACs) and patients who never have been treated with VKA/NOAC.. We included participants from the population-based DANCAVAS trial (n = 15 048). Information on confounders was collected, and the AVC scores were measured on non-contrast computed tomography scans. The participants' medication data, including VKA and NOAC data, were collected from the Danish National Health Service Prescription Database. The final population consisted of 14 604 participants (67.4 years, 95% men) of whom 873 had been treated with VKA and 602 with NOAC. The association between AVC score and duration of anticoagulant use was investigated in an adjusted zero-inflated negative binomial regression model. For every year treated with VKA, the AVC score increased, on average, by 6% [ratio of expected counts (RECs) = 1.06; 95% confidence interval (CI) 1.02-1.10] compared to non-use. The results were consistent in sensitivity analyses excluding patients with known cardiovascular disease and statin users (REC = 1.07; 95% CI 1.02-1.11 and REC = 1.10; 95% CI 1.03-1.17, respectively). NOAC treatment was not significantly associated with AVC score in any of the corresponding models (REC = 1.03, 1.02, and 0.96).. Compared to no treatment with anticoagulants, VKA use was associated with increased AVC score, while a similar association could not be established for NOAC.

Topics: Administration, Oral; Anticoagulants; Aortic Valve; Atrial Fibrillation; Female; Humans; Male; State Medicine; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; Vitamin K

The objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real-world data.. A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism).. Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37-0.82 and 0.54, 0.26-1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29-0.58 and 0.41, 0.22-0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding.. There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Hemorrhage; Humans; Prospective Studies; Rivaroxaban; Stroke; Vitamin K

Efficacy and safety of vitamin K antagonists (VKAs) is optimised in atrial fibrillation (AF) patients when the International Normalised Ratio (INR) is 2.0-3.0. Anticoagulation control comparing different ethnic groups is limited, although epidemiological studies suggest poorer INR control in non-white cohorts.. VKA control was assessed retrospectively by time-in-the-therapeutic range (TTR) (Rosendaal method) and percentage INR-in-range (PINRR) in 991 White, Afro-Caribbean and South-Asian AF patients [overall mean (SD) age 71.6 (9.4) years; 55% male; mean (SD) CHA. Compared to Whites, mean (SD) TTR and PINRR were significantly lower in South-Asians [TTR 67.9% vs. 60.5%; PINRR 58.8% vs. 51.6%, respectively] and Afro-Caribbeans [TTR 67.9% vs. 61.3%; PINRR 58.8% vs. 53.1%, respectively], despite similar INR monitoring intensity. Logistic regression revealed non-white ethnicity [OR 2.62; 95% Confidence Interval [CI] (1.67-4.10) and OR 3.47 (1.44-8.34)] and anaemia [OR 1.65 (1.00-2.70) and OR 6.27 (1.89-20.94)] as independent predictors of both TTR and PINRR < 70%, respectively. At follow-up, 329 (33.2%) patients experienced ≥1 major adverse clinical event. Cardiovascular hospitalisation was significantly higher among South-Asians (32.3%) compared to the Whites and Afro-Caribbeans (21.3% vs 25.6% respectively).. Ethnic disparities in quality of anticoagulation control are evident, with South-Asians and Afro-Caribbeans having poorer control compared to Whites, despite similar intensity INR monitoring. Non-white ethnicity remained the strongest independent predictor of poor TTR and PINRR. Interventions to improve anticoagulation control need to be implemented, particularly targeting ethnic minority patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Ethnicity; Female; Humans; International Normalized Ratio; Male; Minority Groups; Retrospective Studies; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Perception; Prospective Studies; Stroke; Vitamin K

This study aimed to identify the time in therapeutic range (TTR) for dialysis patients on warfarin, and improve TTR with dietary review and intervention of interacting foods. We identified 151 patients undergoing hemodialysis in two units who were being treated with warfarin from January 1, 2010, through February 1, 2018, who were included in the overall TTR study. Of these, 15 patients were available to undergo the dietary intervention. International normalized ratio values were collected retrospectively for all eligible hemodialysis patients, and TTR was calculated for each period in which the patient was on hemodialysis. Patients who were available and agreed to the intervention underwent targeted dietician review of interacting foods, and their TTR post-treatment was calculated. The median (interquartile range [IQR]) TTR was 44 (IQR, 29 to 53) % among the 151 patients. Among the 15 patients who underwent the intervention, median (IQR) TTR was 52 (IQR, 32 to 56) pre-intervention and 51 (IQR, 38 to 69) post-intervention (P=0.53). TTR for dialysis patients is low in this overall cohort despite patients being seen at an integrated health care system. Focused improvement projects such as dietary review of interacting foods may help increase a patient's TTR.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Diet; Diet Therapy; Female; Humans; International Normalized Ratio; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Time Factors; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Body Mass Index; Humans; Obesity; Vitamin K

 The ABC (age, biomarkers, and clinical history)-stroke and ABC-bleeding are biomarker-based scores proposed to predict stroke and bleeding, but non-specificity of biomarkers is common, predicting different clinical events at the same time. We assessed the predictive performance of the ABC-stroke and ABC-bleeding scores, for outcomes beyond ischemic stroke and major bleeding, in a cohort of atrial fibrillation (AF) patients..  We included AF patients stable on vitamin K antagonists for 6 months. The ABC-stroke and ABC-bleeding were calculated and the predictive values for myocardial infarction (MI), acute heart failure (HF), a composite of cardiovascular events, and all-cause deaths were compared..  We included 1,044 patients (49.2% male; median age 76 [71-81] years). During 6.5 (4.3-7.9) years, there were 58 (5.6%) MIs, 98 (9.4%) acute HFs, 167 (16%) cardiovascular events, and 418 (40%) all-cause deaths. There were no differences in mean ABC-stroke and ABC-bleeding scores in patients with/without MI (.  In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict "sick" patients or poor prognosis overall.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Atrial Fibrillation; Biomarkers; Cardiovascular Agents; Cause of Death; Comorbidity; Death, Sudden, Cardiac; Decision Support Techniques; Female; Heart Failure; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Prognosis; ROC Curve; Severity of Illness Index; Stroke; Vitamin K

Intracranial hemorrhage (ICH) is associated with severe prognosis and recurrent risk. This impacts on the decision to resume anticoagulation in atrial fibrillation (AF) or venous thromboembolism (VTE) patients. Purpose of our study is to evaluate the incidence rate of recurrent ICH in patients with AF or VTE resuming anticoagulation after a first ICH episode.. We report data of two cohorts of AF or VTE after a first ICH. The Vitamin K antagonist (VKA) cohort (166 patients) derives from CHIRONE Study, the direct oral anticoagulant (DOAC) cohort (178 patients) derives from START2-Register RESULTS: The clinical characteristics of the two cohort are similar with the exception of more prevalence of history of previous stroke/TIA in DOAC patients with respect to VKA (p = 0.02) and serum creatinine levels>1.5 mg/dL in VKA patients with respect to DOAC(p = 0.0001). The index ICH was spontaneous in 66.4% and in 33.7% among DOAC and VKAs cohort respectively (p = 0.0001). During follow-up, 14 recurrent ICH were recorded; 9 (rate 2.5 × 100 patient-years) in VKA and 5 (rate 1.3 × 100 patient-years) in DOAC (Relative Risk 1.9; 95% CI 0.6-7.4; p = 0.2). The univariate logistic regression analysis showed that patients with recurrent ICH were more frequently males, hypertensive, with a history of previous Stroke/TIA and older than patients without recurrence. VKA patients showed a higher risk of recurrence with respect to DOAC patients (OR 1.9;95% CI 0.7-6.7).. A trend toward fewer ICH recurrences was detected among DOACs patients in comparison to the previously reported rate of patients on warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Male; Venous Thromboembolism; Vitamin K

Cancer may complicate the clinical course of nonvalvular atrial fibrillation (AF) but its association with cardiovascular events (CVEs) remains unclear. We performed a prospective cohort study including 2092 consecutive AF patients on vitamin K antagonists. Principal endpoint was the occurrence of CVEs including fatal/nonfatal myocardial infarction and ischemic stroke/transient ischemic attack and cardiovascular death. Secondary endpoints were major adverse cardiac events (MACEs) and thromboembolism (TE). Mean age was 73.7 ± 9.1 years and 42.1% were women; 367 (17.5%) patients had cancer: 21% gastrointestinal (GI), 10% respiratory, 28% genitourinary and 41% had other localization. Cancer patients were older but with similar comorbidities than those without. During a mean of 35.9 months, 203 CVEs occurred (incidence rate [IR] = 3.24 per 100 patient-years): 133 MACEs (IR = 2.12 per 100 patient-years) and 70 TE (IR = 1.12 per 100 patient-years). Multivariable Cox proportional hazards regression analysis showed an association between GI cancer and MACE occurrence (hazard ratio [HR] = 3.22, 95% confidence interval [CI] = 1.59-6.52, P = .001) and between respiratory cancer and TE (HR = 3.37, 95% CI = 1.30-8.75, P = .013). These associations were confirmed at competing risk analysis. In conclusion, AF patients with cancer have specific vascular outcomes according to cancer site, as indicated by the higher risk of MACE and TE in patients with gastrointestinal and respiratory cancer, respectively.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Comorbidity; Cross-Sectional Studies; Female; Humans; Male; Myocardial Ischemia; Neoplasms; Proportional Hazards Models; Prospective Studies; Thromboembolism; Vitamin K

Using nationwide Danish registries, we conducted a population-based case-crossover study evaluating the association between switching from a vitamin K antagonist (VKA) to a direct oral anticoagulant (DOAC), and vice versa, and 30-day risks of bleeding and arterial thromboembolism in patients with atrial fibrillation (AF). The case-crossover population was identified among oral anticoagulant users during 2011-2018 (n = 123,217) as patients with AF with 1) a case-defining outcome and 2) an anticoagulant switch during the 180 days preceding the outcome. Odds ratios were estimated using conditional logistic regression by comparing the occurrence of switching during the 30-day window immediately preceding the outcome to that in reference windows in the same individual 60-180 days before the outcome. The case-crossover populations for switching from VKA to DOAC and DOAC to VKA comprised 1,382 and 287 case patients, respectively. Switching from VKA to DOAC, but not from DOAC to VKA, was associated with an increased short-term risk of bleeding (odds ratio = 1.42; 95% confidence intervals: 1.13, 1.79, and 1.06; and 0.64, 1.75, respectively) and ischemic stroke (odds ratio = 1.74; 95% confidence intervals: 1.21, 2.51, and 0.92; and 0.46, 1.83, respectively). Our findings suggest that switching from VKA to DOAC is an intermittent risk factor of bleeding and ischemic stroke in patients with AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Cross-Over Studies; Drug Substitution; Female; Hemorrhage; Humans; Male; Thromboembolism; Vitamin K

Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) require chronic anticoagulation due to high thromboembolic risk. Evidence supporting the use of non-vitamin K oral anticoagulants (NOACs) in patients with HCM remains sparse, and there are no data regarding the use of NOACs in patients with HCM undergoing catheter ablation of AF.. Observational nonrandomized study in four European centers. We aimed to investigate the safety and efficacy of NOACs compared with vitamin K antagonists (VKAs) in patients with HCM undergoing catheter ablation for AF.. A total of 137 patients with HCM (mean age: 55.0 ± 13.4, 29.1% female) underwent 230 catheter ablations for AF (1.7 ± 1.0 per patient). A total of 55 patients (39.4%) underwent 70 procedures (30.4%) on NOAC, while the remaining were on VKA. Warfarin (97.6%) and rivaroxaban (56.4%) were the most frequently used agents in the respective groups. No procedure-related deaths were reported. We observed no significant difference in the rate of thromboembolism (VKA: 0.6%; NOAC: 0%; p = 1.0) or minor bleeding (VKA: 0.6%; NOAC: 1.4%; p = .54). There was a nonsignificant trend towards a lower incidence of major bleeding (VKA: 6.9%; NOAC: 1.4%; p = .09).. These preliminary data suggest that NOACs are at least as safe and effective as VKAs in patients with HCM undergoing catheter ablation for AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Catheter Ablation; Female; Humans; Male; Middle Aged; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Obesity; Primary Prevention; Vitamin K

Anticoagulation with oral antagonists without vitamin K (NOACs) is the preferred therapy for stroke prevention in atrial fibrillation. Vitamin K antagonists (VKA) should only be prescribed if there are contraindications to NOAC (e. g. mechanical heart valves, rheumatic mitral stenosis). The guideline recommendations are based on dedicated NOAC development programs with large randomized clinical phase III studies. Data from observational studies on the efficacy and safety of NOACs compared to VKA are in general complementary to data stemming from the phase III studies. Due to their pharmacokinetic and dynamic properties, NOACs are much easier to handle than VKA. Amongst other advantages, this implies that in case of short interruptions in anticoagulation therapy (e. g. for surgical procedures), bridging therapy with heparin is no longer required. This will reduce bleeding complications dramatically.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Vitamin K

Topics: Acute Coronary Syndrome; Acute Disease; Aspirin; Atrial Fibrillation; Clopidogrel; Combined Modality Therapy; Cyclophosphamide; Dabigatran; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stents; Stroke; Vitamin K

 Existing evidence on the association between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) and cancer is limited and contradictory. No observational studies have been conducted to simultaneously address the cancer safety of VKAs and DOACs. The objective of this study was to determine whether use of VKAs and DOACs, separately, when compared with nonuse, is associated with cancer overall and prespecified site-specific incidence..  Using the United Kingdom Clinical Practice Research Datalink, we identified patients newly diagnosed with nonvalvular atrial fibrillation (NVAF) between 2011 and 2017. Using a time-varying exposure definition, each person-day of follow-up was classified as use of (1) VKAs, (2) DOACs, (3) VKAs and DOACs (drug switchers), and (4) nonuse of anticoagulants (reference). We also conducted a head-to-head comparison of new users of DOACs versus VKAs using propensity score fine stratification weighting. Hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer overall and prespecified subtypes were estimated using Cox proportional hazards models..  Compared with nonuse, use of VKAs was not associated with cancer overall (HR: 1.05, 95% CI: 0.91-1.22) or cancer subtypes. Similarly, use of DOACs was not associated with cancer overall (HR: 1.13, 95% CI: 0.93-1.37), but an association was observed for colorectal cancer (HR: 1.73, 95% CI: 1.01-2.99), and pancreatic cancer generated an elevated, though nonsignificant HR (HR: 2.15, 95% CI: 0.72-6.44). Results were consistent in the head-to-head comparison..  Use of oral anticoagulants is not associated with the incidence of cancer overall among patients with NVAF. Possible associations between DOACs and colorectal and pancreatic cancer warrant further study.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Neoplasms; Vitamin K

Nurses play a central role in the management of atrial fibrillation (AF) patients. An unresolved question is whether a nurse-led clinic would improve clinical outcomes. Herein, we investigated the impact of a nurse-led clinic on anticoagulation therapy and clinical outcomes in a cohort of naïve AF patients.. Prospective study including AF patients starting vitamin K antagonists (VKAs) into a nurse-led AF clinic. These patients were followed in this specific AF clinic. Additionally, AF patients already taking VKAs for 6 months followed according to the routine clinical practice were included as comparison group. The quality of anticoagulation was assessed at 6 months. Efficacy and safety endpoints were recorded during follow-up.. We included 223 patients (Nurse-led clinic: 107; Usual care: 116). The mean time in therapeutic range and the proportion of INRs within the therapeutic range were similar in both groups. During 2.06 (IQR 1.01-2.94) years of follow-up, 64 (28.7%) patients changed to direct-acting oral anticoagulants. The proportion of switchers was higher in the nurse-led clinic (37.4%) than in the usual care group (20.7%) (P = .006) and these patients spent less time to switch (2.0 [IQR 0.7-2.9] vs 6.0 [IQR 3.7-11.2] years; P < .001). Importantly, the annual rate of ischaemic stroke/TIA was significantly lower in the nurse-led clinic (0.47%/year vs 3.88%/year, P = .016), without differences in safety endpoints.. A nurse-led AF clinic may offer a "patient-centered" review and holistic follow-up, and it would be associated with a reduction of ischaemic stroke/TIA, without increasing bleeding complications. Further studies should confirm these results.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Prospective Studies; Stroke; Vitamin K

The time in therapeutic range (TTR) of patients with venous thromboembolism (VTE) treated with vitamin K antagonists (VKA) is usually below recommended, leading to higher frequency of vascular events, bleeding and mortality. The SAMe-TT2R2 prediction score discriminates those patients with high or low probability of obtaining poor INR control and its use is recommended in patients with atrial fibrillation. Its usefulness has been evaluated in patients with VTE, with conflicting results.. We included consecutive patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry, treated with VKA for >90 days and a minimum of 3 INR determinations. We analyzed the relationship between the SAMe-TT. 3893 patients were included and classified in high (1411 patients) or low (2482 patients) probability of obtaining poor INR control according to the total score obtained (0-1 points versus 2 points, respectively). TTR, calculated by direct method and Rosendaal method, was 51.2 (±23.4) and 55.4 (±25.9) in the high probability group; and 54.4 (±23.0) and 58.2 (±25.6) in the low probability group, respectively (p < 0.001 for both comparisons). The outcomes were similar between groups. The predictive capacity of the SAMe-TT2R2 score showed an area under the ROC curve of 0.54 (CI 95% 0.52-0.56) and 0.53 (CI 95% 0.51-0.55).. In patients with VTE treated with VKA, the SAMe-TT2R2 score discriminated those patients with high probability of obtaining poor INR control, but with a low predictive capacity. Further studies are required to assess the usefulness of the score in clinical decision-making.

Topics: Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Prospective Studies; Registries; Venous Thromboembolism; Vitamin K

Direct oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population.. Retrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts.. Patients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29-1.35) and a lower risk for bleeding (0.89; 0.88-0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82-2.03), apixaban (1.52; 1.46-1.58), and rivaroxaban (1.13; 1.10-1.17) but not for edoxaban (0.88; 0.74-1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83-0.88), apixaban (0.71; 0.70-0.73), and edoxaban (0.29; 0.17-0.51) but not for rivaroxaban (1.03; 1.01-1.04).. This study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Vitamin K; Young Adult

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Vitamin K

The uptake rate of non-vitamin K oral anticoagulants (NOAC) for the treatment of non-valvular atrial fibrillation (AF) was far lower in the Netherlands (NL) compared to Belgium (BE). Also, patients on VKA in NL were treated with a higher target international normalized ratio (INR) range of 2.5 to 3.5.. To explore the effect of these differences on thromboembolism (TE) and bleeding.. Data from the GARFIELD-AF registry was used. Patients with new-onset AF and ≥1 investigator-determined risk factor for stroke were included between 2010 and 2016. Event rates from 2 years of follow-up were used.. In GARFIELD-AF, despite similar characteristics, patients on anticoagulants were treated differently in NL and BE. Although the rate of major bleeding was 33% higher in NL, variations in bleeding, mortality, and TE rates were not statistically significant.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Belgium; Female; Humans; Netherlands; Registries; Risk Factors; Stroke; Vitamin K

The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited.. We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years.. Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated.. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively).. NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Topics: Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Republic of Korea; Stroke; Thiazoles; Vitamin K; Warfarin

Treatment burden (TB) refers to self-perceived cumulative work patients do to manage their health. Using validated tools, TB has been documented in several chronic conditions, but not atrial fibrillation (AF). We measured TB and analysed its determinants and impact on quality of life (QoL) in an AF cohort.. A single-centre study prospectively included consecutive adult AF patients and non-AF controls managed from 1 April to 21 June 2019, who voluntarily and anonymously answered the TB questionnaire (TBQ) and 5-item EQ-5D QoL questionnaire; TB was calculated as a sum of TBQ points (maximum 170) and expressed as proportion of the maximum value. Of 514 participants, 331 (64.4%) had AF. The mean self-reported TB was 27.6% among AF patients and 24.3% among controls, P = 0.011. The mean TB was significantly higher in patients taking vitamin K antagonists (VKAs) vs. those taking non-VKA antagonist oral anticoagulants (NOAC; 29.5% vs. 24.7%, P = 0.006). The highest item-specific TB was reported for healthcare system organization-related items (e.g. visit appointment), diet, and physical activity modifications. On multivariable analyses, female sex, younger age, and permanent AF were associated with a higher TB, whereas NOACs and electrical AF cardioversion exhibited an inverse association; TB was an independent predictor of decreased QoL (all P < 0.05).. Our study provided clinically relevant insights into self-perceived TB among AF patients. Approximately one in four patients with AF have a high TB. Specific AF treatments and optimization of healthcare system-required patient activities may reduce the self-perceived TB in AF patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Humans; Quality of Life; Self Report; Stroke; Vitamin K

The aim of this study was to compare long-term all-cause mortality between direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after transcatheter aortic valve replacement (TAVR).. The optimal anticoagulant agent for patients with AF after TAVR has not been clarified.. OCEAN (Optimized Transcatheter Valvular Intervention) is a prospective, multicenter, observational cohort registry comprising 2,588 patients who underwent TAVR between October 2013 and May 2017. Of these, 403 patients (15.6%) with AF on anticoagulant therapy were identified, of whom 227 (56.3%) were prescribed DOACs and 176 (43.7%) were prescribed VKAs. Patients who successfully discharged after TAVR were stratified into DOAC and VKA groups on the basis of the prescription of anticoagulant agents, and the analyses started from discharge.. In total, 33.3% of patients were men. The mean age was 84.4 ± 4.7 years, and the average CHA. Compared with VKAs, DOACs might be associated with lower long-term all-cause mortality in patients with concomitant AF who are successfully discharged after TAVR. This finding warrants investigation in ongoing prospective randomized trials.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Prospective Studies; Risk Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Warfarin, a vitamin K antagonist (VKA), is known to promote arterial calcification (AC). In the present study, we conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis (MESA); 6655 participants were included. From MESA data, we found that AC was related to both age and vitamin K; furthermore, the score of AC increased with SASP marker including interlukin-6 (IL-6) and tumor necrosis factor alpha (TNF-

Topics: Abdomen; Aged; Animals; Aortic Valve; Atrial Fibrillation; Biomarkers; Cellular Senescence; Dose-Response Relationship, Drug; Electrocardiography; Factor Analysis, Statistical; Female; Humans; Interleukin-6; Logistic Models; Male; Middle Aged; Multivariate Analysis; Phosphates; Rats, Sprague-Dawley; Risk Factors; Time Factors; Up-Regulation; Vascular Calcification; Vitamin K; Warfarin

To test the hypothesis that particulate matter with an aerodynamic diameter of less than 10 μm (PM. We included patients with AF whose condition was stable while taking VKAs (international normalized ratio, 2.0 to 3.0) for 6 months seen in a tertiary hospital (recruitment from May 1, 2007, to December 1, 2007). During a median follow-up of 6.5 years (interquartile range, 4.3 to 7.9 years), ischemic strokes, major bleeding, adverse cardiovascular events, and mortality were recorded. From 2007 to 2016, data on average temperature and PM. The study group included 1361 patients (663 [48.7%] male; median age, 76 years [interquartile range, 71 to 81 years]). High PM. In patients with AF taking VKAs, high PM

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Cold Temperature; Environmental Exposure; Female; Follow-Up Studies; Humans; Male; Middle Aged; Particulate Matter; Risk Factors; Seasons; Vitamin K

Real-world data about treatment convenience and satisfaction in Asian non-valvular atrial fibrillation (NVAF) patients after switching from vitamin K antagonists (VKAs) to non-VKA oral anticoagulants were evaluated.. In this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.. Treatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p<0.001 each vs baseline; satisfaction: p=0.0174 (visit 2), p=0.0004 (visit 3) compared with baseline). Factors predictive of higher (>80th percentile) response on treatment convenience were female sex, younger age (<75 years), higher baseline stroke risk, higher creatinine clearance and absence of concomitant hypertension, stroke or gastrointestinal diseases.. Dabigatran was associated with a significant improvement in treatment convenience and satisfaction after switching from VKAs when used for stroke prevention in NVAF patients from Southeast Asia and South Korea.

Topics: Aged; Anticoagulants; Antithrombins; Asia; Atrial Fibrillation; Dabigatran; Drug Substitution; Female; Humans; Longitudinal Studies; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Stroke; Time Factors; Treatment Outcome; Vitamin K

To evaluate the use of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in adult congenital heart disease (ACHD) and assess outcome in a nationwide analysis.. Using data from one of Germany's largest Health Insurers, all ACHD patients treated with VKAs or NOACs were identified and changes in prescription patterns were assessed. Furthermore, the association between anticoagulation regimen and complications including mortality was studied. Between 2005 and 2018, the use of oral anticoagulants in ACHD increased from 6.3% to 12.4%. Since NOACs became available their utilization increased constantly, accounting for 45% of prescribed anticoagulants in ACHD in 2018. Adult congenital heart disease patients on NOACs had higher thromboembolic (3.8% vs. 2.8%), MACE (7.8% vs. 6.0%), bleeding rates (11.7% vs. 9.0%), and all-cause mortality (4.0% vs. 2.8%; all P < 0.05) after 1 year of therapy compared with VKAs. After comprehensive adjustment for patient characteristics, NOACs were still associated with increased risk of MACE (hazard rate-HR 1.22; 95% CI 1.09-1.36) and increased all-cause mortality (HR 1.43; 95% CI 1.24-1.65; both P < 0.001), but also bleeding (HR 1.16; 95% CI 1.04-1.29; P = 0.007) during long-term follow-up.. Despite the lack of prospective studies in ACHD, NOACs are increasingly replacing VKAs and now account for almost half of all oral anticoagulant prescriptions. Particularly, NOACs were associated with excess long-term risk of MACE, and mortality in this nationwide analysis, emphasizing the need for prospective studies before solid recommendations for their use in ACHD can be provided.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Heart Defects, Congenital; Humans; Practice Patterns, Physicians'; Prospective Studies; Stroke; Vitamin K

Topics: Anticoagulants; Aortic Valve Stenosis; Atrial Fibrillation; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

There is a dearth of evidence regarding Health-Related Quality of Life (HRQoL) in nonvalvular atrial fibrillation (NVAF) patients undergoing oral anticoagulation therapy. Our objective was to describe HRQoL in NVAF patients on oral anticoagulation, focusing on uncontrolled patients on vitamin K antagonists (VKAs) versus controlled patients on VKAs or non-vitamin K antagonist oral anticoagulants (NOACs), in a real-world setting. Additionally, we assessed the clinical characteristics of patients with uncontrolled anticoagulation.. An observational, multicentre, and cross-sectional study, enrolling 38 Spanish Hospitals' Internal Medicine Departments. HRQoL was assessed using the validated Spanish version of the Sawicki questionnaire. High self-perceived HRQoL was indicated by high scores in the general treatment satisfaction and self-efficacy dimensions, and by low scores in the strained social network, daily hassles and distress dimensions.. Five hundred and one patients were included for assessment. Mean scores ± SD were closer to a high perceived HRQoL in controlled than uncontrolled patients for the five dimensions of the questionnaire: 4.9 ± 1.0 versus 3.6 ± 1.3 for general treatment satisfaction; 4.3 ± 1.0 versus 3.6 ± 1.0 for self-efficacy, 3.1 ± 0.9 versus 3.9 ± 1.1 for strained social network, 2.1 ± 0.8 versus 3.0 ± 1.0 for daily hassles and 1.8 ± 0.9 versus 2.6 ± 1.2 for distress.. HRQoL in patients with controlled anticoagulant status treated with NOACs or VKAs was better than in patients with uncontrolled anticoagulant status. This seems to indicate that anticoagulation control status influences perception of HRQoL, highlighting the importance of its evaluation when assessing HRQoL in NVAF patients.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Vitamin K

A 91-year-old Caucasian man on warfarin for atrial fibrillation presented in view of sudden-onset haemoptysis with fresh bleeding with clots immediately after having eaten a piping-hot traditional cheesecake (pastizz) and burning the soft-palate of his mouth. The haemoptysis had resolved by the time that the patient had arrived to hospital. On examination, a 2 cm by 2 cm dark red, solitary mass could be seen just anterior to the uvula. This was not causing any pain or discomfort to the patient. Blood results were mostly unremarkable except for a raised international normalised ratio (INR) of 3.53. The patient was administered 5 mg vitamin K orally in attempt to lower the INR level and warfarin was subsequently omitted for 7 days. He was also prescribed oral steroids on discharge. The lesion resolved in 7 days and warfarin was restarted then with no further consequences.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Burns; Food; Hematoma; Hemoptysis; Hot Temperature; Humans; International Normalized Ratio; Male; Palate, Soft; Uvula; Vitamin K; Warfarin

Non-vitamin K oral anticoagulants (NOACs) were shown to have better outcomes than warfarin for non-valvular atrial fibrillation (NVAF). Given limited local real-world data, this study aims to evaluate the safety and efficacy of NOACs versus warfarin for NVAF in Singapore.. This single-centre retrospective cohort study included 439 patients ≥ 21 years old that were newly prescribed with oral anticoagulants (OACs) for NVAF in 2015. Follow-ups for patients upon OAC initiation lasted either for 2 years or until the occurrence of bleeding or thromboembolism event or death (whichever was earlier). Primary endpoints included major bleeding and stroke, while secondary endpoints included overall bleeding and thromboembolic events. Time-to-events was evaluated via Kaplan-Meier survival analysis. Data on time in therapeutic range (TTR) and compliance were analysed.. NOACs were associated with similar stroke and major bleeding rates as warfarin for NVAF.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Singapore; Stroke; Vitamin K; Warfarin; Young Adult

To estimate the rate of non-vitamin K oral anticoagulant (NOAC) dosing that is lower- and higher-than-recommended and to describe the reasons for NOAC dose discordance with Health Canada prescribing information.. The OPTIMAL AF Programme was an observational cohort quality assessment initiative in which primary and specialty care physicians in eight provinces provided a snapshot of their anticoagulated non-valvular atrial fibrillation (NVAF) patients through either an electronic medical record (EMR) system or standardised, paper-based data collection methods.. Data on 1681 NVAF patients receiving oral anticoagulation (OAC) for stroke prevention was provided by 102 physicians. A NOAC was prescribed in 1379 patients (8%). The standard recommended dose was prescribed in 849 (76%) and reduced dose in 264 (24%). Concordance of the reduced dose with Health Canada prescribing information occurred in 154 patients (58%). The standard dose was concordant in 805 (95%). The main reasons for the use of discordant reduced doses were age of 80 years or more, elevated creatinine, prior bleeding or dose recommended by specialist.. The vast majority of Canadian patients meeting the Canadian Cardiovascular Society (CCS) guideline recommendations for OAC to decrease AF-related stroke risk were receiving product monograph-concordant NOAC dosing (85%). Nonetheless, this highlights the fact that an important proportion of patients were prescribed doses that are discordant and opportunities remain to improve NOAC dosing to optimise stroke prevention.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Canada; Cohort Studies; Female; Guideline Adherence; Humans; Male; Off-Label Use; Practice Patterns, Physicians'; Stroke; Vitamin K

Direct Oral Anticoagulants (DOACs) have shown to be at least effective and safer than anti-vitamin K (VKA) for the prophylaxis of cardioembolism during AF. These drugs do not need laboratory monitoring such as the VKA anticoagulants, but they are at risk of poor adherence and persistence as all drugs taken by mouth. Against this drawback, empathy may have an important role because it is important as a tool to be used for effective interpersonal communication. Patients like to be heard and understand that those who listen to them are immersed in their world. Empathy is part, and is a founding principle, of Narrative Medicine which today is a real discipline with many advantages because it is intrinsically therapeutic for the patient (in telling and being heard). Empathy prevents the disconnection that can intervene between the doctor and the patients. Have we ever wondered if we are sufficiently empathetic? Is it possible to measure our empathy? Yes, across Jefferson's scale. A high score on Jefferson's scale could certainly further improve the quality of the management of anticoagulated patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Empathy; Humans; Vitamin K

Emerging evidence indicates combination therapy with anticoagulants and antiplatelet agents for atrial fibrillation (AF) will be increasingly required. Numerous studies compare the efficacy and cost-effectiveness of anticoagulation alone in AF, i. e., non-vitamin K oral anticoagulants (NOACs) vs. warfarin. However, the addition of antiplatelet agents with their potential for decreasing thromboembolic stroke counter-balanced by an increased bleeding risk has received less attention. Thus, we evaluated the cost-utility of this combination therapy.. We obtained event estimates from our recent meta-analysis of four randomized clinical trials designed to compare NOACs with warfarin in patients with AF. We examined patient subgroups within each trial that received antiplatelet therapy in addition to anticoagulation. Utilities were derived from the literature and cost estimates from the German health-care system. A decision tree was constructed and populated with these parameters. We used a 1-year time horizon because combination therapy is not recommended beyond this time. We calculated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). The derived ICER was 13,168.50 € per QALY. NOAC prices exerted considerable influence on the calculation. Nevertheless, there is potential for ICER shifts in favor of warfarin, e.g., if warfarin-mediated anticoagulation control is improved and thereby adverse events decrease. Conversely, if NOAC adherence decreases, adverse events could increase.. The derived ICER was 13,168.50 € per QALY, consistent with NOACs being cost-effective vs. warfarin when anticoagulation is used with antiplatelet agents. Nevertheless, country-, practice-, and patient-related factors influence the ICER. Our cost-utility calculation should be used a starting point for decision-making.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Platelet Aggregation Inhibitors; Stroke; Vitamin K; Warfarin

The aim of the study was to compare clinical characteristics of real-life atrial fibrillation (AF) patients with populations included in randomized clinical trials (ROCKET AF and RE-LY).. The analysis included 3528 patients who are participants of the ongoing, multicentre, retrospective CRAFT study. The study is registered in ClinicalTrials.gov: NCT02987062. The study is based on a retrospective analysis of hospital records of AF patients treated with vitamin K antagonists (VKAs) (acenocoumarol, warfarin) and non-vitamin K oral anticoagulants (NOACs) (dabigatran, rivaroxaban). CHADS2 score was used for risk of stroke stratification.. VKA was prescribed in 1973 (56.0%), while NOAC in 1549 (44.0%), including dabigatran - 504 (14.3%) and rivaroxaban - 1051 (29.8%), of the 3528 patients. VKA patients in the CRAFT study were at significantly lower risk of stroke (CHADS2 1.9 ± 1.3), compared with the VKA population from the RE-LY (2.1 ± 1.1) and the ROCKET-AF (3.5 ± 1.0). Patients in the CRAFT study treated with NOAC (CHADS2 for patients on dabigatran 150 mg - 1.3 ± 1.2 and on rivaroxaban - 2.2 ± 1.4) had lower risk than patients from the RE-LY (2.2 ± 1.2) and the ROCKET AF (3.5 ± 0.9).. Real-world patients had a lower risk of stroke than patients included in the RE-LY and ROCKET AF trials.

Topics: Administration, Oral; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Humans; Male; Randomized Controlled Trials as Topic; Retrospective Studies; Stroke; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as preferred options for stroke prevention in patients with atrial fibrillation (AF) versus warfarin by guidelines worldwide.. This study aimed to evaluate the cost-effectiveness of each NOAC in a Thai health care environment, a country with upper middle-income economies based on the World Bank's classification.. A lifetime Markov model was created from a Thai societal perspective. The model consisted of 19 health states separated into two cycles: event cycle and consequence cycle. The consequences of AF included in the model were ischaemic stroke, intracranial haemorrhage, extracranial haemorrhage, and myocardial infarction. All NOACs available in Thailand (dabigatran 150 mg and 110 mg twice daily; rivaroxaban 20 mg once daily; apixaban 5 mg twice daily; edoxaban 60 mg and 30 mg once daily) were assessed using warfarin with an international normalised ratio of 2-3 as the reference. Inputs were a combination of published literature and local data when available. A willingness-to-pay of 160,000 Thai baht (THB)/quality-adjusted life year (QALY) was used as the threshold of being cost-effective. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were estimated.. All NOACs were not cost-effective strategies for the Thai AF population. The ranking of incremental cost-effectiveness ratios from lowest to highest were apixaban 5 mg twice daily (THB 692,136 or US$21,862) followed by edoxaban 60 mg once daily (THB 911,772 or US$28,799), edoxaban 30 mg once daily (THB 913,749 or US$28,861), dabigatran 150 mg twice daily (THB 1,102,106 or US$34,811), dabigatran 110 mg twice daily (THB 1,195,347 or US$37,756), and rivaroxaban 20 mg once daily (THB 1,347,650 or US$42,566). Cost-effectiveness acceptability curve indicated that apixaban had the highest potential to be a cost-effective strategy versus other NOACs.. Our findings indicated that all NOACs were not cost-effective in the Thai AF population. Of the NOACs, apixaban may be the most likely to be cost-effective. These data may be useful for policymakers to perform a comprehensive evaluation of these agents for formulary decision and pricing negotiation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Humans; Male; Thailand; Vitamin K; Warfarin

To compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study.. The FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received.. A total of 2178 patients were included in the study (mean age 73.8±9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke-0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032-, severe bleedings-2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044-, cardiovascular death-1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009-, and all-cause death-3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016-. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death.. Compared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Female; Follow-Up Studies; Humans; Incidence; Male; Outpatients; Prognosis; Prospective Studies; Spain; Stroke; Survival Rate; Time Factors; Vitamin K

Clinical trials have indicated that the direct-acting oral anticoagulants dabigatran and rivaroxaban have better risk/benefit profiles than do vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (NVAF).. Our objective was to compare the 1-year real-life risk of major clinical events with dabigatran or rivaroxaban versus VKAs for NVAF.. This was a high-dimensional propensity score (hdPS)-matched cohort study of new users of dabigatran, rivaroxaban or VKAs for NVAF in the French national healthcare systems database in 2013 followed-up for 1 year [22]. Hazard ratios (HRs) with 95% confidence intervals (CIs) for clinical events and death were determined during exposure.. In 2013, a total of 103,101 new anticoagulant users had definite NVAF: 44,653 VKA, 27,060 dabigatran, and 31,388 rivaroxaban. In matched populations, HRs were as follows for dabigatran versus VKAs (20,489 per group): stroke and systemic embolism (SSE) 0.75 (95% CI 0.63-0.88), clinically relevant bleeding (CRB) 0.58 (95% CI 0.51-0.66), hemorrhagic stroke (HS) 0.22 (95% CI 0.14-0.36), gastrointestinal bleeding (GIB) 0.98 (95% CI 0.80-1.19), acute coronary syndrome (ACS) 0.79 (95% CI 0.65-0.95), death 0.74 (95% CI 0.67-0.82), composite (any of the above) 0.71 (95% CI 0.66-0.76). For matched rivaroxaban versus VKA (23,053 per group) HRs were as follows: SSE 0.98 (95% CI 0.85-1.14), CRB 0.83 (95% CI 0.75-0.92), HS 0.65 (95% CI 0.49-0.87), GIB 1.08 (95% CI 0.90-1.30), ACS 0.84 (95% CI 0.71-1.00), death 0.77 (95% CI 0.71-0.84), composite 0.84 (95% CI 0.79-0.89). Numbers needed to treat to observe one fewer death were 49 ± 0.05 with dabigatran or rivaroxaban versus VKAs.. Consistent with results from clinical trials and other observational studies, dabigatran and rivaroxaban were at least as effective and safer than VKAs for the prevention of thromboembolic events in NVAF over 1 year in the French population.. European Medicines Agency EUPAS 13017 (www.encepp.eu) Clinicaltrials.gov id NCT02785354.

Topics: Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Cohort Studies; Dabigatran; Data Systems; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Male; Propensity Score; Rivaroxaban; Vitamin K

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Embolism; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Rivaroxaban; Stroke; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

Topics: Anemia; Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Pyridines; Thiazoles; Vitamin K

Background Although the majority of clinical guidelines indicate the use of NOAC (nonvitamin K antagonist oral anticoagulant) over vitamin K antagonist in nonvalvular atrial fibrillation patients, there is no information on real-world prescription factors that lead to a specific type of oral anticoagulant selection. Objective To evaluate the prescription factors for choosing a specific oral anticoagulant for nonvalvular atrial fibrillation patients in Korea. Setting Nationwide sampled database in South Korea. Methods In this study, we defined nonvalvular atrial fibrillation patients as having one or more hospitalizations or two or more out-patient visits with a stroke risk score (CHA2DS2-VASc scores) ≥ 2 eligible for oral anticoagulant therapy from Jan 1st, 2016 to Dec 31st, 2016. Baseline characteristics were analyzed, including sex, age, comorbidities, CHA2DS2-VASc, bleeding risk score (mHAS-BLED), prescribing specialty, insurance type, medical institution type and location. Univariate and multivariate logistic regression analyses were conducted for being prescribed NOAC compared with vitamin K antagonist. Main outcome measure Adjusted odds ratio of the NOAC group and vitamin K antagonist group. Results Of 9,226 patients eligible for oral anticoagulant therapy, 4999 patients (54.2%) received oral anticoagulant therapy, and 4517 patients took NOAC or vitamin K antagonist only during the study period. Prior stroke, transient ischemic attack, thromboembolism, thyroid disease, dyslipidemia, cancer, mHAS-BLED ≥ 5, in-patient care, and specialty in internal medicine and neurology were positive predictors of NOAC use over vitamin K antagonist, whereas young age (≤64), renal dysfunction, and secondary care institution were negative predictors of NOAC use over vitamin K antagonist. Conclusions The presence of comorbidities was linked to NOAC use over vitamin K antagonist, which is different from prescription factor studies in other countries and requires further study.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Hemorrhage; Humans; Male; Middle Aged; Republic of Korea; Stroke; Vitamin K

  The quality of chronic anticoagulation and predictor factors of poor anticoagulant control in patients under acenocoumarol were unknown in North Africa.. It is an observational study, carried out between November 2015 and November 30, 2016. The international normalized ratio (INR) values were prospectively obtained, and TTR was calculated using the Rosendaal method.. Overall, 215 patients were included in this study, with a mean age of 63±0,8 years. The prevalence of poor anticoagulation control was 78.1%; 95% CI [72.2-83.2] (168 patients with TTR less than 65%). The median TTR with the Rosendaal method was 44.4%. After multivariate adjustment, variables significantly associated with adequate anticoagulation level were: history of ischemic stroke (Adjusted OR equal to 4.3, 95% CI: 1.4-12.9), associated prescription of antiplatelet therapy (Adjusted OR equal to 3.5, 95% CI: 1.1-11.2), daily prescribed dose of coumarins less than 6 mg (Adjusted OR equal to 6.4, 95% CI: 1.1- 36) and lower risk of bleeding assessed as HAS-BLED score (Adjusted OR: 0.5, 95% CI: 0.3-0.8).. The quality of anticoagulation management with VKA among outpatients who received acenocoumarol was suboptimal. Strategies should be undertaken by clinicians and patients to improve the quality of anticoagulation, to address challenges to adverse cardiovascular outcomes in individuals treated with chronic anticoagulation.

Topics: 4-Hydroxycoumarins; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Drug Monitoring; Female; Humans; Indenes; Male; Medication Adherence; Middle Aged; Outpatients; Prevalence; Socioeconomic Factors; Thromboembolism; Time Factors; Treatment Outcome; Tunisia; Vitamin K

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Agents; Combined Modality Therapy; Drug Therapy, Combination; Elective Surgical Procedures; Female; Fibrinolytic Agents; Hemorrhage; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Multicenter Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Purinergic P2Y Receptor Antagonists; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome; Vitamin K

Oral anticoagulant therapy (VKA) is nowadays the mainstay of treatment in primary and secondary stroke prevention in patients with atrial fibrillation. Given the limited risk-benefit ratio of vitamin K antagonists, pharmacological research has been directed towards the development of products that could overcome these limits, new oral anticoagulants were recently introduced: dabigatran, rivaroxaban, apixaban, and edoxaban.. Scope of the present study was to examine patterns of use, effectiveness, safety and mean annual cost per patient of anticoagulant treatment for non-valvular AF in real clinical practice.. A retrospective observational cohort study, by using administrative databases (drugs, hospitalizations, clinical visits, lab tests, population registry), was conducted in the Local Health Unit (LHU) of Treviso, Italy, from January 1, 2012 to December 31, 2016.. 5597 subjects were selected, 2171 of which satisfied all inclusion criteria. In particular 1355 patients were treated with VKA, 577 patients were treated with NOAC, and 239 patients were treated initially with VKA and subsequently switched to NOAC (switch group). NOAC treatment showed to be superior to VKA and this superiority was statistically significant on both end-points: patients in the NOAC group reported less cardiovascular events (9,9%) and less bleeding episodes (5,5%) versus VKA patients (14,6% and 11,4%; p<,0001 and p = 0,0049, respectively). The mean cost per patient per year was respectively € 1323,9 for patients treated with NOAC versus € 1003,3 for patients treated with VKA. Cost difference appears to be largely driven by drug cost (€ 767,9 for NOAC versus € 17,7 for VKA patients) and by specialist visits and laboratory tests (€ 318,4 for NOAC versus € 733,4 for VKA patients).. In this retrospective real-world study treatment with NOAC showed to be associated with significant reductions of CV events and bleeding events compared to VKA use, albeit at a higher NHS' direct cost per patient/year, mainly due to higher drug therapy cost.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Costs and Cost Analysis; Female; Follow-Up Studies; Humans; Male; Risk Factors; Thromboembolism; Treatment Outcome; Vitamin K

Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to  vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cohort Studies; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Sex Factors; Stroke; Vitamin K

Elderly patients in long-term treatment with vitamin K antagonists (VKAs) are at high risk of osteoporotic fractures compared with the background population. It has been speculated that the choice of oral anticoagulant (OAC) may affect the risk of osteoporotic fractures.. The risk of osteoporotic fractures was evaluated among patients with atrial fibrillation treated with VKA or direct oral anticoagulants (DOACs).. Patients were identified using the Danish national registries. Patients were included only if they had no prior use of osteoporosis medication and they had undergone 180 days of OAC treatment. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint.. Overall, 37,350 patients were included. The standardized absolute 2-year risk of any fracture was low among DOAC-treated patients (3.1%; 95% CI: 2.9% to 3.3%) and among VKA-treated patients (3.8%; 95% CI: 3.4% to 4.2%). DOAC was associated with a significantly lower relative risk of any fracture (hazard ratio [HR]: 0.85; 95% CI: 0.74 to 0.97), major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with DOAC had a significantly lower relative risk of experiencing any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93).. In a nationwide population, the absolute risk of osteoporotic fractures was low among patients with atrial fibrillation on OAC, but DOAC was associated with a significantly lower risk of osteoporotic fractures compared with VKA.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Denmark; Female; Fracture Healing; Humans; Male; Middle Aged; Osteoporotic Fractures; Proportional Hazards Models; Registries; Retrospective Studies; Risk Factors; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Osteoporotic Fractures; Stroke; Vitamin K; Warfarin

Atrial fibrillation is the most common heart rhythm disorder in the general population. It is associated with increased cardiovascular morbidity and mortality. Given this risk, anticoagulant therapy is vital.. To estimate the incidence of thromboembolic and hemorrhagic events in patients with Atrial fibrillation and treated by oral anticoagulant in a cardiology department.. We carried out an observational longitudinal study over a period of three years (January 2013 - December 2015) in the external consultation of cardiology of Farhat Hached hospital of Sousse. Pre-established individual records were used as a source and tool for data collection.. Overall, 200 patients were eligible. Forty-nine percent had valvular atrial fibrillation. After an average follow-up of 2.6 years, 15 thromboembolic events were noted affecting 13 patients (6.5%), with an incidence of 2.8%. We found a significant association between TTR <50% and the occurrence of stroke and transient ischemic events. Half of the patients had minor bleeding and 9.5% had major bleeding, with an incidence of 3.6%. No significant correlation between these accidents and the TTR was found. In addition, 9.5% of patients were hospitalized for international normalized ratio equilibration. They were mainly patients with valvular atrial fibrillation (72%) (p = 0.002).. Anticoagulant therapy with anti-vitamin-K remains the most adequate treatment. Thus, a well-conducted treatment ensures a reduction in thromboembolic risk and minimizes the occurrence of hemorrhages inherent to this therapy. Therefore, an assessment of the quality of anticoagulation is essential.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Incidence; Indenes; Longitudinal Studies; Male; Middle Aged; Risk Factors; Stroke; Thromboembolism; Tunisia; Vitamin K

The use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and bioprosthetic heart valve is still controversial. The aim of this study was to compare the tolerability and effectiveness of treatment with DOACs versus vitamin K antagonists (VKAs) in patients with AF and a bioprosthetic heart valve in clinical practice.. Data for this study were sourced from the multicenter, prospectively maintained AF Research Database (NCT03760874), which includes all patients with AF undergoing follow-up at participating centers through outpatient visits every 3-6 months. The rates of occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism), major bleed, and intracranial hemorrhage (ICH) were assessed. These data were used for quantifying the net clinical benefit (NCB) of DOACs versus VKAs, in accordance with the following formula: (Thromboembolic events incidence rate with VKAs - Thromboembolic events incidence rate with DOACs) - Weighting factor × (ICH rate with DOACs - ICH incidence rate with VKAs). The database was retrospectively queried for patients with AF who were prescribed a DOAC or VKA and had a history of bioprosthetic heart valve replacement.. A total of 434 patients with AF (DOACs, n = 211; VKAs, n = 223) were identified. Propensity score matching identified 130 patients prescribed DOACs (apixaban, 55.4%; rivaroxaban, 30.0%; dabigatran, 13.1%; edoxaban, 1.4%) and the same number of VKA recipients (warfarin, 89.2%; acenocoumarol, 10.8%). The mean (SD) duration of follow-up was 26.8 (2.3) months. The incidence rates of thromboembolic events were 1.3 per 100 person-years in the DOAC group versus 2.0 per 100 person-years in the VKA group (P = 0.14). The incidence rates of major bleed events were 2.6 per 100 person-years in the DOAC group versus 4.9 per 100 person-years in the VKA group (P = 0.47). The incidence rates of ICH were 0.38 per 100 person-years in the DOAC group versus 1.16 in the VKA group (hazard ratio = 0.33; 95% CI, 0.05-2.34; P = 0.3). A positive NCB of DOACs over VKAs of +1.87 was found.. According to these data from clinical practice, DOACs seem to be associated with a greater NCB versus VKAs in patients with AF with a bioprosthetic heart valve, primarily due to lower rates of both major bleeds and thromboembolic events.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Prosthesis; Humans; Retrospective Studies; Thromboembolism; Vitamin K

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations.

Topics: Anticoagulants; Atrial Fibrillation; Drug Monitoring; Health Services Needs and Demand; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; History, 20th Century; History, 21st Century; Humans; Multicenter Studies as Topic; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thrombophilia; Vitamin K

Most invasive procedures require the interruption of oral anticoagulation. In 2015, an international randomised trial demonstrated that perioperative bridging caused more harm than benefit in most anticoagulated patients with atrial fibrillation, leading to a more restrictive Dutch national guideline in April 2016. The objective of the present study was to analyse the integration of the 2016 Dutch guideline for perioperative antithrombotic management from after publication until update of hospital protocols.. This is a retrospective cohort study of patients on vitamin K antagonists undergoing a surgical procedure between April 2016 and June 2017.. The proportion of high-risk patients with venous thromboembolism or atrial fibrillation receiving bridging therapy decreased from 91% and 77%, respectively at the start of the study to 33% in both groups in the last months. In high-risk patients with a mechanical heart valve, the bridging rate remained stable at 70-80% for 12 months and increased to 100% in the last 3 months. Protocol adherence for high-risk patients decreased from 80% to below 43%. The 30-day incidence of major bleeding was 4.1% (15.2% in bridged patients and 0.7% in non-bridged patients) and 10.3% for clinically relevant non-major bleeding (23.9% in bridged patients and 6.0% in non-bridged patients). The incidence of thrombo-embolism was 0.5%.. New evidence from the Dutch national guideline on perioperative bridging was adopted by physicians before the local hospital protocol was updated. Low incidence of thromboembolism in non-bridged patients and high incidence of bleeding in bridged patients support a more restrictive bridging policy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Female; Guideline Adherence; Guidelines as Topic; Humans; Male; Middle Aged; Netherlands; Perioperative Care; Retrospective Studies; Thromboembolism; Venous Thromboembolism; Vitamin K

The arrival of direct-acting oral anticoagulants (DOACs) has led to a change in the management of non-valvular atrial fibrillation (NVAF) in recent years. The objectives of this study are to determine the level of therapeutic control of anticoagulation with vitamin K antagonists (VKA) and its possible involvement in major adverse cardiovascular events (MACE) and to evaluate differences between the group on VKA with respect to the group on DOACs.. Prospective cohort study that included consecutive patients diagnosed with NVAF in Cardiology Consultations with a clinical follow-up of 18 months. Demographic, clinical and analytical differences between groups were analyzed, including the level of therapeutic control of anticoagulation on the VKA group and its association with MACE.. Overall, 273 patients were included: 46.5% on VKA, 42.5% on DOACs, 11% without antithrombotic treatment. Patients on VKA spent 62.1% of their time within therapeutic range (TTR by the Rosendaal formule). There were no differences in MACE depending on anticoagulation control. The DOACs group presented lesser MACE rate than the VKA group (13.4 vs. 4.3%; 0.90; HR 0.90; 0.83-0.98 p = 0.01) with lower cardiovascular mortality (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) and total mortality (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p < 0.01) although without significant differences in hemorrhagic (0.9 vs. 4.7 %; p = 0.07), or ischemic events (2.6 vs. 0.8%, p = 0.27).. Patients on VKA have a different clinical profile than those who receive DOACs. Patients on VKA have an inadequate control of the anticoagulation in quite the half of the cases. The VKA group presented more MACE than the DOACs group.. La llegada de los anticoagulantes directos (ACD) ha supuesto un cambio en el tratamiento de la fibrilación auricular no valvular (FANV) en los últimos años. Los objetivos de este estudio son determinar el grado de control de la anticoagulación con antivitamina K (AVK) y su posible implicación en efectos cardiovasculares adversos mayores (ECAM) y evaluar las diferencias entre el grupo en tratamiento con AVK respecto del grupo con ACD.. Estudio de cohorte prospectivo que incluyó a pacientes consecutivos diagnosticados con FANV valorados en el Servicio de Cardiología con un seguimiento de 18 meses. Se analizaron diferencias demográficas, clínicas y analíticas entre grupos, incluido el grado de control de la anticoagulación del grupo AVK y su posible relación con ECAM.. Se incluyó a 273 pacientes: 46.5% tratados con AVK, 42.5% con ACD y 11% sin tratamiento anticoagulante. El control de la anticoagulación con AVK fue del 62.1%, sin diferencias en ECAM en función de control. El grupo ACD presentó menos ECAM que el grupo de AVK (13.4 vs. 4.3%; HR, 0.90; 0.83-0.98; p = 0.01), con una menor mortalidad cardiovascular (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) y total (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p < 0,01), aunque sin diferencias significativas en eventos hemorrágicos (0.9 vs. 4.7%; p = 0.07) ni isquémicos (2.6 vs. 0.8%; p = 0.27).. Los pacientes con AVK poseen un perfil clínico diferente en comparación con los que reciben ACD. El control de anticoagulación del grupo de AVK fue inadecuado en casi la mitad de los casos. El grupo de AVK presentó más ECAM que el grupo de ACD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Vitamin K

Atrial fibrillation (AF) is characterised by a high stroke risk. Vitamin K antagonists (VKAs) are the most commonly used oral anticoagulants (OACs) in Spain, but their efficacy and safety depend on the time in therapeutic range of International Normalized Ratio (INR) 2.0-3.0 over 65%-70%. Unfortunately, the difficulties of maintaining an optimal level of anticoagulation and the complications of VKAs (particularly haemorrhagic ones), frequently lead to cessation of this therapy, which has been associated with higher risk of adverse events (AEs), including ischaemic stroke. Our aims are as follows: (1) to evaluate the quality of oral anticoagulation with VKAs, the prevalence of poor quality of anticoagulation, and to identify factors predisposing to poor quality anticoagulation; and (2) to identify patients who will stop OAC and to investigate what factors influence the decision of OAC withdrawal.. Prospective observational cohort study including outpatients newly diagnosed with AF and naïve for OACs from July 2016 to June 2018 in an anticoagulation clinic. Patients with prosthetic heart valves, rheumatic mitral valves or valvular AF will be excluded. Follow-up will extend for up to 3 years. During this period, the INR results and changes in the anticoagulant therapy will be recorded, as well as all AEs, or any other information that would be relevant to the proper conduct of research.. All patients were informed about the nature and purpose of the study, and the protocol was approved by the Ethics Committee of Hospital General Universitario Morales Meseguer (reference: EST:20/16). This is an observational study focusing on 'real life' practice and therefore all treatments and follow-up will be performed in accordance to the routine clinical practice with no specific interventions or visits. The results of our study will be disseminated by presentations at national and international meetings, and publications in peer-reviewed journals.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; International Normalized Ratio; Observational Studies as Topic; Prospective Studies; Research Design; Spain; Stroke; Vitamin K

Atrial fibrillation is the most common cardiac arrhythmia. It increases the risk of death and thromboembolic events. Vitamin K antagonists reduce these risks. Disadvantages of vitamin K antagonist therapy are narrow therapeutic range and interactions with drugs and food. In a single center prospective study, we enrolled 249 patients with atrial fibrillation over a 12-month period. The aim of our study was to evaluate vitamin K antagonist use regarding the indication and adequate dose. Data on 249 consecutive patients with atrial fibrillation were collected before general availability of novel oral anticoagulants. Out of 249 patients, 160 (64.2%) had indication for oral anticoagulant therapy. Only 81 (50.6%) patients had vitamin K antagonist in therapy, 12 (14.8%) of them in adequate dose. We also analyzed 129 patients aged over 75, of which 109 (84.4%) had absolute indication for oral anticoagulant therapy. Only 34 (31.2%) patients aged over 75 had been receiving vitamin K antagonist therapy and 6 (17.6%) had the International Normalized Ratio values within the proposed therapeutic interval. We found a significantly higher rate of anticoagulant therapy introduction in patients under 75 years (p=0.03), but there were no significant differences in the adequacy of anticoagulant therapy (p=0.89) between these two populations. Our results showed clear inadequacies of vitamin K antagonist treatment with a growing need for a wider use of novel oral anticoagulants.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Croatia; Female; Hospitals, University; Humans; Male; Middle Aged; Prospective Studies; Thromboembolism; Vitamin K

Several comparative real-world effectiveness studies on direct oral anticoagulants (DOACs) have been conducted, but an overview of the available evidence remains to be developed, which could provide a better understanding of the value of DOACs relative to vitamin K antagonists (VKAs).. A systematic literature review was conducted on the available real-world evidence (RWE) of three DOACs (rivaroxaban, dabigatran, and apixaban) compared with VKAs (e.g. warfarin), in patients with nonvalvular atrial fibrillation (NVAF).This systematic literature review included RWE published up to December 2016. Studies with > 50 patients reporting on incident and prevalent NVAF cases were included. The following databases were searched: Medline, Embase, and the Cochrane Library. Outcomes of interest included thromboembolic events, all-cause mortality, bleeding events, and nonpersistence. Of the 562 RWE DOACs articles retrieved, 49 presented results for rivaroxaban versus VKAs, 79 for dabigatran versus VKAs, and 18 for apixaban versus VKAs. Substantial heterogeneity was found across patient population, outcome definition, and follow-up period. Major bleeding, ischemic stroke, and intracranial hemorrhage were the most frequent outcomes analyzed.. Overall, the RWE studies were aligned with the Phase 3 trials. However, conflicting results were reported for several outcomes of interest.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Vitamin K; Warfarin

Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up.. In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality.. During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI, -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3.. In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk.

Topics: Acute Disease; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; International Normalized Ratio; Male; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Spain; Survival Rate; Thromboembolism; Time Factors; Vitamin K

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Practice Patterns, Physicians'; Stroke; Vitamin K

To assess the quality of long-term anticoagulation therapy with antivitamin-K in patients with atrial fibrillation by measuring the TTR and to determine the factors associated with a good TTR.. This is an observational study conducted over a period of three years (from January 2013 until December 2015) in the outpatient clinic of cardiology of Farhat Hached hospital of Sousse, Tunisia. Pre-established individual plugs were used for data collection. The data analysis was performed using the SPSS Software, version 20.. Overall, 200 patients were eligible. Half of the patients did not know the risks of AVK and 29.1% were unaware of their interest. The average TTR was 57.3±18.2%. Good control of anticoagulation was obtained in 24.5% of patients. Those with a≥70% were more autonomous, observant, of urban origin, living in Sousse and Kairouan, with good knowledge about AVK and having a small left atrium. The factors associated negatively with TTR were hypertension, diabetes, old AF, hematological diseases, high number of medications taken daily and the presence of mitral insufficiency, mitral valve replacement, a tricuspid insufficiency or a tricuspid plasty.. The quality of AVK anticoagulation in AF patients is insufficient. Improving this indicator would reduce the morbidity and mortality associated with AVK treatment.

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Atrial Fibrillation; Diabetic Angiopathies; Female; Health Knowledge, Attitudes, Practice; Heart Valve Diseases; Hematologic Diseases; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Male; Middle Aged; Polypharmacy; Quality of Health Care; Risk Factors; Thromboembolism; Thrombolytic Therapy; Tunisia; Vitamin K

Patients with non-valvular atrial fibrillation (NVAF) have a five times higher stroke risk. For more than 50 years, vitamin K antagonists (VKAs) have been the primary medication for stroke prevention. Apixaban, a non-vitamin K oral anticoagulant (NOAC), has demonstrated better efficacy and safety characteristics than the VKA warfarin in the ARISTOTLE trial. This study aims to quantify the potential societal effects of using apixaban instead of VKA in the German NVAF population from 2017 to 2030.. Using an existing Markov model and a dynamic population approach, we modelled the health benefits of apixaban in patients with NVAF compared to VKA therapy in the German population from 2017 to 2030.. The results represent the extrapolated direct long-term health benefits of apixaban over VKA therapy for the German NVAF population. From 2017 until 2030, the use of apixaban instead of a VKA could avoid 52,185 major clinical events. This includes 15,383 non-fatal strokes or SEs, 22,483 non-fatal major bleeds, and 14,319 all-cause deaths, which correspond to 109,887 life years gained.. This study demonstrated that using apixaban instead of VKA for stroke prevention can lead to considerable reduction in cardiovascular events.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Germany; Hemorrhage; Humans; Male; Markov Chains; Models, Theoretical; Pyrazoles; Pyridones; Stroke; Time Factors; Vitamin K; Warfarin

The clinical effect of peri-operative bridging therapy in atrial fibrillation (AF) patients remains unclear given that it may increase bleeding risk without providing significant benefits. We aimed to investigate peri-procedural events in relation to peri-operative use of bridging therapy in AF patients under Vitamin K Antagonists (VKAs).. We included AF patients stable the previous 6 months on VKAs. During a median follow-up of 6.5 years (IQR 4.3-7.9), we recorded all invasive procedures and the peri-operative clinical management. All peri-procedural events (ischaemic stroke/transient ischaemic attack/systemic embolism, clinically relevant non-major bleeding and major bleeding) and severe peri-procedural events (ischaemic stroke/transient ischaemic attack/systemic embolism and major bleeding) suffered until the 30-days post-intervention period were recorded.. We included 1361 patients (48.7% male, median age 76 [IQR 71-81] years). There were 1100 (70.9%) procedures performed using bridging therapy. The rate of any (4.5% vs. 0.7%, P < 0.001) and severe (2.3% vs. 0.0%, P = 0.002) peri-procedural events were higher in patients receiving bridging therapy. Adjusted logistic regressions demonstrated that the bleeding risk of the procedure was related with higher risk of severe peri-procedural events (OR 3.51, 95% CI 1.54-8.01) and peri-procedural events (OR 2.77, 95% CI 1.56-4.91). Importantly, the use of bridging therapy was also independently associated with higher risk of any peri-procedural events (OR 4.32, 95% CI 1.28-14.51).. In this study including AF patients under VKA therapy, the use of bridging therapy as part of the clinical management during an invasive procedure was independently associated with higher risk of any peri-procedural event.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Logistic Models; Male; Perioperative Care; Prevalence; Risk Factors; Spain; Stroke; Thromboembolism; Vitamin K

We compared the 1-year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) twice daily to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation.. New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing and high-dimensional propensity score. Hazard ratios [HR (95% confidence intervals)] for stroke and systemic embolism (SSE), major bleeding (MB) and death were computed using Cox proportional hazards or Fine and Gray models during exposure.. In 14 442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA. In real life D110 and D150 were at least as effective, and safer than VKA.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Embolism; Female; Follow-Up Studies; France; Hemorrhage; Humans; Incidence; Male; Middle Aged; Prospective Studies; Stroke; Treatment Outcome; Vitamin K

Whether bleeding should be considered a sufficient sign to justify thorough cancer surveillance in atrial fibrillation (AF) patients receiving nonvitamin K antagonist oral anticoagulants (NOACs) remains unclear. We investigated the relationships between bleeding events and new-onset cancers in AF patients receiving NOACs in a prospective cohort (n = 395, mean follow-up duration of 2.8 years). There were 18 patients who were diagnosed with new-onset cancers 584 ± 372 days after the initiation of NOACs. The patients with new-onset cancers had higher HAS-BLED scores (no, preexisting and new-onset cancer: 1.51 ± 0.81, 1.69 ± 0.87, and 2.11 ± 0.96, respectively; p = 0.006) and a higher incidence of bleeding events (22%, 33%, 67%, respectively; p<0.001) than did patients without new-onset cancers. Bleeding events that preceded the diagnosis of new-onset cancers were independently correlated with new-onset cancers (odds ratio: 7.89, p = 0.001) in the multivariate logistic regression. More than half of the patients (61%) with new-onset cancers had either a significant period of drug interruption for at least 2 months or discontinued NOACs. In conclusions, bleeding in AF patients receiving NOACs could be an alerting sign of new-onset cancers and should prompt the initiation of thorough surveillance to detect early cancers.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Neoplasms; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Taiwan; Time Factors; Vitamin K

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Retrospective Studies; Thrombocytopenia; Vitamin K

Patients with atrial fibrillation generally require anticoagulant therapy and, at times, therapy with additional platelet aggregation inhibitors. Data are scarce on bleeding rates in high-risk groups receiving combination therapy, such as the elderly or patients with a high CHA. We conducted a nationwide cohort study of Danish patients with atrial fibrillation ≥50 years of age. Treatments were ascertained from a prescription database. These included no anticoagulant treatment, and treatment with vitamin K antagonists, direct oral anticoagulants, platelet inhibitors, and combinations of antithrombotic drugs. Incidence rates (IRs) of major bleeding and hazard ratios were estimated overall, and also stratified by treatment modality, age, CHA. Patients with atrial fibrillation on triple therapy experienced high rates of major bleeding in comparison with patients on dual therapy or monotherapy. The high bleeding rates observed in patients on triple therapy >90 years of age or with a CHA

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Databases, Factual; Denmark; Disease Progression; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Treatment Outcome; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies.. Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device.. In the base case, rivaroxaban saved €72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of €20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was €157/QALY.. In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Cost-Benefit Analysis; Female; Health Expenditures; Health Resources; Humans; Male; Models, Econometric; Netherlands; Prospective Studies; Rivaroxaban; Severity of Illness Index; Venous Thromboembolism; Vitamin K

The Atrial fibrillation Better Care (ABC) pathway has been proposed to streamline patient management in an integrated, holistic manner. Compliance to ABC resulted in lower incidence of cardiovascular events, but its impact on health-related costs has not been evaluated.. Exploratory analysis of costs related to cardiovascular events in the ATHERO-AF prospective cohort study including atrial fibrillation patients on vitamin K antagonists. A Diagnosis-Related Group code provided by the Italian Ministry of Health was assigned to each event to estimate the relative cost. The analysis was performed by dividing patients according to ABC pathway components.. Overall, 118 cardiovascular events incurred a cost of 1,017,354 euros (1,149,610 USD). The mean total costs were 13,050 (14,747 USD) and 11,218 euros (12,676 USD) for a non-fatal cardiac event or ischaemic stroke, respectively. The cost-saving was 719 euros (813 USD) per patient-year for patients in group A vs non-A, 703 euros (794 USD) for B vs non-B, 480 euros (542 USD) for C vs non-C and 2776 euros (3,137 USD) for ABC vs non-ABC. The cost per event increased with the number of uncontrolled ABC components: 507 euros (573 USD) for 1, 965 euros (1,091 USD) for 2 and 3,431 euros (3,877 USD) for patients not having any of the three components of the ABC.. Management of atrial fibrillation patients according to the ABC pathway was associated with significantly lower health-related costs. Application of the ABC pathway may help reduce healthcare costs related to cardiovascular events in this high-risk patient population.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cost Savings; Critical Pathways; Health Care Costs; Humans; Italy; Models, Statistical; Vitamin K

The risks of thromboembolic and hemorrhagic events in patients with atrial fibrillation both increase with age; therefore, net clinical benefit analyses of anticoagulant treatments in the elderly population are crucial to guide treatment. We evaluated the 1-year clinical outcomes with non-vitamin-K antagonist and vitamin K antagonist oral anticoagulants (NOACs vs VKAs) in elderly (≥75 years) patients with atrial fibrillation in a prospective registry setting.. Data on 3825 elderly patients were pooled from the PREFER in AF and PREFER in AF PROLONGATION registries. The primary outcome was the incidence of the net composite endpoint, including major bleeding and ischemic cardiovascular events on NOACs (n = 1556) compared with VKAs (n = 2269).. The rates of the net composite endpoint were 6.6%/year with NOACs vs 9.1%/year with VKAs (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.51-0.99; P = .042). NOAC therapy was associated with a lower rate of major bleeding compared with VKA use (OR 0.58; 95% CI, 0.38-0.90; P = .013). Ischemic events were nominally reduced too (OR 0.71; 95% CI, 0.51-1.00; P = .050). Major bleeding with NOACs was numerically lower in higher-risk patients with low body mass index (BMI; OR 0.50; 95% CI, 0.22-1.12; P = .07) or with age ≥85 years (OR 0.44; 95% CI, 0.13-1.49; P = .17).. Our real-world data indicate that, compared with VKAs, NOAC use is associated with a better net clinical benefit in elderly patients with atrial fibrillation, primarily due to lower rates of major bleeding. Major bleeding with NOACs was numerically lower also in higher-risk patients with low BMI or age ≥85 years.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Risk Factors; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Counseling; Humans; Hypertension; Interdisciplinary Communication; Obesity; Patient Education as Topic; Pharmacists; Prevalence; Professional Role; Stroke; Vitamin K

Worldwide, there is growing evidence that quality of international normalized ratio (INR) control in atrial fibrillation patients treated with Vitamin K Antagonists (VKA) is suboptimal. However, sex disparities in population-based real-world settings have been scarcely studied, as well as patterns of switching to second-line Non-VKA oral anticoagulants (NOAC). We aimed to assess the quality of INR control in atrial fibrillation patients treated with VKA in the region of Valencia, Spain, for the whole population and differencing by sex, and to identify factors associated with poor control. We also quantified switching to Non-VKA oral anticoagulants (NOAC) and we identified factors associated to switching.. This is a cross-sectional, population-based study. Information was obtained through linking different regional electronic databases. Outcome measures were Time in Therapeutic Range (TTR) and percentage of INR determinations in range (PINRR) in 2015, and percentage of switching to NOAC in 2016, for the whole population and stratified by sex.. We included 22,629 patients, 50.4% were women. Mean TTR was 62.3% for women and 63.7% for men, and PINNR was 58.3% for women and 60.1% for men (p<0.001). Considering the TTR<65% threshold, 53% of women and 49.3% of men had poor anticoagulation control (p<0.001). Women, long-term users antiplatelet users, and patients with comorbidities, visits to Emergency Department and use of alcohol were more likely to present poor INR control. 5.4% of poorly controlled patients during 2015 switched to a NOAC throughout 2016, with no sex differences.. The quality of INR control of all AF patients treated with VKA in 2015 in our Southern European region was suboptimal, and women were at a higher risk of poor INR control. This reflects sex disparities in care, and programs for improving the quality of oral anticoagulation should incorporate the gender perspective. Clinical inertia may be lying behind the observed low rates of switching in patient with poor INR control.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Drug Substitution; Female; Humans; International Normalized Ratio; Male; Middle Aged; Sex Factors; Spain; Vitamin K

Atrial fibrillation (AF) is present in 15-20% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke.. In April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany.. Overall, 154 stroke unit leads participated (response rate 52%). Anticoagulation in the acute phase of stroke is considered feasible in more than 90% of AF patients with ischemic stroke. Clinicians assume that about two thirds of all AF patients (range 20-100%) are discharged on oral anticoagulation. According to local preferences, acetylsalicylic acid is given orally in the majority of patients with delayed initiation of oral anticoagulation. A non-vitamin K-dependent oral anticoagulant (NOAC) is more often prescribed than a vitamin K-dependent oral anticoagulant (VKA). VKA is more often chosen in patients with previous VKA intake than in VKA naive patients. In the minority of patients, stroke unit leads discuss the prescription of a specific oral anticoagulant with the treating general practitioner. Adherence to medical stroke prevention after hospital discharge is not assessed on a regular basis in any patient by the majority of participating stroke centers.. Early secondary stroke prevention in AF patients in German stroke units is based on OAC use but prescription modalities vary in clinical practice.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cross-Sectional Studies; Female; Germany; Humans; Male; Middle Aged; Recurrence; Risk Factors; Secondary Prevention; Stroke; Vitamin K

Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs.. In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations.. We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use.. In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.

Topics: Administration, Oral; Aged; Anticoagulants; Asian People; Atrial Fibrillation; Dabigatran; Drug Labeling; Female; Humans; Male; Medication Adherence; Middle Aged; Prospective Studies; Pyrazoles; Pyridines; Pyridones; Republic of Korea; Risk Factors; Rivaroxaban; Thiazoles; Vitamin K

Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events.. This study compared the long-term efficacy and safety of apixaban with that of uninterrupted vitamin K antagonist (VKA) therapy in patients with AF scheduled for transesophageal echocardiogram (TEE)-guided direct current cardioversion (DCC) from June 2014 to September 2016.. We enrolled consecutive patients with persistent nonvalvular AF scheduled to undergo DCC. Patients received apixaban 5 mg or 2.5 mg twice daily (bid) or VKA at therapeutic doses for at least 3 weeks before and 4 weeks after DCC. All patients underwent anamnestic, clinical, electrocardiographic, and echocardiographic evaluation at each follow-up visit and were followed-up for 12 months. The primary efficacy endpoint was the composite of stroke/transient ischemic attack and systemic embolism. The primary safety endpoint was major bleeding.. After propensity score matching, comparative treatment groups comprised 182 (75.8%) patients receiving apixaban 5 mg bid and 182 receiving VKA. A low incidence of atrial thrombus (0.5%) at TEE was found in both groups. The acute cardioversion success rate was 86.1% in the apixaban group (156/181) and 83.9% in the VKA group (152/181). During the follow-up period, a similarly low incidence of thromboembolic events (1.1%) was reported in both groups; the bleeding safety profile tended to favor apixaban over VKA (1.1 vs. 1.6%; p = 0.3).. Newly initiated anticoagulation with apixaban in patients with nonvalvular AF scheduled for TEE-guided DCC seems to be as effective and safe as uninterrupted VKA therapy during 12 months of follow-up.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Propensity Score; Prospective Studies; Pyrazoles; Pyridones; Stroke; Thromboembolism; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Humans; Patients; Vitamin K

Topics: Atrial Fibrillation; Dabigatran; Humans; Pyrazoles; Pyridones; Rivaroxaban; Vitamin K

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Topics: Algorithms; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Renal Dialysis; Secondary Prevention; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

Previous studies indicated low-intensity warfarin (INR target of 1.5-2.5) achieved reduced hemorrhage without increasing thromboembolism for Asians with non-valvular atrial fibrillation (NVAF). Whether non-vitamin K antagonist oral anticoagulant (NOAC) is superior to warfarin with good time in the therapeutic range (TTR) based on lower INR target among Asians with NVAF remains unknown.. In this retrospective study collected from Taiwan Chang Gung Memorial Hospital Database, there were 5,197, 3,396, and 9,898 consecutive patients taking warfarin, NOAC, and no-treatment, respectively, from January 1, 2000 to December 31, 2015. Propensity-score weighting was used across the study groups. Patients were followed until the first occurrence of study outcome or end date of study.. Among those patients taking warfarin, the mean"artificial" TTR (aTTR) based on a lower INR target of 1.5-2.5 was 44.4±33.3%. Total 79.2% (n = 2,690) patients took low-dose NOACs. Patients with aTTR in the range from <30%(34.0%), 30-50%(17.6%), 50-70%(23.5%) to >70%(24.9%) showed decremental risks of efficacy and composite outcome compared with no-treatment. The risk of major bleeding didn't increase among patients with top aTTR>70% compared to no-treatment. The NOAC group showed a comparable risk of composite outcome to the warfarin subgroup with aTTR of >70% (P = 0.485). The NOAC group had a lower risk of composite outcome than warfarin subgroup with TTR of>70% based on the INR target of 2.0-3.0 (P = 0.004).. NOACs showed a comparable risk of efficacy, safety, and composite outcome to well-managed warfarin based on a lower INR target of 1.5-2.5 in Asians with NVAF taking oral anticoagulants.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Taiwan; Thromboembolism; Vitamin K; Warfarin

Combination of dual antiplatelet (DAPT) and oral anticoagulation therapy is required to decrease cardioembolic stroke and stent thrombosis risk in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). We compared the safety and efficacy of dabigatran etexilate with vitamin K antagonist (VKA), in combination with DAPT (aspirin plus clopidogrel) treatment in AF patients who underwent percutaneous coronary intervention (PCI) with stenting for ACS.. Consecutive nonvalvular AF patients who received twice-daily dabigatran 110 mg (n = 389) or VKA (n = 510) and DAPT were included. Primary endpoints were major bleeding (safety) and the composite of ischemic stroke, systemic embolism, and myocardial infarction (efficacy). The secondary efficacy endpoint was hospitalization for cardiovascular disease.. After propensity score matching, comparative treatment groups comprised 175 dabigatran recipients and 175 VKA recipients. The cumulative incidence of major bleeding was lower in the dabigatran group (2.3%) compared with the VKA group (10.3%) with a hazard ratio (HR) of 4.81 [95% confidence interval (CI) 1.6-14.2,. Dabigatran at the dose used for stroke prevention appears safer than VKA and maintains a similar efficacy profile, when used with DAPT, in AF patients who have undergone PCI with stenting for ACS.

Topics: Aged; Atrial Fibrillation; Dabigatran; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Pilot Projects; Probability; Propensity Score; Thromboembolism; Treatment Outcome; Vitamin K

 This study assessed changes in anticoagulation therapy over time in patients with atrial fibrillation (AF)..  Analyses were performed on a claims-based dataset of 4 million health-insured individuals. The study population consisted of patients newly initiating a non-vitamin-K oral anticoagulants (NOACs) or vitamin K antagonist (VKA) for AF between 2013 and 2016. The study outcomes consisted of the proportion of patients who had (1) discontinued OAC treatment, (2) switched from VKA to NOAC, (3) switched from NOAC to VKA or (4) switched from one NOAC to another. Predictors of discontinuation or switching of OAC treatment were determined by Cox proportional hazards regression models with time-independent and time-dependent covariates..  The study population comprised 51,606 AF patients initiating VKA (.  Overall discontinuation rates of VKA and NOACs are comparable over the first year of therapy, while switching from VKA to NOAC was more common than from NOAC to VKA. The majority of treatment changes were associated with clinical events.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Drug Substitution; Female; Follow-Up Studies; Germany; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Vitamin K; Withholding Treatment

Geriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56-0.87) to 0.73 (95% CI, 0.60-0.89) for the geriatric groups and 0.71 (95% CI, 0.56-0.93) to 0.76 (0.59-0.98) for the non-geriatric groups (

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Geriatrics; Germany; Humans; Middle Aged; Phenprocoumon; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Vitamin K

In the treatment of non-valvular atrial fibrillation (AF) with oral anticoagulants (OAC), medical adherence is a relevant factor for stroke prevention.. To evaluate the one-year persistence of vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC) in patients suffering from AF and already treated with OACs.. Information from the National Health Insurance Fund of Hungary prescriptions database on pharmacy claims between June 1, 2015 and December 31, 2015 was analysed. Authors identified patients who filled prescriptions for OACs (VKAs or DOACs) prescribed for AF who have already received OACs therapy during one year before. Apparatus of survival analysis was used, where 'survival' was the time to abandon the medication.. 196 016 patients met the inclusion criteria. 181 810 patients received VKA and 14 206 patients were treated with DOACs. The one-year persistence rate in patients taking VKA was 52.9% whereas it was 66.8% in those on the DOACs. The persistence rates after 360 days were 67.5% for rivaroxaban, 63.6% for apixaban and 63.4% for dabigatran. The mean duration of persistence was 311 days for rivaroxaban, 308 days for apixaban and 284 days for dabigatran. The actual rate of discontinuation was 14% (HR = 1.14 [95% CI 1.05-1.24]), p = 0.0015) for apixaban, 15% (HR = 1.15 [95% CI 1.08-1.23], p = 0.003) for dabigatran and 62% (HR = 1.62 [95% CI 1.56-1.69], p<0.0001) for VKA compared to rivaroxaban (reference).. The authors have confirmed that the one-year persistence of DOAKs was significantly higher compared to KVA therapy in AF. The one-year persistence of rivaroxaban was more favoured than apixaban and dabigatran. Orv Hetil. 2019; 160(13): 509-515.. Absztrakt: Bevezetés: A nonvalvularis pitvarfibrilláció (PF) orális antikoagulánssal (OAK) történő kezelésekor a terápiahűség igen jelentős tényező a stroke prevenciójában. Célkitűzések: A szerzők célja a már OAK-terápiában részesülő PF-ban szenvedő betegeknél a K-vitamin-antagonista (KVA) és a direkt orális antikoagulánsok (DOAK) egyéves perzisztenciájának vizsgálata. Módszer: A Nemzeti Egészségbiztosítási Alapkezelő adatbázisából a vényforgalmi adatokra támaszkodva pitvarfibrilláció indikációjában, 2015 második félévében valamely orális antikoaguláns (OAK = KVA/DOAK) receptjét kiváltó olyan betegeket választottak ki, akiknek a vizsgálati időszakot megelőzően – a vizsgálati időszakban történt kiváltási dátumhoz képest – 12 hónappal korábban volt (DOAK/KVA összes) vénykiváltásuk. A perzisztencia modellezésére a túlélés-analízis klasszikus eszköztárát alkalmazták, ahol a „túlélési” idő a gyógyszer szedésének abbahagyásáig eltelt idő volt, 60 napos ’grace’ periódussal. Eredmények: A bevonási kritériumoknak 196 016 beteg felelt meg. A betegek közül 181 810 szedett KVA-t, míg 14 206 beteg kapott DOAK-ot. A KVA-k egyéves perzisztenciája 52,9%, a DOAK-ot szedőké 66,8% volt. A DOAK-terápián belül a rivaroxaban egyéves perzisztenciája 67,5%, az apixabané 63,6%, a dabigatrané 63,4% volt. A 360 napra korlátozott átlagos gyógyszerszedési idő 311 nap volt a rivaroxaban, 308 nap az apixaban, 303 nap a dabigatran, míg 284 nap a KVA-k esetén. A gyógyszerelhagyás kockázatának pillanatnyi rátája az apixaban esetén 14%-kal (HR = 1,14 [95% CI 1,05–1,24]), p = 0,0015), a dabigatrannál 15%-kal (HR = 1,15 [95% CI 1,08–1,23], p = 0,003), a KVA-t szedőknél 62%-kal (HR = 1,62 [95% CI 1,56–1,69], p<0,0001) volt magasabb a rivaroxabanhoz képest. Következtetés: A szerzők igazolták, hogy PF-ban a KVA-terápiához képest a DOAK-ok egyéves perzisztenciája szignifikánsan magasabb volt. A DOAK-ok közül a rivaroxaban egyéves perzisztenciája előnyösebbnek bizonyult az apixabanhoz és a dabigatranhoz képest. Orv Hetil. 2019; 160(13): 509–515.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Humans; Hungary; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Vitamin K

To investigate the risk of stroke/thromboembolism (TE) and major bleeding associated with anaemia among patients with atrial fibrillation (AF). Also, to assess the effects of oral anticoagulation (OAC) and time in therapeutic range (TTR) with vitamin K antagonists according to level of haemoglobin (Hb).. Through administrative registry databases, we identified all Danish patients diagnosed with AF from 1997 to 2012. We included 18 734 AF patients with recent available data on Hb. Multiple Cox regression analyses were used to estimate hazard ratios and to compute standardized absolute 1-year risks of stroke/TE and major bleeding. Among included patients, 3796 (20%) had mild anaemia (Hb 6.83-7.45 mmol/L for women and Hb 6.83-8.03 mmol/L for men) and 2562 (14%) had moderate/severe anaemia (Hb <6.83 mmol/L). Moderate/severe anaemia was associated with increased risk of major bleeding and 9.1% lower median TTR compared with no anaemia. Use of OAC was associated with reduced risk of stroke/TE among patients without anaemia [standardized absolute 1-year difference -2.5%, 95% confidence interval (CI) -3.8 to -1.7%] or with mild anaemia (-2.3%, 95% CI -2.8 to -1.8%), but not with moderate/severe anaemia, (0.03%, -1.8 to +2.8%, interaction P = 0.01). Oral anticoagulation was associated with a 5.3% (95% CI 2.1-8.7%) increased standardized absolute risk of major bleeding among AF patients with moderate/severe anaemia.. Anaemia was common in patients with AF and associated with major bleeding and lower TTR. Oral anticoagulation was associated with more major bleeding, but no reduction in risk of stroke/TE among AF patients with moderate/severe anaemia.

Topics: Aged; Aged, 80 and over; Anemia; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Hemorrhage; Humans; Male; Proportional Hazards Models; Stroke; Thromboembolism; Vitamin K

The incidence of intracerebral hemorrhage (ICH) in patients using oral anticoagulation (OAC) will continue to increase with the demographic change of an aging population. As compared to primary spontaneous ICH, OAC-ICH is characterized by larger hematoma volumes, more frequent hematoma enlargement and intraventricular hemorrhage resulting in an even worse prognosis. Specific treatment should focus on immediate reversal of anticoagulation in addition to the basic acute management of ICH. In ICH patients using vitamin K antagonists (VKA), complete anticoagulant reversal with an international normalized ratio (INR) <1.3 should be achieved as quickly as possible using prothrombin complex concentrate (PCC) with additional substitution of vitamin K. Patients with ICH under dabigatran treatment should receive idarucizumab. In ICH patients using factor-Xa inhibitors, andexanet should be administered as soon as approved in Europe or within clinical studies and if unavailable alternatively high-dose PCC administration. Regarding OAC resumption, results from randomized trials are pending. In comprehensive observational studies and meta-analyses ICH patients resuming OAC showed a reduced incidence of thromboembolic events and mortality without significantly increased rates of hemorrhagic complications. Non-vitamin K dependent oral anticoagulants (NOAC) might further increase the safety of OAC resumption, which should be initiated after 4-8 weeks for patients with atrial fibrillation. In contrast, VKA resumption in patients with mechanical heart valves should not take place earlier than 1 week after ICH. Generally, safety of OAC resumption appears to be affected by ICH localization along with the presence of cerebral microbleeding, cortical superficial siderosis and cortical/convexity subarachnoid hemorrhage, making it crucial to weigh up the individual patient risk with respect to thromboembolic versus hemorrhagic events.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Europe; Humans; Randomized Controlled Trials as Topic; Vitamin K

For patients with atrial fibrillation (AF) receiving cardiac implantable electronic device (CIED) implantations, current consensus recommends uninterrupted non-vitamin K antagonist oral anticoagulant (NOAC) considering low incidence of bleeding or thrombo-embolic events. It remains unknown whether uninterrupted strategy outweighs discontinuation method for patients receiving NOAC.. From January 1, 2013 to June 1, 2017, we enrolled 100 patients (mean age 78.3 ± 10.2 years, 58% male) with AF taking NOAC for stroke prevention eligible for CIED implantation in a tertiary medical center, Taipei, Taiwan. NOAC was continued without skipping any doses during the surgery. The baseline characteristics, underlying diseases, CHA2DS2-VASc score, and clinical course of every patient were reviewed and analyzed.. Among these patients, 28 were on dabigatran, 61 on rivaroxaban, 10 on apixaban, and one on edoxaban, respectively. There were no adverse events except one case of pericardial effusion and another one with large pocket hematoma. One patient receiving implantable cardioverter defibrillator implantation had late onset of pericardial effusion with impending tamponade necessitating pericardiocentesis. Another patient had large pocket hematoma, which spontaneously resolved within 1 month without further intervention. No periprocedural mortality and stroke occurred.. Uninterrupted NOAC during CIED implantations may be an acceptable option especially in patients with high risk for thromboembolism. However, special caution should be paid during defibrillator implantation considering relatively higher risk of bleeding, perhaps due to the larger size of the defibrillator lead.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Defibrillators, Implantable; Female; Humans; Male; Pacemaker, Artificial; Vitamin K

We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.. We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).. We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09).. DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Stroke; Vitamin K

AVK could be prescribed in elderly patients over 75 years for the prevention of thromboembolic complications of atrial fibrillation (AF). The objective of this study was to study the quality of the anticoagulation balance by AVK and its determinants. Inclusion of all patients ≥ 75 years of age treated with AVK for an AF hospitalized in the acute geriatric department of the University hospital of Dijon. The balance of the AVK treatment was determined by the input INR and the calculation of the TTR. The last four INRs prior to admission were retrospectively collected for its calculation. Each patient had a standardized geriatric evaluation (EGS): lifestyle, MMSE, nutritional status (albumin), polypathology (Charlson), level of dependence (ADL-IADL). Bleeding complication were collected. 155 patients aged over 75 years (87±5.6 years, 88 women and 67 men) were included. The mean TTR was 55.4±31.2%. Only 46% of patients had a correct TTR (≥ 75%). The balance was significantly worse in women than in men (49.3±29.5 vs 60.1±31.8%; p=0.0326), and in case of haematological pathology (41.7±27.1 vs 57.2± 9.8; p=0.047) but better with high BMI (r=0.416, p=0.001). No EGS parameters were associated with the quality of anticoagulation. The control of AVK therapy is insufficient in geriatric elderly subjects. No modifiable explicative geriatric factor has been identified. If AVK remains a therapeutic option, direct oral anticoaulants should be considered as the first choice.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Geriatric Assessment; Hemorrhage; Hospitalization; Humans; International Normalized Ratio; Life Style; Longitudinal Studies; Male; Nutritional Status; Retrospective Studies; Sex Characteristics; Thromboembolism; Vitamin K

Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months.. This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups.. The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs.. This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Incidence; Intracranial Hemorrhages; Japan; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Prospective Studies; Recurrence; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

To describe (i) the trend in oral anticoagulant (OAC) use following the introduction of non-vitamin K antagonist oral anticoagulant (NOAC) therapy for stroke prevention in atrial fibrillation (AF) patients and (ii) the current patterns of use of NOAC therapy in new users with AF in France.. (i) Repeated cross-sectional study and (ii) population-based cohort study.. French national healthcare databases (50 million beneficiaries).. (i) Patients with identified AF in 2011, 2013 and 2016 and (ii) patients with AF initiating OAC therapy in 2015-2016. PRIMARY AND SECONDARY OUTCOME MEASURES: (i) Trend in OAC therapy use in patients with AF and (ii) patterns of use of NOAC therapy in new users with AF.. Between 2011 and 2016, use of OAC therapy moderately increased (+16%), while use of antiplatelet therapy decreased (-22%) among all patients with identified AF. In 2016, among the 1.1 million AF patients, 66% used OAC therapy and were more likely to be treated by vitamin K antagonist (VKA) than NOAC therapy, including patients at higher risk of stroke (63.5%), while 33% used antiplatelet therapy. Among 192 851 new users of OAC therapy in 2015-2016 with identified AF, NOAC therapy (66.3%) was initiated more frequently than VKA therapy, including in patients at higher risk of stroke (57.8%). Reduced doses were prescribed in 40% of NOAC new users. Several situations of inappropriate use at NOAC initiation were identified, including concomitant use of drugs increasing the risk of bleeding (one in three new users) and potential NOAC underdosing.. OAC therapy use in patients with AF remains suboptimal 4 years after the introduction of NOACs for stroke prevention in France and improvement in appropriate prescribing regarding NOAC initiation is needed. However, NOAC therapy is now the preferred drug class for initiation of OAC therapy in patients with AF, including in patients at higher risk of stroke.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Cross-Sectional Studies; Databases, Factual; Drug Utilization; Female; France; Humans; Male; Middle Aged; Stroke; Time Factors; Vitamin K; Young Adult

Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications.. We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy, including any therapeutic switching among DOACs. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression.. Naïve patients initiating direct oral anticoagulants for stroke prevention in NVAF identified in a 4.25-year period are 17,920. After one year, the persistence to the DOACs is 72.9%. Approximately 9.8% of the discontinuations are due to switch to vitamin k antagonists (VKAs). On multivariate analysis, factors negatively affecting persistence were female gender, age <65 years, renal disease and history of bleeding. On the other hand, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction.. In this study of real world data, one out four naive patients stopped treatment with DOACs within 12 months. Some characteristics may identify patients with poor persistence.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Italy; Male; Middle Aged; Population Surveillance; Retrospective Studies; Stroke; Survival Rate; Treatment Outcome; Vitamin K; Warfarin; Young Adult

In Italy, direct oral anticoagulant drugs (DOACs) were authorized for stroke prevention in\ patients with non-valvular atrial fibrillation (NVAF) in 2013. There is conflicting evidence on their benefit-risk profile under real world conditions.. The Italian Medicines Agency funded this study to investigate effectiveness and safety of DOACs compared to vitamin K antagonists (VKAs) in three Italian regions. An observational study was conducted with a sequential propensity-score-matched\ new user parallel-cohort design in the period July 2013-December 2015 using administrative health data. DOAC users with NVAF diagnosis were 1:1 matched to VKA users based on a PS which accounted for over 90 potential confounders at baseline. Applying an as-treated approach with a 90-day renewal grace time, patients were followed from the day after the first prescription of the study drug until occurrence of the outcome, death, discontinuation, switch, end of health plan enrolment, or study end. Outcomes were total and cardiovascular mortality, acute myocardial infarction, ischemic and haemorrhagic stroke, and gastrointestinal bleeding. Analyses were performed, using\ Cox proportional hazard models stratified by matched set. The results of the regional analyses were combined through a random-effects meta-analysis.. During the first 30 months of authorisation for NVAF, DOACs were increasingly prescribed. Overall, 72,434 new anticoagulant users were enrolled, 34% of whom received a DOAC. After PS matching, 37,266 patients contributed to the analysis.\ No differences between the study groups were found for total and cardiovascular mortality, myocardial infarction and ischemic stroke. DOAC users were at higher risk of\ gastrointestinal bleeding (HR 1.41, 95%CI 1.07-1.86) and at a not significant lower risk of haemorrhagic stroke (HR 0.36, 95%CI 0.10-1.33).. The present study confirms findings from previous research regarding bleeding events, whereas we did not find a reduced risk of mortality in DOAC users. Further research on single active agents and specific populations is warranted.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Practice Patterns, Physicians'; Stroke; Vitamin K

Lack of INR controls might affect the adherence to direct oral anticoagulants (DOAC). The vast majority of studies that addresses adherence to anticoagulants are retrospective and based on pharmacy refill data. Our aim was to compare the adherence between vitamin K antagonists (VKA) and DOAC and to analyze the clinical relevance of non-adherence.. A prospective two-arm observational cohort study was performed in two Spanish public hospitals. Adherence was assessed by Medication Event Monitoring System. Relationship between adherence and events during follow-up and time in therapeutic range (TTR) in the VKA group were analyzed.. 257 patients were included (132 DOAC and 125 VKA). Monitoring time was 120 days (101-133). Patients in VKA group showed higher taking adherence (97.9% vs. 95.8%) and less non-adherent patients of >5% and >10% of the doses, without differences in >20% of the doses. Taking adherence was strongly associated with TTR (AUC: 0.89, CI 95%: 0.81-0.97 of TTR for detection of non-adherent patients of >10% of doses). During a follow-up of 1.8 years (1.6-2) non-adherent patients of >5% of doses presented more thromboembolic events (HR 6.1, CI95% 1.3-28.1).. Although adherence to oral anticoagulant therapy was excellent, it was higher to VKA than to DOAC. Time in therapeutic range was highly sensitive to few missed doses of AVK. Non-adherence of >5% of prescribed doses had high clinical relevance.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; Male; Prospective Studies; Vitamin K

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Kidney Function Tests; Male; Republic of Korea; Retrospective Studies; Risk Factors; Stroke; Vitamin K

A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored.. Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ± antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016.. The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP.. GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Stroke; Vitamin K

The purpose of the current study was to compare the efficacy and safety of edoxaban versus vitamin K antagonist (VKA) therapy among a cohort of elderly patients (ie, those aged ≥75 years) with atrial fibrillation (AF) in a real-life setting.. A propensity score-matched cohort observational study was performed comparing the safety and efficacy of edoxaban versus VKA therapy among a cohort of elderly (aged ≥75 years) patients with AF in a real-life setting. Follow-up data were obtained through outpatient visits at 1, 3, and every 6 months. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack, and systemic embolism.. A total of 130 patients receiving edoxaban 60 mg (EDO) treatment were compared with the same number of VKA recipients. The mean follow-up was 16 (2.6) months. The cumulative incidence of thromboembolic events in the EDO and VKA groups was 1.5% (2 of 130) and 2.3% (3 of 130), respectively (P < 0.6). The cumulative incidence of major bleeding events was 1.5% (2 of 130) in the EDO group and 3.1% (4 of 130) in the VKA group (P < 0.4). The total anticoagulant therapy discontinuation rate was 2.3% (3 of 130) in the EDO group and 4.6% (6 of 130) in the VKA group (P < 0.3). A nonsignificant trend in improved adherence was observed between the EDO and VKA groups (81% vs 78%; P = 0.6).. Edoxaban therapy showed a good real-life performance among elderly patients (aged ≥75 years) with AF.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cohort Studies; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Propensity Score; Pyridines; Stroke; Thiazoles; Thromboembolism; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Pyridines; Thiazoles; Vitamin K

Triple antithrombotic therapy (TT) is recommended for patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, there is a lack of comparative data in a real-world clinical setting between non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists (VKA). The aim of this study was to compare the safety and efficacy of TT with NOAC or VKA after PCI in patients with AF at 1-year of follow-up.. This was an observational retrospective study in 2 tertiary care hospitals during 2013-2016. Patients with indication for anticoagulation due to AF from an initial registry of 5,269 patients undergoing PCI were identified. Safety primary endpoint was the occurrence of major bleeding events as defined by Bleeding Academic Consortium (BARC ≥ 3). The primary efficacy endpoint was defined as major adverse cardiovascular events (MACE).. A total of 187 consecutive patients on TT were identified: 45.4% of were discharged on NOAC and 54.6% on VKA. Patients who received VKA presented more comorbidities and had a higher bleeding risk than those who received NOACs. Major bleeding events occurred in 17 patients (9%), with a higher rate in the VKA group (3.5% vs. 13% confidence interval, 0.19-0.86, P = 0.02). There were no differences in the rates of major adverse cardiovascular events, stroke or net clinical benefit.. In this real-world study, patients with AF undergoing PCI treated on NOAC-based TT showed lower bleeding rates than those on VKA, with a lower rate of major bleeding events, while efficacy was similar between groups.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Male; Percutaneous Coronary Intervention; Retrospective Studies; Vitamin K

The purpose of the study was to investigate the impact of oral anticoagulation (OAC) type on clinical outcomes 1 year after transcatheter aortic valve replacement (TAVR).. Non-vitamin K oral anticoagulants (NOACs) are superior to vitamin K antagonists (VKAs) in nonvalvular atrial fibrillation (AF), while their comparative performance among patients in need of OAC undergoing TAVR is underinvestigated.. The study enrolled 962 consecutive patients who underwent TAVR in 4 tertiary European centers and were discharged on either NOACs (n = 326) or VKAs (n = 636). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding.. Mean age and Society of Thoracic Surgeons score of the population were 81.3 ± 6.3 years and 4.5% (interquartile range: 3.0% to 7.3%); 52.5% were women and a balloon-expandable valve was used in 62.7% of cases. The primary outcome of interest, combined incidence of all-cause mortality, myocardial infarction, and any cerebrovascular event at 1-year after TAVR, was 21.2% with NOACs versus 15.0% with VKAs (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.00 to 2.07; p = 0.050, IPTW-adjusted). The 1-year incidence of any Bleeding Academic Research Consortium bleeds and all-cause mortality were comparable between the NOAC and VKA groups, 33.9% versus 34.1% (HR: 0.97; 95% CI: 0.74 to 1.26; p = 0.838, IPTW-adjusted) and 16.5% versus 12.2% (HR: 1.36; 95% CI: 0.90 to 2.06; p = 0.136, IPTW-adjusted), respectively.. Chronic use of both NOACs and VKAs among patients in need of OAC after TAVR are comparable regarding 1-year bleeding risk. The higher ischemic event rate observed with NOACs needs to be evaluated in large randomized trials.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve Stenosis; Atrial Fibrillation; Europe; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Registries; Risk Assessment; Risk Factors; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Balance between embolic and bleeding risk is challenging among patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. We further evaluated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with cancer.. The AMBER-AF registry is an observational multicentre study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain. 1,237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. Mean follow-up was 3.1 years. Both groups were similar in age, embolic risk and bleeding risk. Lack of guidelines-recommended therapies was more frequent among patients with cancer. Compared with patients without cancer, adjusted rates of stroke (hazard ratio [95% confidence interval]) in cancer patients were higher (1.56 [1.04-2.35]), whereas bleeding rates remained similar (1.25 [0.95-1.64]). Within the group of patients with cancer, the use of DOACs vs VKAs did not entail differences in the adjusted rates of stroke (0.91 [0.42-1.99]) or severe bleedings (1.53 [0.93-2.53]).. Antithrombotic management of AF frequently differs in patients with breast cancer. While breast cancer is associated with a higher risk of incident stroke, bleeding events remained similar. Patients with cancer treated with DOACs experienced similar rates of stroke and bleeding as those with VKAs.

Topics: 4-Hydroxycoumarins; Aged; Anticoagulants; Atrial Fibrillation; Breast Neoplasms; Female; Hemorrhage; Humans; Incidence; Indenes; Middle Aged; Proportional Hazards Models; Stroke; Treatment Outcome; Vitamin K

The oral anticoagulant warfarin is a vitamin K antagonist and is considered the first line anticoagulant in valvular atrial fibrillation. However prothrombin time should be closely monitored, drug interactions checked and compliance regarding diet ensured when the patient is on warfarin therapy. Anaemia should be looked for, evaluated for the cause and corrected since it is an independent predictor of bleeding and thrombotic episodes during warfarin therapy for atrial fibrillation We present an interesting case of anaemia which developed during warfarin therapy for atrial fibrillation. The patient was on amiodarone and was consuming leafy vegetables resulting in frequent raise in prothrombin time during which time she developed bleeding into the right femoral pseudoaneurysm which had developed following catheterisation for thrombectomy. Surgical correction of pseudoaneurysm was done, comedication was changed and diet compliance ensured which resulted in the subsequent maintenance of prothrombin time in the therapeutic range and steady haemoglobin levels.

Topics: Anemia; Aneurysm, False; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Directive Counseling; Female; Humans; Middle Aged; Prothrombin Time; Spinacia oleracea; Treatment Outcome; Vitamin K; Warfarin

Studies from several countries show that self-management of vitamin K antagonist (e.g., warfarin) therapy reduce the risk of complications compared with conventional management.. The aim of this study was to investigate the quality of warfarin management when patients were transferred from conventional management to self-management in Norway. In addition, quality of life (QoL) before and after 2 years of warfarin self-management was investigated.. The study was longitudinal with a retrospective and prospective design where 126 patients on conventional management of long-term warfarin therapy underwent a 21-week training program of warfarin self-management followed by 2 years of self-management. The outcomes of the study were time in therapeutic range (TTR), the variance of international normalized ratio (INR) values, extreme INR values (INR ≤ 1.5 and ≥ 5), complications, and QoL, comparing the 2-year period of the conventional management with the 2-year period with the self-management.. The median TTR was higher during self-management compared with conventional management (78.1% vs. 65.9%, respectively,. We used five different measures and found improved quality of warfarin self-management 2 years after patients were transferred from the conventional management.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Drug Monitoring; Female; Heart Valve Prosthesis; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Patient Education as Topic; Prospective Studies; Quality of Life; Retrospective Studies; Self-Management; Venous Thromboembolism; Vitamin K; Warfarin

Scarce data comparing real-world outcomes between apixaban and vitamin K antagonist (VKA) users with nonvalvular atrial fibrillation (NVAF) are available. We sought to assess the effectiveness and safety of newly-initiated apixaban vs. VKA in German NVAF patients.. We performed a retrospective analysis in German outpatients using IMS Disease Analyzer data. Adults newly-initiated on apixaban or a VKA from January 2013 to March 2015 with a diagnosis of NVAF on the day of the first qualifying oral anticoagulant (OAC) prescription (index date) or any time during 1 year prior, and at least 1 year of follow-up were included. Patients experiencing a prior event in the composite endpoint, receiving an OAC before the index date, >1 OAC on the index date or switched to another OAC during follow-up were excluded. Apixaban and VKA users were 1:1 propensity-score matched. We evaluated the composite of ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) or intracranial haemorrhage (ICH) in the year after OAC initiation. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).. In total, 835 apixaban and 835 VKA users were matched. Forty-one composite events were identified. Hazard of the composite endpoint did not differ between apixaban and VKA users (HR=0.87, 95%CI=0.47-1.60). Ischaemic stroke and MI occurred at dissimilar (albeit not statistically significant) rates between apixaban and VKA therapy (HR=1.51, 95%CI=0.54-4.24) and (HR=0.33, 95%CI=0.11-1.03). Only two patients (both in the apixaban cohort) experienced an ICH.. Apixaban and VKA therapy were associated with a similar impact on the composite endpoint in real-world German practice. Additional investigation is needed to evaluate the numeric trends of ischaemic stroke and decreased number of MIs observed with apixaban, as well as the high rate of reduced dose apixaban use found in this analysis.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Propensity Score; Pyrazoles; Pyridones; Retrospective Studies; Stroke; Treatment Outcome; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used as thromboembolic prophylaxis in cardioversion. We examined the waiting time to cardioversion and the outcomes in patients with non-valvular atrial fibrillation (AF) of > 48 h of duration who were treated with either NOACs or warfarin.. Anticoagulation was handled in a structured, multidisciplinary AF-clinic. The objectives were the waiting time to cardioversion, and thromboembolism and major bleeding events within 60 days. In total, 2150 electrical cardioversions were performed; 684 (31.8%) of patients were on NOACs and 1466 (68.2%) were on warfarin. The waiting time to non-TOE-guided cardioversion was significantly shorter in the NOAC group compared with the warfarin group for all cardioversions (P < 0.001 for log-rank test) and for first-time cardioversions (P < 0.001 for log-rank test). For all non-TOE-guided cardioversions, 80% of procedures on NOACs and 67% of procedures on warfarin were performed within 25 days (P < 0.001). Thromboembolism occurred in one patient (0.15%) receiving NOAC and in two patients (0.14%) receiving warfarin (risk ratio (RR) 1.07; 95% confidence interval (CI) 0.10-11.81). Major bleeding events occurred in four patients (0.58%) in the NOAC group and 11 patients (0.75%) in the warfarin group (RR 0.78; 95% CI 0.25-2.43).. In a real-world clinical setting with anticoagulation handled in a structured multidisciplinary AF clinic, the waiting time to cardioversion was shorter with NOACs compared to warfarin. The rates of thromboembolism and major bleeding events were low, with NOACs shown to be as effective and safe as warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke; Thromboembolism; Time Factors; Time-to-Treatment; Treatment Outcome; Vitamin K; Warfarin

After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran, rivaroxaban, or apixaban) has not been quantified, and could help assess whether these drugs are used according to recommendations.. Using Danish nationwide registries, we identified all VKA-experienced NVAF patients initiating a NOAC from 22 August 2011 to 31 December 2015 (shifters) and all VKA-experienced NVAF patients who were not switched to NOACs (non-shifters). Baseline characteristics and temporal utilization trends were examined. We included 62 065 patients with NVAF; of these, 19 386 (29.6%) shifted from a VKA to a NOAC (9973 (54.2%) shifted to dabigatran, 4775 (26.0%) to rivaroxaban, and 3638 (19.8%) to apixaban). Shifting was associated with lower age [odds ratio (OR) 0.95, 95% confidence interval (95% CI) 0.94-0.96 per 5 year increments], female gender (OR 1.33, 95% CI 1.28-1.38), and certain co-morbidities: more often stroke, bleeding, heart failure, and alcohol abuse, and less often hypertension, ischaemic heart disease, and diabetes. Shifting was common and initially dominated by shifting from VKA to dabigatran, but at the end of 2015, most shifters were shifted to rivaroxaban (45%) or apixaban (45%) whereas shifting to dabigatran decreased (to 10%).. In a contemporary setting among VKA-experienced NVAF patients; VKA is still prevalent although about 30% by December 2015 had shifted to a NOAC.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Denmark; Drug Substitution; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Registries; Rivaroxaban; Stroke; Vitamin K

Atrial fibrillation (AF) causes a significant health and economic burden to the Dutch society. Dabigatran was proven to have at least similar efficacy and a similar or better safety profile when compared to vitamin K antagonists (VKAs) in preventing arterial thromboembolism in patients with AF.. To evaluate the cost-effectiveness and monetary benefit of dabigatran vs VKAs in Dutch patients with non-valvular AF. Value-based pricing considerations and corresponding negotiations on dabigatran will be explicitly considered.. The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the RE-LY trial and Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed.. Dabigatran was cost saving compared to VKAs. A total of 4,552 QALYs were gained, and €13,892,288 was saved in a cohort of 10,000 AF patients. The economic value of dabigatran was strongly related to the costs of VKA control that are averted. Notably, dabigatran was cost saving compared to VKAs if annual costs of VKA control exceeded €159 per person, or dabigatran costs were below €2.81 per day.. Dabigatran was cost saving compared to VKAs for the prevention of atrial thromboembolism in patients with non-valvular AF in the Netherlands. This result appeared robust in the sensitivity analysis. Furthermore, volume based reduction of the price in the Netherlands will further increase the monetary benefits of dabigatran.

Topics: Antithrombins; Atrial Fibrillation; Cohort Studies; Cost-Benefit Analysis; Dabigatran; Female; Humans; Male; Markov Chains; Netherlands; Quality-Adjusted Life Years; Retrospective Studies; Risk Assessment; Thromboembolism; Treatment Outcome; Vitamin K

Atrial fibrillation (AF)-European guidelines suggest the use of biomarkers to stratify patients for stroke and bleeding risks. We investigated if a multibiomarker strategy improved the predictive performance of CHA. We included consecutive patients stabilized for six months on vitamin K antagonists (INRs 2.0-3.0). High sensitivity troponin T, NT-proBNP, interleukin-6, von Willebrand factor concentrations and glomerular filtration rate (eGFR; using MDRD-4 formula) were quantified at baseline. Time in therapeutic range (TTR) was recorded at six months after inclusion. Patients were follow-up during a median of 2375 (IQR 1564-2887) days and all adverse events were recorded.. In 1361 patients, adding four blood biomarkers, TTR and MDRD-eGFR, the predictive value of CHA. Addition of biomarkers enhanced the predictive value of CHA

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cardiovascular Diseases; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Interleukin-6; International Normalized Ratio; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Stroke; Troponin T; Vitamin K; von Willebrand Factor

Non-vitamin K antagonist oral anticoagulants (NOACs) are being introduced for stroke prevention in non-valvular Atrial Fibrillation (AF), and promise to be accepted better than Vitamin K Antagonists (VKAs) by patients, improving their Quality of Life (QoL).. To assess to what extent patient-related factors influence decisions to switch from a VKA to a NOAC.. The PREFER in AF Registry collected data at baseline in 2012 - at the beginning of NOAC prescriptions - and at 1-year follow-up, in 6412 patients in seven Western European countries. QoL and patient satisfaction questionnaires (EQ-5D-5L and/or PACT-Q2) were completed in 3777 patients at both visits. Data were compared across categories of patients on stable treatment with a VKA (i.e. continuously over the previous 12 months) (n=2102) or recently switched (within 12 months) from a VKA to a NOAC (n=213) during a 1-year follow-up, allowing a snapshot of factors influencing the switch at a time when NOACs were being introduced into the market.. At the beginning of NOAC prescriptions, European doctors tended to switch from VKAs to NOACs those patients at lower risk than "non-switchers". Complaints about bruising or bleeding, dissatisfaction with treatment, mobility problems and anxiety/depression traits appear to be related to - and may have influenced - the choice to switch from a VKA to a NOAC.

Topics: Activities of Daily Living; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Drug Substitution; Europe; Female; Follow-Up Studies; Health Status; Humans; Male; Middle Aged; Patient Satisfaction; Quality of Life; Registries; Risk Factors; Stroke; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vitamin K

The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment.. We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and cause-specific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use.. Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score ≤1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score ≥2 was not associated with an increased mortality risk after adjustment.. Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Assessment; Risk Factors; Stroke; Survival Rate; Vitamin K

Direct oral anticoagulants (DOACs) have been proposed as a more convenient alternative to vitamin K antagonists (VKAs), which are commonly associated with poor treatment persistence in non-valvular atrial fibrillation (nv-AF).. Using data from the French national health care databases (Régime Général, 50 million beneficiaries), a cohort study was conducted to compare the 1-year non-persistence rates in nv-AF patients initiating dabigatran (N=11,141) or rivaroxaban (N=11,126) versus VKA (N=11,998). Treatment discontinuation was defined as a switch between oral anticoagulant (OAC) classes or a 60-day gap with no medication coverage, with the additional criterion of no reimbursement for international normalized ratio monitoring during this gap for VKA patients. Considering death as a competing risk, differences between 1-year discontinuation rates were used to compare each DOAC versus VKA. The 95% confidence intervals (CIs) were estimated via bootstrapping. Baseline patient characteristics were adjusted using inverse probability of treatment weighting. Subgroup analyses considered DOAC dose at initiation, age, risk of stroke, and bleeding.. Adjusted 1-year discontinuation rates were higher for dabigatran than for VKA new users (36.8% vs 30.2%; difference: 6.6% [95% CI, 5.5-7.6]) and for rivaroxaban versus VKA new users (33.4% vs 30.4%; 3.0% [1.9-4.1]). Similar differences were found in all subgroup analyses, except in dabigatran and rivaroxaban patients <75 years (dabigatran vs VKA: 0.3% [-1.4 to 1.8]; rivaroxaban vs VKA: -2.6% [-4.3 to -0.9]) and dabigatran 150 mg new users (-1.1% [-3.1 to 0.7]). Consistent results were obtained when considering both switches between OAC classes and death as competing risks of treatment discontinuation.. Results from this nationwide cohort study showed high non-persistence levels with all OACs and suggest that persistence with both dabigatran and rivaroxaban therapy is not better than persistence with VKA therapy. Hospitalizations for bleeding among non-persistent patients were unlikely to explain these high non-persistence rates.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Databases, Factual; Dose-Response Relationship, Drug; Female; France; Hemorrhage; Hospitalization; Humans; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Rivaroxaban; Stroke; Vitamin K

To investigate temporal trends in the use of non-vitamin K oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in combination with aspirin and/or clopidogrel in patients with atrial fibrillation (AF) following acute myocardial infarction (MI) and/or percutaneous coronary intervention (PCI).. Using Danish nationwide registries, all patients with AF who survived 30 days after discharge from MI and/or PCI between 22 August 2011 and 30 September 2016 were identified.. From 2011 to 2016, the use of NOAC in combination with antiplatelet(s) increased in patients with AF following MI/PCI and exceeded the use of VKA in combination with antiplatelet(s) by 2016.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Denmark; Drug Therapy, Combination; Female; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Retrospective Studies; Treatment Outcome; Vitamin K

The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA.. Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021).. In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Humans; International Normalized Ratio; Male; Odds Ratio; Peripheral Arterial Disease; Prevalence; Prospective Studies; Registries; Risk Factors; Spain; Stroke; Vitamin K

Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA.. Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years.. Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%.. NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Monitoring; Female; Germany; Hemorrhage; Humans; Kidney Diseases; Male; Nursing Homes; Phenprocoumon; Rivaroxaban; Stroke; Vitamin K

We examined the risks of all-cause mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists (VKAs) and non-VKAs oral anticoagulants (NOACs) following traumatic injury in atrial fibrillation (AF) patients.. This was a Danish nationwide registry-based study (2005-16), including 4541 oral anticoagulant (OAC)-treated AF patients experiencing traumatic injury (defined as traumatic brain injury, hip fracture, or traumatic torso or abdominal injury). Within 90 days following discharge from traumatic injury, 60.6% resumed VKA (median age = 80, CHA2DS2-VASc = 4, HAS-BLED = 2), 16.7% resumed NOAC (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 2), and 22.7% did not resume OAC treatment (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 3). Switch from VKA to NOAC occurred among 9.5%. Since 2009, the trend in OAC resumption increased (P-value <0.0001), in particular with NOACs (P-value <0.0001). Follow-up started 90 days after discharge, and time-varying multiple Cox regression analyses were used for comparisons. Compared with non-resumption, VKA and NOAC resumption were associated with lower hazard [95% confidence interval (CI)] of all-cause mortality [hazard ratio (HR) 0.48 (0.42-0.53) and HR 0.55 (0.47-0.66), respectively] and ischaemic stroke [HR 0.56 (0.43-0.72) and HR 0.54 (0.35-0.82), respectively], increased major bleeding hazard [HR 1.30 (1.03-1.64) and HR 1.15 (0.81-1.63), respectively], and similar hazard of recurrent traumatic injury [HR 0.93 (0.73-1.18) and HR 0.87 (0.60-1.27), respectively].. AF patients resuming VKA and NOAC treatment following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury. Withholding OAC following a traumatic injury in AF patients may not be warranted.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Female; Hemorrhage; Humans; Male; Recurrence; Registries; Retrospective Studies; Risk Factors; Stroke; Thrombosis; Vitamin K; Wounds and Injuries

Clinicians struggle daily with the optimal regimen for patients with an indication for antiplatelet therapy after stenting and in patients needing oral anticoagulation treatment for atrial fibrillation (AF). This is not only difficult in patients with acute coronary syndrome (ACS) but also in the large number of patients with AF undergoing elective percutaneous coronary intervention (PCI). The challenge is to strike a balance between the increasing risk of bleeding events and ischemic or thrombotic events. Until recently, guidelines were based on expert consensus and a few small, many of them retrospective, trials. A so-called triple therapy with a vitamin K antagonist (VKA) and dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended for patients with AF undergoing PCI in stable coronary artery disease or for those with ACS. However, severe bleeding complications remain a major issue during triple therapy, particularly in the growing aging population. In the past year, randomized controlled trials (RCT) with direct-acting oral anticoagulants (DOACs) have modified the standard use of care, now favoring dual therapy with DOACs. This review elucidates the current influential RCTs on the new antiplatelet and anticoagulation strategies for patients with AF undergoing PCI or with ACS, and discusses whether triple therapy is still required.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Guideline Adherence; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Factors; Stents; Stroke; Thrombosis; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Veterans; Vitamin K; Warfarin

Atrial fibrillation (AF) is the most common arrhythmia worldwide, and its prevalence is expected to increase with population ageing. The use of vitamin K antagonists (VKAs) for the prevention of stroke and/or systemic embolism in patients with non-valvular atrial fibrillation (NVAF) was recently challenged by non-VKA oral anticoagulants (NOACs), demonstrating a favourable risk-benefit profile, with reductions in stroke, intracranial haemorrhage and mortality, similar major bleeding, but increased gastrointestinal bleeding. Nevertheless, data on their use in a "real-life" setting are scarce for France.. To compare the characteristics of patients with AF newly anticoagulated with either VKAs or NOACs, to describe the reasons for discontinuing the previous anticoagulant strategy and/or choosing the newly initiated anticoagulant treatment, and to precisely describe the prescriptions of patients newly initiated with apixaban.. This is a nationwide multicentre non-interventional cross-sectional study conducted in patients with AF by a representative stratified sample of cardiologists in France. Over a 12-month accrual period, consecutive patients aged ≥18 years with NVAF, for whom anticoagulant treatment (VKAs or NOACs) has been initiated within the last three months before the index consultation, will be included. The primary outcome will be the comparison of anticoagulant-naïve patient characteristics, co-morbidities and treatment history among the anticoagulant subgroups. Secondary endpoints will include a description of the reasons for discontinuing the previous anticoagulant strategy and/or for initiating and choosing the newly initiated anticoagulant treatment, as well as the prescription conditions of apixaban.. The PAROS study will provide real-life data on the characteristics of NVAF patients and their anticoagulant prescription in France.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Drug Prescriptions; Drug Substitution; Embolism; Factor Xa Inhibitors; France; Hemorrhage; Humans; Pyrazoles; Pyridones; Research Design; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Vitamin K

Patients with atrial fibrillation (AF) are predisposed to a hypercoagulable state and are at an increased risk for thromboembolic events when undergoing procedures. This study investigated the long-term efficacy and safety of newly initiated anticoagulation with dabigatran versus uninterrupted vitamin K antagonist (VKA) therapy in patients with AF scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC). Consecutive adult patients with persistent AF scheduled to undergo DCC were included in the study. Patients received dabigatran 110 mg or 150 mg twice daily (bid) or VKA at therapeutic doses for at least 3 weeks before and 4 weeks after DCC. All patients underwent anamnestic, clinical, electrocardiographic and echocardiographic evaluation at each follow-up visit, and were followed up for a total period of 2 years. The primary efficacy outcome was the composite of stroke/transient ischaemic attack and systemic embolism. The primary safety outcome was major bleeding. 176 patients receiving dabigatran (77% dabigatran 150 mg bid) were propensity score-matched to 176 patients on VKA therapy. A low incidence of atrial thrombus (0.6%) at TEE was found in both groups (0.6%). The acute cardioversion success rate was 85.1% in the dabigatran group (149/175) and 83.4% in the VKA group (146/175). During the follow-up period, a similar low incidence of thromboembolic events (0.6%) was reported in both groups; the bleeding safety profile tended to favour dabigatran over VKA (1.1% vs 1.7%; P = 0.3). Newly initiated anticoagulation with dabigatran in patients with nonvalvular AF scheduled for TEE-guided DCC seems to be as effective and safe as uninterrupted VKA therapy, during long-term follow up.

Topics: Adult; Aged; Atrial Fibrillation; Cohort Studies; Dabigatran; Echocardiography, Transesophageal; Electric Countershock; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Propensity Score; Prospective Studies; Thromboembolism; Treatment Outcome; Vitamin K

Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS. Clinical variables, CHADS2-VASC score and data about the international normalized ratio (INR) within the therapeutic range were all recorded. DNA was extracted from blood and genotyping was carried out by DNA sequencing. The main endpoint was the time from VKA onset to IS. Of a total of 356 consecutive IS patients monitored, 33 were included in the study. The median time to the event was 2248.0 days (interquartile range [IQR] 896.3-3545.3). The median CHADS2-VASC score was 4.0 (IQR 3.0-6.0). When we considered the risk of IS within 2 years under VKA treatment, we found that only the rs2108622 AA genotype was significantly associated with this endpoint (early IS) (hazard ratio 6.81, 95% CI 1.37-33.92, p = 0.019). Kaplan-Meier curve analysis also showed a significant relationship between early IS and rs2108622 AA genotype (Log rank p = 0.022). The CYP4F2 gene rs2108622 polymorphism was associated with a risk of early IS in NV-AF patients under VKA treatment.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 4; Female; Genotype; Humans; International Normalized Ratio; Male; Polymorphism, Single Nucleotide; Prospective Studies; Risk Assessment; Stroke; Vitamin K; Vitamin K Epoxide Reductases

Essentials Acute coronary syndrome (ACS) with atrial fibrillation (AF) is a therapeutic challenge. Dual and triple antithrombotic therapy showed a similar thrombotic risk in ACS patients with AF. The omission of aspirin during the first month did not increase the rate of ischemic events. Replacement of vitamin K antagonist by dabigatran leads to an increased thrombotic risk.. Background Dual antithrombotic therapy comprising a vitamin K antagonist (VKA) plus clopidogrel reduces the incidence of major bleeding compared with triple therapy (VKA + clopidogrel + aspirin) in acute coronary syndrome (ACS) patients with atrial fibrillation (AF), with a similar thrombotic risk. The oral thrombin inhibitor dabigatran (150 mg twice a day) showed superiority over VKA in non-valvular AF, but data supporting its use in AF patients presenting with ACS are limited. Objective We sought to evaluate the efficacy of dabigatran vs. VKA in the management of AF patients undergoing percutaneous coronary intervention for an ACS. Methods In this open-label study, 133 consecutive patients received dabigatran plus clopidogrel. Another cohort of 133 patients treated with VKA plus clopidogrel was used as the control group. Results After propensity score adjustment, the cumulative incidence of major adverse cardiovascular events over 24 months was higher with dabigatran vs. VKA (adjusted hazard ratio, 2.28; 95% confidence interval, 1.46-3.56). Similar rates of major bleeding were found (adjusted hazard ratio, 1.17; 95% confidence interval, 0.46-2.96). Conclusions In AF patients presenting with ACS, replacement of VKA by dabigatran concurrently with clopidogrel is associated with an increased thrombotic risk, without a reduction in major bleeding.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Blood Platelets; Clopidogrel; Cohort Studies; Coronary Angiography; Dabigatran; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Incidence; Ischemia; Kaplan-Meier Estimate; Male; Middle Aged; Outcome Assessment, Health Care; Patient Safety; Phenindione; Propensity Score; Proportional Hazards Models; Risk; Treatment Outcome; Vitamin K

The efficacy and tolerability of vitamin K antagonists (VKAs) depends on the quality of anticoagulant control, reflected by the mean time in therapeutic range (TTR) of international normalized ratio 2.0 to 3.0. In the present study, we aimed to investigate the association between TTR and change in TTR (ΔTTR) with the risk of mortality and clinically significant events in a consecutive cohort of atrial fibrillation (AF) patients.. We included 1361 AF patients stable on VKAs (international normalized ratio 2.0-3.0) during at least the previous 6 months. After 6 months of follow-up we recalculated TTR, calculated ΔTTR (ie, the difference between baseline and 6-month TTRs) and investigated the association of both with the risk of mortality and "clinically significant events" (defined as the composite of stroke or systemic embolism, major bleeding, acute coronary syndrome, acute heart failure, and all-cause deaths).. The median ΔTTR at 6 months of entry was 20% (interquartile range 0-34%), 796 (58.5%) patients had a TTR reduction of at least 20%, while 330 (24.2%) had a TTR <65%. During follow-up, 34 (2.5% [4.16% per year]) patients died and 61 (4.5% [7.47% per year]) had a clinically significant event. Median ΔTTR was significantly higher in patients who died (35.5% vs 20%; P = 0.002) or sustained clinically significant events (28% vs 20%; P = 0.022). Based on Cox regression analyses, the overall risk of mortality at 6 months for each decrease point in TTR was 1.02 (95% CI, 1.01-1.04; P = 0.003), and the risk of clinically significant events was 1.01 (95% CI, 1.00-1.03; P = 0.028). Patients with TTR <65% at 6 months had higher risk of mortality (hazard ratio = 2.96; 95% CI, 1.51-5.81; P = 0.002) and clinically significant events (hazard ratio = 1.71; 95% CI, 1.01-2.88; P = 0.046).. Our findings suggest that in AF patients anticoagulated with VKAs, a change in TTR over 6 months (ie, ΔTTR) is an independent risk factor for mortality and clinically significant events. Even in a cohort with good anticoagulation control, the risk for mortality and clinically significant events increases with every point deterioration of TTR.

Topics: Acenocoumarol; Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Regression Analysis; Risk Factors; Stroke; Vitamin K

Topics: Administration, Intravenous; Aged; Anticoagulants; Atrial Fibrillation; Brain; Emergency Service, Hospital; Factor V; Factor Xa; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Paresis; Plasma; Tomography, X-Ray Computed; Vitamin K; Warfarin

This is an observational study to investigate the efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with bioprosthetic valves or prior surgical valve repair in clinical practice. A total of 122 patients (mean age: 74.1 ± 13.2; 54 females) with bioprosthetic heart valve or surgical valve repair and AF treated with NOACs were included in the analysis. The mean CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Male; Middle Aged; Registries; Vitamin K

Vitamin K antagonists (VKAs) remain the mainstay of anticoagulation therapy, which requires monitoring of international normalised ratio (INR). Quality of oral anticoagulation, clinical benefits, and the risk related to VKA use are determined by the time in therapeutic range (TTR).. The aim of this study was to assess the therapeutic quality of oral anticoagulation and to determine the factors that affect the incidence of INR outside the recommended range in primary care patients undergoing long-term VKA therapy in Poland.. A multi-centre cross-sectional analysis was carried out in 15 general practices from three voivodeships of Poland. At the planned time, INRs measured closest to the designated date in all patients were assessed in terms of being within the therapeutic range. TTR was determined as the percentage of visits with INR in therapeutic range on a given date.. Overall, 430 patients aged 70.3 ± 12.7 years (222 men aged 72 ± 12.8 years and 208 women aged 68.5 ± 12.4 years) were included in the study. In the groups with INR below, within, and above therapeutic range, the patients' age was 67.3 ± 13.4, 72 ± 12, and 70.5 ± 13 years (p = 0.001), respectively. TTR for all the participants was 55%. Statistically significant factors associated with INRs outside the therapeutic range were: age below 60 years (compared to older persons; p = 0.003), more or less frequent INR control compared to the recommended intervals of four to eight weeks (p < 0.001), and the type of the VKA used, i.e. acenocoumarol compared to warfarin (p < 0.001). Logarithmic regression analysis showed that the use of acenocoumarol compared to warfarin, increased the chances of INRs below therapeutic range (odds ratio [OR] 3.19; 95% confidence interval [Cl] 1.65-6.16), while male sex increased the probability of INR being above this range (OR 2.01; 95% Cl 1.12- 3.59).. The TTR in primary care patients on VKA therapy was 55%. Better quality of oral anticoagulation with VKA could be achieved by using warfarin instead of acenocoumarol, proper INR monitoring in the recommended interval of four to eight weeks, and tighter INR control in younger and male patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cross-Sectional Studies; Disease Management; Female; Fibrinolytic Agents; Humans; International Normalized Ratio; Male; Middle Aged; Poland; Primary Health Care; Quality Control; Vitamin K; Warfarin

To investigate evolving patterns in antithrombotic treatment in UK patients with newly diagnosed non-valvular atrial fibrillation (AF).. Prospective, multicentre, international registry.. 186 primary care practices in the UK.. 3482 participants prospectively enrolled in four sequential cohorts (cohort 2 (C2) n=830, diagnosed September 2011 to April 2013; cohort 3 (C3) n=902, diagnosed April 2013 to June 2014; cohort 4 (C4) n=850, diagnosed July 2014 to June 2015; cohort 5 (C5) n=900, diagnosed June 2015 to July 2016). Participants had newly diagnosed non-valvular AF and at least one risk factor for stroke, were aged ≥18, and provided informed consent.. 42.7% were women and the mean age was 74.5 years. The median CHA. There has been a progressive increase in the proportion of patients newly diagnosed with AF receiving guideline-recommended therapy in the UK, potentially driven by the availability of NOACs.. NCT01090362; Pre-results.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Protocols; Female; Fibrinolytic Agents; Guideline Adherence; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stroke; United Kingdom; Vitamin K

Atrial fibrillation (AF) is common in patients with heart failure and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in out-patients with AF, it remains unclear whether DOACs reduce mortality in hospitalized heart failure (HHF) patients with AF. Therefore, we examined the impact of DOACs on mortality in this group of patients.. Consecutive 497 HHF patients with AF were retrospectively registered and divided into three groups on the basis of the presence of anticoagulant therapy: non-anticoagulant group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n = 150). We followed up all the patients for mortality.. In the Kaplan-Meier analysis (mean follow-up of 1093 days), all-cause mortality was significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and 15.3% vs. 43.3%, log-rank P < 0.001). In the multivariable Cox proportional hazard analysis after adjusting for other potential confounding factors, usage of DOACs and VKAs were independently associated with lower mortality in HHF patients AF (DOACs, HR 0.356, P = 0.001; VKAs, HR 0.472, P = 0.002). Furthermore, the propensity-matched 1:1 cohort was assessed based on the propensity score (DOACs, n = 114 and VKAs, n = 114). All-cause mortality was significantly lower in the DOACs group than in the VKAs group in the post-matched cohort (12.3% vs. 35.1%, log-rank P = 0.038). In the Cox proportional hazard analysis, the use of DOACs was associated with lower mortality in the post-matched cohort (HR 0.526, P = 0.041).. Appropriate use of anticoagulants in HHF patients with AF is important, and DOACs potentially improve all-cause mortality in such patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Chi-Square Distribution; Comorbidity; Female; Heart Failure; Hospitalization; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Prevalence; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin K

To evaluate the effectiveness and safety of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) among patients with non-valvular atrial fibrillation (NVAF), particularly those with chronic kidney disease (CKD).. Population-based matched cohort study.. Over 670 primary care practices in the UK, contributing to the Clinical Practice Research Datalink.. Up to 6818 adult patients newly treated with NOACs between 2011 and 2016, matched 1:1 to new users of VKAs on age, sex and high-dimensional propensity score.. Current exposure to NOACs compared with current exposure to VKAs.. HRs of ischaemic stroke and systemic embolism (SE), major bleeding, gastrointestinal (GI) bleeding, intracranial bleeding, myocardial infarction and all-cause mortality.. In as-treated analyses, the rates of ischaemic stroke/SE were similar between NOACs and VKAs (HR 0.94; 95% CI 0.62 to 1.42), as were the rates of major bleeding (HR 0.86; 95% CI 0.56 to 1.33). NOACs also significantly increased the risk of GI bleeding (HR 1.78; 95% CI 1.27 to 2.48). In patients with NVAF and CKD, NOACs and VKAs remained comparable with respect to the risk of ischaemic stroke/SE (HR 0.79; 95% CI 0.40 to 1.58) and major bleeding (HR 0.88; 95% CI 0.47 to 1.62), with no difference in the risk of GI bleeding (HR 0.99; 95% CI 0.63 to 1.55). Similar results were obtained in on-treatment analyses using a time-dependent exposure definition.. Our results suggest that in the UK primary care, NOACs are overall effective and safe alternatives to VKAs, among patients with NVAF altogether, as well as in patients with NVAF and CKD.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Primary Health Care; Regression Analysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; United Kingdom; Vitamin K; Young Adult

In summary, uninterrupted oral antikoagulation can be recommended, with different recommendation classes and levels of evidence, for both, VKA and NOAC therapy, in the framework of PVI. Even with low CHA

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Austria; Catheter Ablation; Drug Administration Schedule; Humans; Pulmonary Veins; Stroke; Vitamin K

This study evaluated the safety and efficacy of venous figure-of-eight (FoE) suture to achieve femoral venous hemostasis after radiofrequency (RF) catheter ablation (CA) for atrial fibrillation (AF).Methods and Results:We retrospectively examined 517 consecutive patients undergoing RFCA for AF. The control group (n=247) underwent manual compression for femoral venous hemostasis after sheath removal with 6 h of bed rest. The FoE group (n=270) underwent FoE suture technique with 4 h of bed rest. All patients achieved successful hemostasis within 24 h after CA. Although the incidence of hematoma was similar between the groups, the incidence of rebleeding was lower in the FoE group than in the control group (FoE vs. control, 3.7% vs. 18.6%, P<0.001). The post-procedural use of analgesic and/or anti-emetic agents was less frequent in the FoE group (19.3% vs. 32.0%, P<0.001). On multiple logistic regression analysis after adjustment for age and sex, the use of a vitamin K antagonist (OR, 2.42; 95% CI: 1.18-4.99, P=0.02) and the FoE suture technique (OR, 0.17; 95% CI: 0.08-0.35, P<0.001) were independent predictors of rebleeding after CA.. FoE suture technique effectively achieved femoral venous hemostasis after RFCA for AF. It reduced the risk of rebleeding, shortened bed rest duration, and relieved patient discomfort.

Topics: Aged; Analgesics; Atrial Fibrillation; Bed Rest; Case-Control Studies; Catheter Ablation; Female; Femoral Vein; Hematoma; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Retrospective Studies; Suture Techniques; Treatment Outcome; Vitamin K

Clinical trials and subsequent meta-analyses showed advantages of non-vitamin K antagonists oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation. The impact of preadmission anticoagulation in acute ischaemic stroke (AIS) has not been established.. To compare functional outcome of patients with AIS with preadmission NOACs vs. VKAs.. A retrospective analysis was conducted on consecutive AIS patients under oral anticoagulation (VKAs or NOACs) admitted in 4 Portuguese hospitals within a period of 30 months. Two primary outcomes were defined and compared between VKA and NOAC groups: symptomatic intracerebral hemorrhage transformation (sICH) and modified Rankin Scale (mRS) at 3 months.. Four hundred sixty-nine patients were included, of whom 332 (70.8%) were treated with VKA and 137 (29.2%) with NOAC. Patients' median age was 78.0 and 234 (49.9%) were male. NOAC-treated patients had a higher median CHA2DS2-VASc score than those under VKA (5.0 vs. 4.0, p = 0.023). The two primary outcomes showed no statistical differences between the VKAs' group and the NOACs' group (sICH: 5.4 vs. 5.4% [p = 0.911]; mRS at 3 months: 3.0 vs. 3.0 [p = 0.646], respectively).. Preadmission anticoagulation with NOACs in AIS has a functional impact similar to that of VKAs.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Portugal; Retrospective Studies; Stroke; Treatment Outcome; Vitamin K

Anticoagulation control in patients with atrial fibrillation (AF) has a multidisciplinary approach although is usually managed by general practitioners (GP) or haematologists. The aim of our study was to assess the quality of anticoagulation control with vitamin K antagonists (VKAs) in relation to the responsible specialist in a "real-world" AF population.. We consecutively enrolled VKA anticoagulated patients included in the FANTASIIA Registry from 2013 to 2015. We analysed demographical, clinical characteristics and the quality of anticoagulation control according to the specialist responsible (ie GPs or haematologists).. Data on 1584 patients were included (42.5% females, mean age 74.0 ± 9.4 years): 977 (61.7%) patients were controlled by GPs and 607 (38.3%) by haematologists. Patients managed by GPs had higher previous heart disease (53.2% vs 43.3%, P < .001), heart failure (32.9% vs 26.5%, P < .008) and dilated cardiomyopathy (15.2% vs 8.7%, P < .001) with better renal function (69.3 ± 24.7 vs 63.1 ± 21.4 mL/min, P < .001) compared to patients managed by haematologists. There was no difference between groups in the type of AF, CHA. About 60% of AF patients anticoagulated with VKAs had poor anticoagulation control (ie TTR<70%), and their management was only slightly better than when it is managed by general practitioners.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Dilated; Electric Countershock; Female; General Practice; Heart Failure; Hematology; Humans; Kidney; Male; Prospective Studies; Quality of Health Care; Registries; Risk Factors; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Humans; Stroke; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; Vitamin K

The aim of this study is to compare discontinuation risk and health care resource utilization between vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs) in newly treated patients with non-valvular atrial fibrillation (NVAF). Based on administrative databases of five Italian Local Healthcare Units, all patients with a discharge diagnosis of NVAF between 2011 and 2014 were selected. Among them, the incident users of NOACs and VKAs in 2014 were followed-up to from the first prescription date to the occurrence of anyone of the following events: a 90-day gap in therapy, switch to a different molecule or add-on of a different molecule into the regimen, death of patient, end of follow-up (December 2015). All-cause hospitalizations, outpatient visits and examinations within the persistence period were also evaluated. The final cohort was composed of 2909 and 765 incident users of VKA and NOACs, respectively. Cox regression\ to model time to non-persistence within 12 months showed a 62% reduction in risk of drug discontinuation in NOAC patients compared to VKA patients (HR,0.38 [0.33-0.44]). In the adjusted analyses with warfarin as reference, apixaban patients (HR, 0.35 [0.24-0.50]) had the lowest risk of non-persistence, followed by rivaroxoban (HR, 0.42 [0.33-0.54]) and dabigatran users (HR, 0.51 [0.43-0.61]). The mean total numbers of all-cause hospitalization records in 12-month persistent patients were significantly less in NOACs users compared with VKA users (0.36 vs 0.47, p-value:0.03). Similarly, the differences in the mean numbers of all-cause visits and examinations were statistically significant between VKA and NOAC patients, who\ registered on average 2.33 vs 1.84 visits (p-value: 0.01) and 24.4 vs 9.2 exams referrals (p-value: <0.0001), respectively.\ NOACs showed a better profile in terms of both resource utilization and persistence compared with VKAs. In particular, apixaban returned the lowest risk of discontinuation than dabigatran and rivaroxaban.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Databases, Factual; Female; Follow-Up Studies; Health Resources; Hospitalization; Humans; Italy; Male; Medication Adherence; Middle Aged; Proportional Hazards Models; Retrospective Studies; Time Factors; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are relatively new drugs used for stroke prevention in nonvalvular atrial fibrillation (NVAF). However, there are concerns that their use may be associated with hepatotoxic effects.. The purpose of this study was to determine whether the use of NOACs is associated with an increased risk of serious liver injury compared with the use of vitamin K antagonists (VKAs) in NVAF patients with and without prior liver disease.. Using the administrative databases of the Canadian province of Quebec's health insurances, the authors conducted a cohort study among patients newly diagnosed with NVAF between January 2011 and December 2014. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of serious liver injury (defined as either a hospitalization or related death) were estimated using time-dependent Cox proportional hazards models, comparing current use of NOACs to current use of VKAs separately among patients with or without prior liver disease.. The cohort comprised 51,887 patients, including 3,778 with prior liver disease. During 68,739 person-years of follow-up, 585 patients experienced a serious liver injury. Compared with current use of VKAs, current use of NOACs was not associated with an increased risk of serious liver injury in patients without or with prior liver disease (adjusted HR: 0.99; 95% CI: 0.68 to 1.45; and adjusted HR: 0.68; 95% CI: 0.33 to 1.37, respectively).. Compared with VKAs, NOACs were not associated with an increased risk of serious liver injury irrespective of baseline liver status. Overall, these results provide reassurance regarding the hepatic safety of NOACs.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Canada; Chemical and Drug Induced Liver Injury; Cohort Studies; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Liver; Liver Function Tests; Male; Middle Aged; Risk Adjustment; Stroke; Vitamin K

To determine the preventability of serious adverse drug reactions (ADRs) related to the use of direct oral anticoagulants (DOACs), and to explore contributing factors to preventable ADRs. Results were compared with vitamin K antagonists (VKAs).. We conducted a prospective observational study in the emergency departments of two teaching hospitals from July 2015 to January 2016. Patients admitted with a thrombotic or bleeding event while under DOAC or VKA were included. Four independent reviewers assessed causality, seriousness and preventability of ADRs using pilot-tested scales. For cases of serious and potentially preventable ADRs, we performed semi-structured interviews with general practitioners to identify contributing factors to ADRs. The primary outcome was the proportion of serious ADRs that were potentially preventable.. The analysis included 46 DOAC and 43 VKA patients (median age 79 years). Gastrointestinal (n = 34) and intracranial (n = 16) bleedings were the most frequent ADRs. Results were that 53% of DOAC- and 61% of VKA-related serious ADRs were deemed potentially preventable. Prescribing issues and inadequate monitoring were frequent for DOAC and VKA respectively. We identified many causes of preventable ADRs that applied to all oral anticoagulants, such as pharmacodynamic drug interactions and lack of communication.. More than half of serious ADRs were potentially preventable for both DOACs and VKAs. Interventions focusing on prescribing, patient education and continuity of care should help improve the use of DOACs in practice.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Continuity of Patient Care; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Male; Patient Education as Topic; Prospective Studies; Stroke; Thromboembolism; Vitamin K

Real-time monitoring is used to the ends of postmarketing observational research on newly marketed drugs. We implemented a pilot near-real-time monitoring program on the test case of oral anticoagulants. Specifically, we evaluated the safety and effectiveness of direct oral anticoagulants compared to vitamin K antagonists in nonvalvular atrial fibrillation secondary prevention during 2013-2015 in the Lazio Region, Italy.. A cohort study was conducted using a sequential propensity-score-matched new user parallel-cohort design. Sequential analyses were performed using Cox models. Overall, 10 742 patients contributed to the analyses. Compared with vitamin K antagonists, direct oral anticoagulant use was associated with a reduction of all-cause mortality (0.81; 95% confidence interval [CI] 0.66-0.99), cardiovascular mortality (0.71; 95% CI 0.54-0.93), myocardial infarction (0.67; 95% CI 0.43-1.04), ischemic stroke (0.87; 95% CI 0.52-1.45), hemorrhagic stroke (0.25; 95% CI 0.07-0.88), and with a nonsignificant increase of gastrointestinal bleeding (1.26; 95% CI 0.69-2.30).. The present pilot study is a cornerstone to develop real-time monitoring for new drugs in our region.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cause of Death; Comparative Effectiveness Research; Databases, Factual; Hemorrhage; Humans; Italy; Pilot Projects; Predictive Value of Tests; Product Surveillance, Postmarketing; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Time Factors; Treatment Outcome; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with atrial fibrillation (AF) worldwide. Few articles have compared current understanding of AF patients about the disease and anticoagulant therapy in relation to the medications used.. We sought to compare the knowledge of AF and anticoagulation between AF patients treated with NOACs and those on vitamin K antagonists (VKAs).. We used the Jessa AF Knowledge Questionnaire (JAKQ), developed and validated in Belgium. Patients were re-cruited at a tertiary centre in Kraków, Poland.. A total of 479 AF patients completed the JAKQ. Patients on NOACs (n = 276, 57.6%) compared with those on VKAs (n = 175, 36.5%) did not differ regarding demographic and clinical variables. The mean score of the JAKQ was very similar in the NOAC and VKA group (60.7 ± 17.0% vs. 61.6 ± 17.1%; p = 0.4, respectively). The differences in the proportion of correct responses referred to three questions. Consequences of AF, such as blood clots and cerebral infarction, were more obvious for patients on NOACs compared with those on VKAs (81.5% vs. 70.9%; p = 0.01). The patients on NOACs (78.7% vs. 67.6%; p = 0.009) more frequently considered consulting a physician for advice concerning anticoagulant treatment before surgery, while fewer patients on NOACs were aware of the need to take their medication even if they did not feel AF (76.1% vs. 89.7%; p = 0.0004). Only 25.9% of the VKA patients and 49.3% of the NOAC users knew what to do if they missed a dose of the anticoagulant.. The knowledge of arrhythmia and anticoagulation is better regarding the safety issues among subjects on NOACs compared with those on VKAs. Irrespective of the type of oral anticoagulation therapy, education of AF patients should be improved.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Poland; Stroke; Surveys and Questionnaires; Vitamin K

Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH.. We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03).. Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Drug Administration Schedule; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Assessment; Thromboembolism; Treatment Outcome; Vitamin K

Optimal time in therapeutic range (TTR) of vitamin K antagonists (VKAs) is crucial for cardiovascular events (CVEs) prevention in non-valvular atrial fibrillation (NVAF). The relationship between temporal changes of TTR and the incidence of CVEs has been poorly investigated. We investigated 1) temporal trends of TTR in a long-term follow-up of NVAF patients; 2) the incidence of CVEs according to changes of TTR.. Prospective observational study including 1341 NVAF outpatients (mean age 73.5 years, 42.5% male) starting VKAs. Patients were divided into 4 groups: Group 0: Optimal TTR, consistently ≥70% (n = 241); Group 1: Temporally worsening TTR, from above to below 70% (n = 263); Group 2: Temporally improving TTR, from below to above 70% (n = 270); Group 3: Suboptimal TTR, consistently <70% (n = 567).. In a mean follow-up of 37.7 months (4214.2 patient-years), 108 CVEs occurred (2.6%/year). Survival analysis showed a graded increased risk of CVEs in relation to temporal changes in TTR, with the worst outcomes in Groups 1 and 3 (log-rank test p = 0.013). Multivariable Cox proportional hazards regression analysis showed that Group 1 vs. 0 (HR: 2.096; 95%CI 1.061-4.139, p = 0.033), Group 3 vs. 0 (HR: 2.292; 95%CI 1.205-4.361, p = 0.011), CHA. A decrease of TTR <70% over time is observed in almost 20% of NVAF patients. Patients with worsening TTR temporally (ie. from initially above 70% to below 70%) have similar risk of CVEs of patients with consistently suboptimal anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Italy; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

CA of AF without discontinuation of DOACs is not inferior to CA without discontinuation of a VKA, with regard to ischemic or hemorrhagic complications.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiac Tamponade; Catheter Ablation; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Vitamin K

There is a lack of data on anticoagulation requirements during ablation of atrial fibrillation (AF). This study compares different oral anticoagulation (OAC) strategies to evaluate risk of bleeding and thromboembolic complications.. We conducted a single-centre study in patients undergoing left atrial ablation of AF. Three groups were defined: 1) bridging: interrupted vitamin-K-antagonists (VKA), INR ≤2, and bridging with heparin; 2) VKA: uninterrupted VKA and INR of > 2; 3) DOAC: uninterrupted direct oral anticoagulants. Bleeding complications, thromboembolic events and peri-procedural heparin doses were assessed.. In total, 780 patients were documented. At 48 h, major complications were more common in the bridging group compared to uninterrupted VKA and DOAC groups (OR: 3.42, 95% CI: 1.29-9.10 and OR: 3.01, 95% CI: 1.19-7.61), largely driven by differences in major pericardial effusion (OR: 4.86, 95% CI: 1.56-15.99 and OR: 4.466, 95% CI, 1.52-13.67) and major vascular events (OR: 2.92, 95% CI: 0.58-14.67 and OR: 9.72, 95% CI: 1.00-94.43). Uninterrupted VKAs and DOACs resulted in similar odds of major complications (overall OR: 1.14, 95% CI: 0.44-2.92), including cerebrovascular events (OR: 1.21, 95% CI: 0.27-5.45). However, whereas only TIAs were observed in DOAC and bridging groups, strokes also occurred in the VKA group. Rates of minor complications (pericardial effusion, vascular complications, gastrointestinal hemorrhage) and major/minor groin hemorrhage were similar across groups.. Our dataset illustrates that uninterrupted VKA and DOAC have a better risk-benefit profile than VKA bridging. Bridging was associated with a 4.5× increased risk of complications and should be avoided, if possible.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Drug Administration Schedule; Female; Germany; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K

In France, anticoagulants are among the most recommended treatments for serious accidents, particularly among the elderly.. The purpose of this study was to evaluate the impact of practical and validated tools designed to reduce the negative effects of vitamin K antagonist (VKA) treatments by assessing patients before and after the tools were implemented.. An exhaustive before and after multi-centric cohort study was performed in the Agen territory. The follow-up period corresponded to the six-month period post-hospitalization. The principal criterion was the time in the therapeutic range (TTR) at values of 2 to 3 according to the Rosendaal method.. The overall time spent in the follow-up period before and after the implementation of the tools in 65- and 74-year-old patients was 58% and 64%, respectively (P=0.584). After the treatments, the TTR in the 85- to 90-year-old patients was 71.1%. An increase was observed in the number of subjects with a TTR≥70% after the implementation of the tools according to age, particularly in the 85- to 90-year-old patients (8 vs. 41; [P=0.01]). Prescription help software revealed a tendency of improvement in TTR values from 61% to 68% (P=0.472). In addition, longer therapeutic periods corresponded to longer patient lifespans (r=0.86).. This study demonstrates the feasibility and advantages of implementing tools to improve the efficacy of VKA treatment in primary care, particularly for patients from 85 to 90 years old. The results should promote the implementation of this type of treatment method at the national level.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; France; Hospitalization; Humans; Male; Risk Factors; Vitamin K

To investigate the incidence and risk of adverse clinical outcomes in a "real-world" cohort of patients with atrial fibrillation (AF) anticoagulated with vitamin K antagonists (VKAs) from the Murcia AF Project in comparison with the warfarin arm of the randomized clinical trial (RCT) AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation).. We included 1361 patients with AF from the Murcia AF Project (recruitment from May 1, 2007, to December 1, 2007) and 2293 from the AMADEUS trial (started in September 2003 and primary completed in March 2006), all taking VKA treatment. After propensity score matching (PSM), we investigated differences in rates and risks of several events, including major bleeding, ischemic stroke, and all-cause mortality at 365 (interquartile range, 275-428) days of follow-up.. After PSM there were 1324 patients for the comparative analysis, whereby annual event rates for most adverse events were significantly higher in the "real-world" population. Cox regression analyses demonstrated that the risk of primary outcomes was also increased in the "real-world" (vs RCT: hazard ratio [HR], 6.32; 95% CI, 2.84-14.03 for major bleeding; HR, 3.56, 95% CI, 1.22-10.42 for ischemic stroke; HR, 5.13, 95% CI, 3.02-8.69 for all-cause mortality). The risk of all other adverse events was higher in the real-world cohort, except for cardiovascular mortality.. This study comparing the Murcia AF Project and the AMADEUS trial demonstrates that there is a great heterogeneity in both populations, which is translated into a higher risk of several adverse outcomes in the real-world cohort, including major bleeding, ischemic stroke, and mortality.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Hemorrhage; Humans; Male; Observational Studies as Topic; Propensity Score; Randomized Controlled Trials as Topic; Regression Analysis; Stroke; Vitamin K

Despite the increasing utilization of direct oral anticoagulant (DOAC) prescriptions, vitamin K antagonists (VKAs) remain the treatment of choice for treating and preventing thromboembolic events. The morbidity and mortality of VKAs are partly due to the difficulty of keeping the patient within the therapeutic range. For patients treated by VKA, time in therapeutic range (TTR) is a quality parameter of treatment, widely used in clinical trials but rarely by prescribers. It is well established that its use correlates with the risk of hemorrhage, thrombosis or mortality. We studied this parameter in a cohort of patients to evaluate the quality of their therapeutic follow-up and tried to identify risk factors for low TTR.. The study was made in collaboration with LaboSud Oc Biologie for a duration of 4 months. It included 3387 patients representing 2,4029 INR. We calculated the patients' TTR. The laboratory transmitted to us the sex and age of each patient and the VKA molecule used, the therapeutic range and the specialty of the prescriber. We then analyzed the odds ratio associated with these different factors.. The mean TTR was 68%, close to the TTR recommended by scientific societies. Patient's sex was the only statistically correlated factor, with a worse equilibrium in females taking VKAs (OR=1.22, 95% CI: 1.06-1.39, P=0.00552). Many factors usually correlated with poor equilibrium under VKA have not been studied due to lack of information.. Given the context of economic restriction and the TTR of our cohort close to the recommended 70%, there would be no benefit in terms of safety to prefer DOAC for the patients involved in this study. Regular monitoring of the individual patient's as well as the cohort's TTR should optimize the management of patients receiving VKAs.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenindione; Risk Factors; Sex Factors; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

To investigate the incidence of bleeding events in atrial fibrillation (AF) patients treated with vitamin K (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) screened for the presence of liver fibrosis (LF).. Previous studies provided conflicting results on bleeding risk in AF patients with liver disease on VKAs, and no data on NOACs in this setting are available.. Post-hoc analysis of a prospective, observational multicentre study including 2330 AF outpatients treated with VKAs (n = 1297) or NOACs (n = 1033). Liver damage was quantified by the FIB-4 score (>3.25), a validated marker of LF. The primary endpoint was the incidence of any bleeding, according to ISTH classification.. A high FIB-4 was present in 129 (5.5%) patients: 77 (5.9%) on VKA and 52 (5.0%) on NOACs (p = 0.344). During follow-up, 357 (15.3%) patients experienced a bleeding: 261 (80 major and 180 minor) with VKAs (7.2%/year), and 96 (40 major and 56 minor) with NOACs (6.4%/year). In VKA-treated patients, but not in those on NOACs, FIB-4 >3.25 was associated with higher major bleeding (14.3% vs. 5.6%, log-rank test p < 0.001). Multivariable Cox regression model showed that FIB-4 was associated with major bleeding only in VKA-treated patients (HR: 3.075, 95% CI 1.626-5.818, p = 0.001). On multivariable analysis, FIB-4 was not significantly associated with CVEs neither in VKA or NOAC-treated patients.. We found a significant association between LF and major bleedings in AF patients treated with VKA, which was not evident in patients on NOACs.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Incidence; Liver Cirrhosis; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke; Vitamin K

Whether direct oral anticoagulants (DOACs) are safer and more effective than vitamin K antagonist (VKA) for preventing thrombotic events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains unknown.Methods and Results:Between April 2011 and March 2014, data from 2,045 consecutive patients who underwent PCI were retrospectively examined. Of them, 129 patients treated with oral anticoagulants (OACs) and antiplatelet agents because of AF were enrolled. Primary bleeding outcome was a composite of major and minor bleeding, as per the Thrombolysis in Myocardial Infarction criteria. Secondary efficacy outcome was a composite outcome of death, myocardial infarction (MI), stroke, and target-lesion revascularization (TLR). Of the 129 patients, VKA was used in 84 and DOACs in 45. The mean time in the therapeutic range for the VKA group was 52.6%. The ratio of CHA. Compared with DOACs, VKA with poorly controlled INR and antiplatelet agents correlated with adverse outcomes of death, MI, stroke, and TLR in patients undergoing PCI.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Treatment Outcome; Vitamin K

Canadian guidelines recommend non vitamin K antagonists (NOACs) in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF), but NOACs are more expensive than VKAs. Canada has a universal healthcare system that covers the cost of NOACs for select patient groups. Ability to pay for NOACs may influence their use. We reviewed medical charts of Hamilton General Hospital outpatients under the age of 65 with a new diagnosis of AF who were referred for initiation of OAC therapy. We contacted these patients by phone and asked them to complete a questionnaire regarding their OAC choice, economic factors that may have influenced this choice (income, insurance) and the financial burden of OAC therapy. We included 110 patients, mean age 56 years, and 26.4% females. NOAC users had a higher median neighborhood income than VKA users (p = 0.0144, n = 110). 73 patients responded to the questionnaire. NOAC users reported higher annual household income (p = 0.0038, n = 73). Patients with private insurance were more likely to use NOACs than those without insurance (p = 0.0496, n = 73). The cost of NOACs and ability to pay is a determinant of their use Ontario patients under the age of 65. This two tiered provision of care appears to contradict the values of Canada's universal healthcare system.

Topics: Atrial Fibrillation; Cost of Illness; Female; Fibrinolytic Agents; Health Expenditures; Humans; Income; Insurance, Health; Male; Middle Aged; Ontario; Stroke; Surveys and Questionnaires; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Electric Countershock; Heparin; Humans; Intention; Pyrazoles; Pyridones; Vitamin K

Achieving a good satisfaction with anticoagulant treatment should be a target in Atrial Fibrillation (AF) patients.. To ascertain the perception of patients regarding burdens and benefits of anticoagulation with Vitamin K Antagonists (VKA).. This was a multicenter cross-sectional/retrospective study conducted throughout Spain, in which AF patients taking VKA during the last year, attended at primary care setting were included. The Anti-Clot-Treatment Scale (ACTS) was used to determine perceived burdens and benefits with anticoagulation.. Overall, 1,386 patients (mean age 77.4 ± 8.7 years; 48.6% women; 64.2% permanent AF; CHA2DS2-VASc 3.9 ± 1.5; HAS-BLED 1.6 ± 0.9) were analyzed. The adequate anticoagulation control was achieved by 56.9/60.6% of patients according to direct method/Rosendaal method, respectively. Overall, mean ACTS Burdens scale score was 49.4 ± 8.8 and mean ACTS Benefits scale score 11.2 ± 2.2. Active patients, polymedication, elderly and visits to the nurse were associated with higher scores in the ACTS Burdens scale (lower perceived burden), whereas visits to the emergency department and primary care physician were associated with lower scores in the ACTS Burdens scale (higher perceived burden). Active patients, number of INR determinations, visits to the nurse, and an adequate INR control were associated with higher scores in the ACTS Benefits scale (higher perceived benefit), whereas visits to the emergency department and to the primary care physician were associated with lower scores in the ACTS Benefits scale (lower perceived benefit).. Satisfaction with treatment was high among patients with AF chronically anticoagulated with VKA, suggesting that quality of life is not impaired in this population.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; Male; Patient Satisfaction; Quality of Life; Retrospective Studies; Spain; Vitamin K

Oral vitamin K antagonists (VKAs) are commonly used in older adults. To ensure the efficiency and safety of these drugs, the international normalized ratio (INR) must be monitored. The time in therapeutic range (TTR) is an internationally recommended assessment of the anticoagulation quality.. Our study aimed to assess the TTR of VKAs in a hospitalized geriatric population and identify factors associated with low TTR.. This was a multicenter retrospective study of data from 1899 patients with a mean age of 87 years between 2013 and 2015 in the geriatric units of four French hospitals. The data collection consisted of 2450 VKA prescriptions. We excluded prescriptions with a duration of < 7 days, monitoring with fewer than two INR values and patients with prosthetic heart valves. TTR was assessed using the Rosendaal method. Factors associated with a low TTR (< 50%) were assessed using a non-parametric method.. The mean TTR observed in this population was 42.6%. The TTR was < 50% for 62.5% of the patients included in this study. Significant associations were found between TTR < 50% and aspartate transaminase (AST), alkaline phosphatase (ALT), thyroid-stimulating hormone (TSH), prescription duration, fluconazole instauration, hemoglobin, and C-reactive protein (CRP).. Both our results and those in the literature indicate that TTR in geriatric populations is lower than that in the general population. Most patients had an insufficient TTR, exposing them to an increased risk of thromboembolic and hemorrhagic events. These data provide a perspective on poor-quality anticoagulation and illustrates the difficulty of using VKAs in geriatric patients.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Anticoagulants; Aspartate Aminotransferases; Atrial Fibrillation; Blood Coagulation; C-Reactive Protein; Female; Fibrinolytic Agents; Hemoglobins; Hemorrhage; Hospitalization; Humans; International Normalized Ratio; Male; Retrospective Studies; Thromboembolism; Thyrotropin; Vitamin K

The safety of direct oral anticoagulants (DOACs) in oldest old patients with nonvalvular atrial fibrillation (NVAF) in daily clinical practice has not been systematically assessed. This study examined the safety of DOACs and dicumarol (a vitamin K antagonist) in NVAF geriatric patients.. Prospective study from January 2010 through June 2015, with follow-up through January 2016.. Geriatric medicine department at a tertiary hospital.. A total of 554 outpatients, 75 years or older, diagnosed of NVAF and starting oral anticoagulation.. The main outcome was bleeding, which was classified into major (including those life-threatening) and nonmajor episodes. Statistical analyses were performed with Cox regression.. A total of 351 patients received DOACs and 193 dicumarol. Patients on DOACs were older, with more frequent comorbidities, mobility limitation and disability in activities of daily living, as well as higher mortality, than those treated with dicumarol. The incidence of any bleeding was 19.2/100 person-years among patients on DOACs and 13.7/100 person-years on dicumarol; corresponding figures for major bleeding were 5.2 for those on DOACs, and 3.3 for those on dicumarol. In crude analyses, hazard ratios (95% confidence intervals) for any bleeding, and for mayor bleeding in patients on DOACs vs dicumarol were 1.60 (1.04-2.44) and 2.22 (0.88-5.59), respectively. Excess risk of bleeding associated with DOACs vs dicumarol disappeared after adjustment for clinical characteristics, so that corresponding figures were 1.19 (0.68-2.08) and 1.01 (0.35-2.93). Results did not vary across subgroups of high-risk patients.. In very old patients with NVAF, the higher risk of bleeding associated with DOACs vs dicumarol could be mostly explained by the worse clinical profile of patients receiving DOACs. Risk of bleeding was rather high, and warrants close clinical monitoring.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Comorbidity; Dabigatran; Dementia; Dicumarol; Disabled Persons; Follow-Up Studies; Hemorrhage; Humans; Mobility Limitation; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Vitamin K

The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce.. Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out.. Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34).. With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Female; Follow-Up Studies; Germany; Hemorrhage; Humans; Male; Middle Aged; Phenprocoumon; Stroke; Vitamin K; Young Adult

Non-vitamin K antagonist oral anticoagulants (NOACs) require renal dose adjustment. The most common estimates of renal function in clinical practice are derived from estimated glomerular filtration rate (eGFR; Modified Diet in Renal Disease [MDRD] or the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). However, the landmark stroke prevention trials and product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for drug eligibility and dose adjustment. We sought to evaluate the agreement in NOAC dosing between these 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease.. We identified 831 patients with non-dialysis-dependent chronic kidney disease and atrial fibrillation (CHA. The use of eGFR resulted in significant misclassification with respect to NOAC dosing. Compared with eCrCl, the MDRD eGFR and CKD-EPI eGFR misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in undertreatment (eg, inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent overtreatment (eg, inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI).. MDRD and CKD-EPI eGFR fail to correctly identify a significant proportion of patients who require NOAC dose adjustment, limiting their clinical utility. Cockcroft-Gault eCrCl should be calculated for all patients in whom a NOAC is being prescribed.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Renal Insufficiency, Chronic; Retrospective Studies; Severity of Illness Index; Thromboembolism; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Emergency Medicine; Humans; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Emergency Medicine; Humans; Stroke; Vitamin K

Intracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH.. Search for individual risk factors and bleeding risk scores (HAS-BLED, ATRIA and ORBIT) associated with ICHs in patients with atrial fibrillation treated with VKAs.. This is a retrospective case-control study in a single Thrombosis Center. During a 7-year period, patients with nonvalvular atrial fibrillation (NVAF) who developed ICH during VKAs were identified as cases. Four control patients matched for gender, age and length of VKAs were assigned to each case. The association between considered risk factors and ICHs was evaluated using a linear logistic regression method and expressed as odds ratio. Receiver operator characteristic (ROC) curves to assess the predictive ability of bleeding risk scores HAS-BLED, ATRIA and ORBIT were also evaluated.. Fifty-one cases of ICH, most of whom were 80 years of age or older (72.5%), were retrieved from the Thrombosis Center's database. Compared to 204 controls, no individual risk factors were associated with ICH. Poor ability to predict ICH was also found using ROC curves (C-statistic for HAS-BLED, ATRIA, and ORBIT were 0.55, 0.53 and 0.54, respectively).. ICHs during VKA therapy preferentially occur in very elderly patients. The risk of ICH is not predicted by the commonly used risk scores.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Intracranial Hemorrhages; Italy; Male; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin K

The TIMI-AF score predicts poor outcomes in patients with atrial fibrillation (AF) and guides selection of anticoagulant therapy by identifying clinical benefit of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA).. Our objective was to determine the ability to predict cardiovascular events according to the TIMI-AF score in a real-world population.. Retrospective observational study of VKA-naïve patients with AF was seen at a cardiology outpatient clinic in Spain between November 2012 and August 2014. We recorded adverse events (myocardial infarction, systemic embolism or stroke, major bleeding, and death).. The study population comprised of 426 patients (50.7% men, mean age, 69 ± 14 years). The TIMI-AF score identified 372 patients (87.3%) with a low risk, 50 patients (11.7%) with an intermediate risk, and 4 patients (0.9%) with a high risk. After a mean follow-up of 423.4 ± 200.1 days, 37 patients (9%) experienced an adverse event. Patients with a TIMI-AF score ≥ 7 had a poorer cardiovascular prognosis (HR, 6.1; 95%CI, 3.2-11.7; P < 0.001). The area under the ROC curve of TIMI-AF was 0.755 (95%CI, 0.669-0.840; P < 0.001), which was greater than that of CHA. The TIMI-AF risk score can identify patients who are at greater risk of cardiovascular events and a poor net clinical outcome with a better diagnostic yield than CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Outpatients; Retrospective Studies; Risk Assessment; Spain; Survival Rate; Thromboembolism; Thrombolytic Therapy; Vitamin K

The safety and efficacy of a minimally interrupted novel oral anticoagulant (NOAC) strategy at the time of atrial fibrillation (AF) ablation is uncertain. The purpose of this study was to compare rates of bleeding and thromboembolic events between minimally interrupted NOAC and uninterrupted vitamin K antagonist (VKA) in patients undergoing AF ablation.. This was a retrospective single-center cohort study of consecutive patients who underwent AF catheter ablation between January 2013 and April 2017. Endpoints included major bleeding, clinically relevant non-major bleeding and systemic thromboembolic event from the time of ablation through 30 days. Bleeding events were defined by the Bleeding Academic Research Consortium (BARC) and International Society on Thrombosis and Haemostasis (ISTH).. A total of 637 patients were included in the analysis, 520 patients used uninterrupted VKA and 117 patients minimally interrupted NOAC (dabigatran: n = 68; apixaban: n = 30; rivaroxaban, n = 14; edoxaban, n = 5). The rate of clinically relevant non-major bleeding was lower in the NOAC group in comparison to the VKA group (BARC type 2: 2.6% versus 8.3%, P = 0.03; ISTH: 0% versus 3.8%, P = 0.03). Rates of major bleeding were similar between groups (BARC type 3 to 5: 3.4% versus 4.2%, P = NS; ISTH: 6.0% versus 8.7%, P = NS; for NOAC and VKA groups, respectively). Rates of systemic embolism were 0% with minimally interrupted NOAC, and 0.6% with uninterrupted VKA (P = NS).. In patients undergoing AF ablation, anticoagulation with minimally interrupted NOAC was associated with fewer clinically relevant non-major bleeding events in comparison with uninterrupted VKA without compromising thromboembolic safety.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Cohort Studies; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Netherlands; Outcome and Process Assessment, Health Care; Postoperative Complications; Retrospective Studies; Thromboembolism; Vitamin K

This study aimed to evaluate the risk of major bleeding among two cohorts of nonvalvular atrial fibrillation patients newly initiating a vitamin K antagonist (VKA) or apixaban in a real-world setting in Italy.. A retrospective study using a large administrative database of Italian local health units was performed, using data from ten local health units and patients were included from the date of new initiation of apixaban or VKAs from January 2012 to June 2015.. Risk of major bleeding was calculated using an adjusted Cox regression model. Compared with VKA, apixaban had a significantly lower risk of major bleeding (hazard ratio = 0.44 [95% CI: 0.12-0.97]).. In this analysis, apixaban was associated with a lower risk of major bleeding compared with VKA.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Evidence-Based Medicine; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Risk; Vitamin K

The association between use of non-vitamin K antagonist oral anticoagulants (NOACs) with cognitive impairment in atrial fibrillation (AF) remains unknown.. An electronic search of Medline, Embase, Cochrane Library databases and ClinicalTrials.gov Website will be performed for randomized controlled trials (RCTs) that reported cognitive impairment events and observational nationwide database studies that reported adjusted hazard ratio (HR) in AF patients with NOACs. The primacy outcome will be a composite of any forms of cognitive impairment. HRs and their 95% confidence intervals (95% CI) will be calculated by using fixed- and random-effects models. Subgroup analyses will be undertaken based on individual NOACs, study types and follow-up duration.. This study will provide evidence of the association between use of NOACs and risk of cognitive impairment in patients with AF by pooling the results of RCTs and real-world studies.. The results will bring about vigorous evidence in this topic and provide optimal anticoagulation strategy in AF patients at high risk of cognitive disorder.. Ethical approval is not applicable for this study.. CRD42018103849.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cognitive Dysfunction; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Systematic Reviews as Topic; Vitamin K

Atrial fibrillation (AF) patients on a vitamin K antagonist (VKA) with time in therapeutic range (TTR) ≥70% are not recommended to switch to a direct oral anticoagulant according to guidelines.. This study sought to assess future TTR and risk of stroke/thromboembolism and major bleeding among AF patients on VKA with TTR ≥70%.. The authors used Danish nationwide registries to identify AF patients on VKA from 1997 to 2011 with available international normalized ratio values. Patients were included 6 months after VKA initiation, divided according to TTR, and followed for 12 months after inclusion. Cox proportional hazard models estimated hazard ratios (HRs). TTR was examined both as a baseline variable and as a time-dependent covariate in the Cox models.. Of the 4,772 included AF patients still on VKA 6 months after initiation, 1,691 (35.4%) had a TTR ≥70%, and 3,081 (65.6%) had a TTR <70%. Among patients with prior TTR ≥70% still on treatment 12 months after inclusion, only 513 (55.7%) still had a TTR ≥70%. Compared with prior TTR ≥70%, prior TTR <70% was not associated with a higher risk of stroke/thromboembolism (HR: 1.14; 95% confidence interval [CI]: 0.77 to 1.70) or major bleeding (HR: 1.12; 95% CI: 0.84 to 1.49). When the authors estimated TTR time-dependently during follow-up, TTR <70% was associated with an increased risk of stroke/thromboembolism (HR: 1.91; 95% CI: 1.30 to 2.82) and major bleeding (HR: 1.34; 95% CI: 1.02 to 1.76).. Among AF patients on VKA, almost one-half of patients with prior TTR ≥70% had TTR <70% during the following year. Prior TTR ≥70% per se had limited long-term prognostic value.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Denmark; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Proportional Hazards Models; Registries; Stroke; Thromboembolism; Vitamin K

This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF).. We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin. We developed novel methods to calculate the number and proportion of days with potential DDIs with NOAC/warfarin. Multivariate logistic regressions were utilized to evaluate the associations between switching to NOACs, exposure to potential DDIs, and major bleeding events.. Among a total of 4126 patients with AF, we found a significantly lower number of potential DDIs and the average proportion of days with potential DDIs in switchers than non-switchers. The number of potential DDIs (AOR 1.14, 95% CI 1.02-1.27) and the HAS-BLED score (AOR 1.64, 95% CI 1.48-1.82) were significantly and positively associated with the likelihood of a major bleeding event. The proportion of days with potential DDIs was also significantly and positively associated with risk for bleeding (AOR 1.42, 95% CI 1.03, 1.96). We did not find significant associations between switching to NOACs and major bleeding events.. The number and duration of potential DDIs and patients' comorbidity burden are important factors to consider in the management of bleeding risk in working-age AF adults who take oral anticoagulants.

Topics: Administration, Oral; Adolescent; Adult; Anticoagulants; Atrial Fibrillation; Databases, Factual; Drug Interactions; Drug Substitution; Female; Hemorrhage; Humans; Male; Middle Aged; Polypharmacy; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; Vitamin K; Warfarin; Young Adult

Background and Purpose- Acute ischemic strokes under vitamin K antagonist (VKA) treatment are not uncommon, but intravenous thrombolysis (IVT) is not recommended for international normalized ratio (INR) >1.7 because of the excess bleeding risk. However, VKA-induced anticoagulation can be easily reversed by IV infusions of 4-factor prothrombin complex concentrate bolus and vitamin K. Our pilot study aimed to determine whether IVT immediately after anticoagulation reversal could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Methods- Consecutive acute ischemic stroke patients, otherwise eligible for IVT except for VKA intake and INR >1.7, were given IVT after infusing 4-factor prothrombin complex concentrate and vitamin K. Safety and efficacy were assessed clinically and by cerebral imaging at 24 hours. Results- Twenty-six patients (age, 77.8±12.8 years; atrial fibrillation, 84.6%; initial National Institutes of Health Stroke Scale, 11.6±5.6) were prospectively included. INR values were 2.3±0.6 initially and 1.3±0.2, 5 minutes postreversal. No symptomatic intracranial hemorrhage or thrombotic events occurred during the first 3 days. One patient developed major systemic hemorrhoidal bleeding that required blood transfusion; 61.5% of the patients were independent (modified Rankin Scale score of ≤2) at 3 months. Conclusions- A reversal strategy of 4-factor prothrombin complex concentrate bolus and vitamin K before IVT could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Well-designed, randomized controlled trials are warranted to confirm these preliminary findings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Pilot Projects; Stroke; Thrombolytic Therapy; Vitamin K

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26-1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27-1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17-1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Hemorrhage; Humans; Inpatients; Male; Middle Aged; Outpatients; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Vitamin K; Warfarin

This study aimed to describe patterns of long-term antithrombotic use in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) in Korea and their impacts on clinical events before introduction of non-vitamin K antagonist oral anticoagulants (NOAC) into practice in 2015.. Patients with NVAF who were admitted due to the AIS and discharged no later than 2008 were enrolled retrospectively. Data were collected at 11 time points during the first 3 years of follow-up. The primary outcome event was a composite of stroke recurrence, major bleeding, and death. Vitamin K antagonist (VKA) users were categorized into a well-controlled INR group and a poorly-controlled INR group (modified TTR ≥47.0% vs <47.0%).. Of 1,350 patients enrolled in this study, 95% were on antithrombotic medications at discharge. The rate of VKA usage decreased over time (77% and 40% at discharge and 3 years, respectively). The cumulative event rates of the primary outcome differed by treatment patterns. Among the 10 most frequent treatment types, the highest outcome rate was observed in patients who started with VKA-only therapy but discontinued VKAs during follow-up without restarting (70.2%); this was followed by those starting with antiplatelet-only therapy and stopping it without restart (66.7%). Among VKA users, the 3-year cumulative primary outcome rates were higher in the poorly-controlled INR group than the well-controlled INR group (24.5% vs 15.7%; p = 0.015).. Our study revealed that, in pre-NOAC era, there was a wide spectrum of long-term antithrombotic use. The incidence of the composite outcome also varied by patterns of antithrombotic use.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Republic of Korea; Retrospective Studies; Stroke; Thrombosis; Treatment Outcome; Vitamin K

Anticoagulation with vitamin K antagonists continues to be a challenging task given the difficulty of achieving a correct time in therapeutic range (TTR). The SAMeTT. We prospectively included 212 consecutive patients with nonvalvular atrial fibrillation under treatment with acenocoumarol for at least 6 months that were attended in a cardiology outpatient clinic and were categorized as adherent to medication. We carried out a multivariate regression analysis to detect the independent predictive factors of good control. In all patients. A total of 128 (60.4%) patients presented TTR <70% (average TTR = 63.2). We identified body mass index (OR 0.94, 95%CI 0.89-0.99, p=0.032) and regular vitamin K intake (OR 0.53, 95%CI 0.28-0.99, p= 0.046) as independent predictors of poor anticoagulation control. The discriminatory power of a clinical-genetic model derived from our cohort was significantly better compared to the SAMeTT. In our study the SAMeTT

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Body Mass Index; Female; Humans; Male; Models, Genetic; Multivariate Analysis; Prospective Studies; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Heart Valve Prosthesis; Humans; Stroke; Thromboembolism; Vitamin K; Warfarin

Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction.. We conducted a multicenter, prospective, non-interventional study. Patients with CHADS. A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS. INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Male; Middle Aged; Personal Satisfaction; Prospective Studies; Republic of Korea; Surveys and Questionnaires; Vitamin K

Until recently, vitamin K antagonists (VKAs) were the only form of anticoagulation for the prevention of thromboembolic complications in patients with atrial fibrillation or venous thromboembolisms. Various caregivers are involved in anticoagulation care. Criticism of the support by the thrombosis department focused mainly on the lack of guarantees regarding the interinstitutional anticoagulation chain of care. Initiatives have now been deployed to improve this support, as described in the national integrated anticoagulation care standard (LSKA, Landelijke Standaard Ketenzorg Antistolling) and the national primary care anticoagulation agreement (LESA, Landelijke Eerstelijns Samenwerkingsafspraken). However, rapidly increasing use of direct oral anticoagulants (DOACs) has dramatically altered anticoagulation care. Patients and caregivers are more often confronted with uncertainty about treatment coordination. This article aims to sketch frameworks for responsible anticoagulation care. We examine different topics, such as coordination, organisation of follow-up, availability for answering questions and switching from VKA to DOAC.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

Direct-acting oral anticoagulants (DOACs) have become available for the prevention of stroke in patients with atrial fibrillation (AF). Conflicting results have been published on the risk of acute myocardial infarction (AMI) with the use of DOACs in comparison with vitamin K antagonists (VKAs). The objective of the present study was to evaluate the risk of AMI in patients with AF who are exposed to either VKAs, DOACs or low-dose (< 325 mg) aspirin.. We conducted a population-based cohort study using data from the Clinical Practice Research Datalink (2008-2014). The study population (n = 30 146) consisted of all patients ≥18 years with a diagnosis of AF who were new users of VKAs, DOACs (rivaroxaban and dabigatran) or aspirin. Cox proportional hazards models were used to estimate the hazard ratio (HR) of AMI for users of DOACs or aspirin vs. VKA. Adjustments were made for age, gender, lifestyle, risk factors, comorbidity and other drugs.. The risk of AMI was doubled when we compared current use of DOACs with current use of VKAs [adjusted HR 2.11; 95% confidence interval (CI) 1.08, 4.12] and for current users of aspirin vs. current VKA users (adjusted HR 1.91; 95% CI 1.45, 2.51).. There is a twofold increase in the risk of AMI for users of DOACs, in comparison with VKAs, in AF therapy. In addition, the results suggested that in patients with AF, the incidence of AMI is higher during aspirin monotherapy than during the use of VKAs.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Dabigatran; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Vitamin K

To compare the satisfaction of patients treated with vitamin K antagonists (VKA) with that of patients treated with direct oral anticoagulants (DOACs) and to determine the impact on quality of life of both treatments in patients with nonvalvular atrial fibrillation (NVAF).. Cross-sectional multicenter study in which outpatients with NVAF completed the ACTS (Anti-Clot Treatment Scale), SAT-Q (Satisfaction Questionnaire) and EQ-5D-3L (EuroQol 5 dimensions questionnaire, 3 level version) questionnaires.. The study population comprised 1337 patients, of whom 587 were taking DOACs and 750 VKAs. Compared with VKAs, DOACs were more commonly prescribed in patients with a history of stroke and in patients with a higher thromboembolic risk. The study scores were as follows: SAT-Q: 63.8 ± 17.8; EQ-5D-3L total score: 75.6 ± 20.9; visual analog scale: 63.1 ± 20.6; ACTS Burdens: 51.8 ± 8.4 and ACTS Benefits: 11.9 ± 2.4. The ACTS Burdens score and ACTS Benefits score were higher with DOACs than with VKAs (54.83 ± 6.11 vs 49.50 ± 9.15; p < 0.001 and 12.36 ± 2.34 vs 11.48 ± 2.46; p < 0.001 respectively).. NVAF patients treated with oral anticoagulants had many comorbidities and a high thromboembolic risk. Satisfaction and quality of life with oral anticoagulants were high, although they were both better with DOACs than with VKAs.

Topics: Anticoagulants; Atrial Fibrillation; Comparative Effectiveness Research; Cost of Illness; Cross-Sectional Studies; Humans; Personal Satisfaction; Quality of Life; Risk; Stroke; Surveys and Questionnaires; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Vitamin K; Warfarin

Warfarin acts by inhibiting the reduction of vitamin K (VK) to its active form, thereby decreasing the production of VK-dependent coagulation proteins. The aim of this research is to develop a joint model for the VK-dependent clotting factors II, VII, IX and X, and the anticoagulation proteins, proteins C and S, during warfarin initiation.. Data from 18 patients with atrial fibrillation who had warfarin therapy initiated were available for analysis. Nine blood samples were collected from each subject at baseline, and at 1-5, 8, 15 and 29 days after warfarin initiation and assayed for factors II, VII, IX and X, and proteins C and S. Warfarin concentration-time data were not available. The coagulation proteins data were modelled in a stepwise manner using NONMEM. One patient was administered VK and was excluded from the analysis. Each kinetic-pharmacodynamic model consisted of two parts: (1) a common one-compartment pharmacokinetic model with first-order absorption and elimination for warfarin; and (2) an inhibitory E. The joint model represents the first work to quantify the influence of warfarin on all six VK-dependent coagulation proteins simultaneously. Future work will expand the model to predict the influence of exogenously administered VK on the time course of clotting factor concentrations after warfarin overdose and during perioperative warfarin reversal procedures.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Factors; Blood Proteins; Female; Half-Life; Humans; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Vitamin K; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Component Transfusion; Breast Neoplasms; Female; Heart Failure; Humans; International Normalized Ratio; Plasma; Pleural Effusion, Malignant; Preoperative Care; Stroke; Thoracentesis; Transfusion Reaction; Vitamin K; Warfarin

The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs).. Using Danish nationwide registry data, we identified AF patients initiating either a VKA or a NOAC from 22 August 2011 until 30 September 2016. We compared patient characteristics including age, gender, comorbidities, concomitant pharmacotherapy and CHA. The study population comprised 51 981 AF patients of whom 19 989 (38.5%) were initiated on a VKA, 13 242 (25.5%) on dabigatran, 8475 (16.3%) on rivaroxaban and 10 275 (19.8%) on apixaban. Those patients initiated on apixaban had higher mean ± SD CHA. Atrial fibrillation patients who were initiated on apixaban had higher stroke risk scores than patients initiated on VKAs. Interestingly, opposite results were found for dabigatran.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Vitamin K; Warfarin

Vitamin K antagonist (VKA) treatment requires routine monitoring using the international normalized ratio (INR). However, different INR assays may vary in their results. The aim of this study was to assess the agreement of three different INR methods, compared with thrombin generation, in patients on VKA treatment.. Sixty patients attending the Anticoagulation Clinic at Mater Dei Hospital (Msida, Malta) for VKA monitoring between August and September 2015 were enrolled. The INR was tested using a point-of-care (POC) device (CoaguChek XS Plus, Roche Diagnostics) for both capillary and venous blood samples, a photo-optical (Sysmex CS-2100i/CA-1500, Siemens) and a mechanical clot detection system (Thrombolyzer XRC, Behnk Elektronik). All assays used human recombinant thromboplastin as reagent. Thrombin generation was performed using the calibrated automated thrombogram.. There was a negative curvilinear correlation between the endogenous thrombin potential and different INR assays (r≤-.75) and a strong positive linear correlation between the CoaguChek XS Plus on capillary samples and the other INR methodologies (r≥.96).. All different INR assays showed good correlation with the thrombin generation potential. The POC INR showed one of the highest correlation coefficients with thrombin generation, confirming the POC devices as an accurate, valid alternative to laboratory INR in VKA patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Female; Humans; International Normalized Ratio; Male; Middle Aged; Point-of-Care Systems; Reproducibility of Results; Thrombin; Venous Thromboembolism; Vitamin K; Warfarin

Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world. An appropriate management of treated patients is crucial for their efficacy and safety. The prospective, observational, multicenter, inception-cohort FCSA-START Register, a branch of START Register (NCT02219984) included VKA-treated patients managed by centers of Italian Federation of anticoagulation clinics (AC). Baseline patient characteristics and data during treatment were analyzed and compared with those of ISCOAT study, performed by the Federation and published in 1996/7. 5707 naïve patients [53% males, mean age 73.0 years (28.1% >80 years)], 61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism were included. During the 8906 patient-years (pt-yrs) of observation, 123 patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non-major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more frequent in elderly (≥70 years; p = 0.04), and during initial 3-month therapy (p = 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results <3.0, increasing to 12.5% for INR ≥ 4.5. Thrombotic events were 47 (0.53% pt-yrs; 4 fatal 0.04% pt-yrs). Compared with ISCOAT-1996/7 results, patients older than 80 y are increased from 8 to 28% (p < 0.01), and those treated for AF are increased from 17 to 61%. The quality of anticoagulation control and incidence of MB are not different. However, thrombotic complications fell drastically from 3.5 to 0.53% pt-yrs (p < 0.01), with lower mortality (p = 0.01). VKA-treated patients monitored in Italian AC have good clinical results, with low bleeding and thrombotic complications rates. Important changes in the treated population and improvement in thrombotic complications are detected compared with the ISCOAT-1996/7 study.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Female; Heart Valve Prosthesis; Hemorrhage; History, 20th Century; History, 21st Century; Humans; Incidence; Italy; Male; Middle Aged; Population Groups; Registries; Risk Factors; Thromboembolism; Vitamin K; Warfarin

Data evaluating the impact of the periprocedural administration of novel oral anticoagulants (NOACs) on complications in the setting of pulmonary vein (PV) isolation using cryoballoon (CB) is limited. In the present study, our aim was to analyze procedural characteristics and incidence of complications in those patients who underwent CB ablation for atrial fibrillation and the impact of NOACs on adverse events compared with vitamin K antagonists (VKAs). Consecutive patients with drug resistant atrial fibrillation who underwent PV isolation by CB as index procedure were retrospectively included in our analysis. In group I, 290 of 454 patients (63.9%) received VKAs (warfarin: n = 222 and acenocoumarol: n = 68), and in group II, 164 of 454 patients (36.1%) were treated with NOACs (rivaroxaban: n = 71; dabigatran: n = 60; and apixaban: n = 33). Age was significantly higher in the group II (62.8 ± 9.7 vs 58.6 ± 11.3; p <0.001). During the study period, 454 consecutive patients (male 71%, age 60.1 ± 10.9 years) were enrolled. Major complications occurred in 9 patients (2.0%): peripheral vascular complications were observed in 6 patients (1.3% per procedure), persistent phrenic nerve palsy occurred in 2 (0.4%), and transient ischemic attacks in 1 (0.2%). In both groups, the incidence of major complications was similar (group I [VKAs]: 7 patients [2.4%] vs group II [NOACs]: 2 patients [1.2%]; p = 0.5). In conclusion, CB ablation is a safe procedure for PV isolation and is associated with low complication rates. The incidence of adverse events in PV isolation using the second-generation CB with the periprocedural administration of NOACs is not significantly different than VKA treatment.

Topics: Ablation Techniques; Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Belgium; Cryosurgery; Dabigatran; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Intraoperative Period; Italy; Male; Middle Aged; Postoperative Complications; Prognosis; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Survival Rate; Thiazoles; Time Factors; Vitamin K

The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events.. To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs.. Retrospective cohort study including patients with nonvalvular AF attending an outpatient anticoagulation clinic of a tertiary hospital. Visits to the outpatient clinic and emergency, as well as hospital admissions to the institution, during 2014 were evaluated. The TTR was calculated through the Rosendaal´s method.. We analyzed 263 patients (median TTR, 62.5%). The low-risk group (score 0-1) had a better median TTR as compared with the high-risk group (score ≥ 2): 69.2% vs. 56.3%, p = 0.002. Similarly, the percentage of patients with TTR ≥ 60%, 65% or 70% was higher in the low-risk group (p < 0.001, p = 0.001 and p = 0.003, respectively). The high-risk group had a higher percentage of adverse events (11.2% vs. 7.2%), although not significant (p = 0.369).. The SAMe-TT2R2 score proved to be effective to predict patients with a better TTR, but was not associated with adverse events.. O escore SAMe-TT2R2 foi desenvolvido visando predizer quais pacientes em anticoagulação oral com antagonistas da vitamina K (AVKs) atingirão um tempo na faixa terapêutica (TFT) adequado (> 65%-70%) no seguimento. Estudos também o relacionaram com a ocorrência de eventos adversos.. Descrever o TFT de acordo com o escore, além de relacionar a pontuação obtida com a ocorrência de eventos adversos adversos em pacientes com fibrilação atrial (FA) não valvar em anticoagulação oral com AVKs.. Estudo de coorte retrospectivo incluindo pacientes com FA não valvar em acompanhamento em ambulatório de anticoagulação de um hospital terciário. Foi realizada uma avaliação retrospectiva de consultas ambulatoriais, visitas a emergência e internações hospitalares na instituição no período de janeiro-dezembro/2014. O TFT foi calculado aplicando-se o método de Rosendaal.. Foram analisados 263 pacientes com TFT mediano de 62,5%. O grupo de baixo risco (0-1 ponto) obteve um TFT mediano maior em comparação com o grupo de alto risco (≥ 2 pontos): 69,2% vs. 56,3%, p = 0,002. Da mesma forma, o percentual de pacientes com TFT ≥ 60%, 65% ou 70% foi superior nos pacientes de baixo risco (p < 0,001, p = 0,001 e p = 0,003, respectivamente). Os pacientes de alto risco tiveram um percentual maior de eventos adversos (11,2% vs. 7,2%), embora não significativo (p = 0,369).. O escore SAMe-TT2R2 foi uma ferramenta eficaz na predição do TFT em pacientes com FA em uso de AVKs para anticoagulação, porém não se associou à ocorrência de eventos adversos.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Decision Support Techniques; Disease-Free Survival; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Predictive Value of Tests; Prothrombin Time; Retrospective Studies; Severity of Illness Index; Stroke; Thromboembolism; Vitamin K; Warfarin

Coexisting cancer in patients with atrial fibrillation (AF) has been associated with thromboembolism and bleeding. We used Danish population-based medical databases to conduct a population-based cohort study that included all AF patients who redeemed a prescription for vitamin K antagonists (VKA) or non-VKA oral anticoagulant (NOAC) between July 2004 and December 2013. We characterized these patients according to the presence (N = 11,855) or absence (N = 56,264) of a cancer diagnosis before redemption of their oral anticoagulant prescription, and then examined their 1-year risk of thromboembolic or bleeding complications or death. We next used Cox regression to compare the hazard ratios for complications among VKA- or NOAC-treated AF patients with versus without a cancer diagnosis, after adjusting for sex, age, and CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Denmark; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Thromboembolism; Vitamin K

Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut-derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med-diet).. This was a prospective single-center study including 912 AF patients treated with vitamin K antagonists (3716 patient-years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med-diet (n=704), and urinary excretion of 11-dehydro-thromboxane B. In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med-diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bacteria; Biomarkers; Cerebrovascular Disorders; Diet, Mediterranean; Female; Gastrointestinal Microbiome; Humans; Intestines; Kaplan-Meier Estimate; Lipopolysaccharides; Male; Myocardial Ischemia; Patient Compliance; Platelet Activation; Prospective Studies; Protective Factors; Risk Factors; Rome; Time Factors; Treatment Outcome; Vitamin K

Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention.. The goal of this study was to investigate NOAC dosing patterns and associated outcomes, i.e., stroke (ischemic stroke and systemic embolism) and major bleeding in patients treated in routine clinical practice.. Using a large U.S. administrative database, 14,865 patients with AF were identified who initiated apixaban, dabigatran, or rivaroxaban between October 1, 2010, and September 30, 2015. We examined use of a standard dose in patients with a renal indication for dose reduction (potential overdosing) and use of a reduced dose when the renal indication is not present (potential underdosing). Cox proportional hazards regression was performed in propensity score-matched cohorts to investigate the outcomes.. Among the 1,473 patients with a renal indication for dose reduction, 43.0% were potentially overdosed, which was associated with a higher risk of major bleeding (hazard ratio: 2.19; 95% confidence interval: 1.07 to 4.46) but no statistically significant difference in stroke (3 NOACs pooled). Among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed. This underdosing was associated with a higher risk of stroke (hazard ratio: 4.87; 95% confidence interval: 1.30 to 18.26) but no statistically significant difference in major bleeding in apixaban-treated patients. There were no statistically significant relationships in dabigatran- or rivaroxaban-treated patients without a renal indication.. In routine clinical practice, prescribed NOAC doses are often inconsistent with drug labeling. These prescribing patterns may be associated with worse safety with no benefit in effectiveness in patients with severe kidney disease and worse effectiveness with no benefit in safety in apixaban-treated patients with normal or mildly impaired renal function.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Pyrazoles; Pyridones; Renal Insufficiency; Retrospective Studies; Rivaroxaban; Stroke; Time Factors; Treatment Outcome; United States; Vitamin K; Young Adult

The need for transesophageal echocardiography (TEE) before catheter ablation of atrial fibrillation (CA-AF) is still being questioned. The aim of this study is to analyze patients' (patients) risk factors of left atrial appendage thrombus (LAAT) prior to CA-AF in daily clinical practice, according to oral anticoagulation (OAC) strategies recommended by current guidelines.. All patients scheduled for CA-AF from 01/2015 to 12/2016 in our center were included and either treated with NOACs (novel-OAC; paused 24-hours preablation) or continuous vitamin K antagonists (INR 2.0-3.0). All patients received a preprocedural TEE at the day of ablation. Two groups were defined: (1) patients without LAAT, (2) patients with LAAT. The incidence of LAAT was 0.78% (13 of 1,658 patients). No LAAT was detected in patients with a CHA. The incidence of LAAT in patients scheduled for CA-AF is low. Therefore, periprocedural OAC strategies recommended by current guidelines seem feasible. Preprocedural TEE may be dispensed in patients with a CHA

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Catheter Ablation; Cohort Studies; Echocardiography, Transesophageal; Female; Humans; Incidence; Male; Middle Aged; Precision Medicine; Predictive Value of Tests; Risk Assessment; Stroke Volume; Thrombosis; Treatment Outcome; Vitamin K

The effectiveness of oral anticoagulation therapy with warfarin (a vitamin K antagonist) in the treatment of thromboembolic disease, including stroke prophylaxis in patients with atrial fibrillation is well recognised. However, warfarin has a narrow therapeutic window and an unpredictable anticoagulation response, which make it difficult to achieve and maintain optimal anticoagulation. Various dietary factors, including sudden changes in eating patterns, can significantly alter anticoagulation control, thereby potentially exposing patients to the risk of bleeding or thromboembolic complications. Dietary vitamin K intake is a particularly important factor, given the mechanism of action of warfarin. Areas covered: In this article, we cover the sources of vitamin K and their potential effect of dietary vitamin K on anticoagulation response to warfarin. We also discuss the results of studies on the effect of vitamin K supplementation on anticoagulation stability. Expert commentary: A stable dietary vitamin K, promoted by daily oral vitamin K supplementation, can improve anticoagulation stability in patients on warfarin therapy. There is experimental evidence in animals that dietary vitamin K affects anticoagulation response to the direct thrombin inhibitor, ximelagatran. Whether dietary vitamin K affects anticoagulation response to the currently licensed direct oral anticoagulants (DOACs) in man remains to be investigated.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Diet; Dietary Supplements; Food-Drug Interactions; Hemorrhage; Humans; Stroke; Thromboembolism; Vitamin K; Warfarin

Switching between oral anticoagulants and treatment discontinuation are common events related to therapy with non-vitamin K antagonist oral anticoagulants (NOACs). However, knowledge on the reasons leading to these treatment changes is scarce. The aim of this study was to identify clinical events preceding anticoagulant switching and NOAC discontinuation during oral anticoagulant therapy in patients with atrial fibrillation.. We performed a nationwide register-based study including Danish atrial fibrillation patients initiating a NOAC between August 2011 and February 2016 (n = 50 623). We explored potential reasons leading to changes in anticoagulant treatment by identifying clinical events preceding switches from vitamin K antagonists (VKA) to NOAC, switches from NOAC to VKA, and discontinuations of NOACs. Among 23 531 anticoagulant users changing treatment, we identified 13 295 switches from VKA to NOAC, 5206 switches from NOAC to VKA, and 8995 discontinuations of NOACs. Approximately half of all treatment changes were preceded by a hospitalization. A relevant specific clinical event or procedure was identified prior to 18.3% of switches from VKA to NOAC, prior to 23.0% of switches from NOAC to VKA, and prior to 26.6% of discontinuations. Switches from VKA to NOAC were most often preceded by thromboembolic events (7.0%), whereas cardioversion was the most common specific event prior to a switch from NOAC to VKA (11.4%). Discontinuations were most often preceded by bleeding events (7.6%).. For about one in five patients, treatment changes during anticoagulant therapy were preceded by a major clinical event. However, the majority of patients changed treatment for reasons not recorded in health registries.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Denmark; Drug Administration Schedule; Drug Substitution; Hemorrhage; Hospitalization; Humans; Registries; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hospitalization; Humans; Rivaroxaban; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hospitalization; Humans; Rivaroxaban; Vitamin K

Data highlighting the cost drivers for non-valvular atrial fibrillation (NVAF) patients in terms of vitamin K antagonist (VKA) treatment and monitoring are lacking in France. This study aimed to evaluate the real-life daily cost of VKA treatment in 2013, in French patients suffering from NVAF.. This longitudinal observational study was performed using the EGB (Echantillon Généraliste des Bénéficiaires) database, a random sample of the French national insurance (NHI) database, which covers 80% of the population. All adult patients whose first NVAF anticoagulant treatment in 2013 was a VKA were analyzed. Costs were calculated for the duration of follow-up and then divided by the number of days of therapy. The analysis was performed both from the French NHI perspective (amount reimbursed by the NHI) and from a collective perspective.. In this study, 3,254 NVAF patients treated with VKA in 2013 were included, and this sample comprised 52.6% males. The mean daily cost of VKA treatment was €1.13 (±1.18) according to the collective perspective (89.4% of this cost was associated to INR measurement) and €1.05 (±1.16) according to the NHI perspective.. As diagnoses associated with procedures are not available in the EGB database, proxies were used, and an algorithm was created to define the AF population.. This analysis is the first to consider an exhaustive spectrum of the costs of VKA treatment in France using EGB data. VKA medication requires exhaustive follow-up, and, thus, associated costs are important. The results of the present study confirmed this close follow-up for VKA patients, making the cost of treatment by VKA nearly 10-times more expensive than the cost of medication itself.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; France; Humans; Insurance Claim Review; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Office Visits; Prescription Fees; Vitamin K

It remains uncertain whether patients with atrial fibrillation (AF) requiring long-term oral anticoagulation (OAC) and with stable coronary artery disease (CAD) should receive antiplatelet therapy (APT) in addition to OAC.. APT in addition to OAC would be more effective than OAC alone in preventing ischaemic events in such patients.. In the international REduction of Atherothrombosis for Continued Health (REACH) Registry including 68 236 outpatients with or at risk for atherothrombosis, we identified 2347 patients with stable CAD and AF receiving vitamin K antagonists (VKA). Using propensity score matching, patients treated with VKA (n = 1481) were compared with those receiving VKA + APT at inclusion (n = 866). The primary outcome was major adverse cardiovascular events (MACE) at 4 years (cardiovascular death, myocardial infarction, or stroke). Secondary outcomes were all-cause death and bleeding leading to hospitalization and transfusion.. Patients receiving VKA only were older (74 vs 72 years, P < 0.01), had less diabetes (37% vs 42%, P = 0.02), and less frequent history of percutaneous coronary intervention (28.7% vs 43.9%, P < 0.01). The mean CHA. In this observational analysis, the use of APT in addition to OAC in patients with stable CAD and AF was not associated with lower risk of ischemic events but possibly with higher bleeding rates. Randomized trials are necessary to determine the optimal long-term antithrombotic strategy.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Coronary Artery Disease; Drug Administration Schedule; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Registries; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Chronic kidney disease (CKD) has been related to poor anticoagulation control and an increased risk of bleeding. This study aims to evaluate the association between impaired renal function (eGFR <60 mL/min/1.73 m. This is an ancillary analysis of 1381 patients from the PAULA study, which was a cross-sectional, retrospective and nationwide multicenter study.. Chronic kidney disease is associated with poor anticoagulation control in patients with non-valvular AF taking VKA. The SAMe-TT

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Vitamin K

The purpose of this study was to characterize the profile of patients with non-valvular atrial fibrillation who start an anticoagulant treatment after diagnosis with dabigatran and compare it with those who start with vitamin K antagonists (VKAs).. We analysed primary health care-based electronic health records data from 15,075 people with new diagnosis of atrial fibrillation who initiated treatment with dabigatran or VKA spanning 2011-2013. Logistic regression analysis for determination of factors associated with initiation of dabigatran was performed.. We identified 14,266 (94.6%) people who initiated VKA and 809 (5.4%) who initiated dabigatran. Mean age of people treated with dabigatran was lower than in VKA patients (73.7 vs 75.5 years, p < 0.001). People (90.5%) in VKA group and 83.6% in the dabigatran group had a high risk of stroke, according to CHA. Most patients recently diagnosed with non-valvular atrial fibrillation initiated treatment with VKA. Primary healthcare patients with non-valvular atrial fibrillation initiating dabigatran are younger, had a lower risk of stroke or bleeding, fewer comorbidity and more history of stroke and intracranial haemorrhage compared to those who were initiated on VKA.

Topics: Aged; Antithrombins; Atrial Fibrillation; Cross-Sectional Studies; Dabigatran; Electronic Health Records; Female; Humans; Logistic Models; Male; Treatment Outcome; Vitamin K

The ABC-stroke score (age, biomarkers [N-terminal fragment B-type natriuretic peptide, high-sensitivity troponin], and clinical history [prior stroke/transient ischemic attack]) was proposed to predict stroke in atrial fibrillation (AF). This score was derived/validated in 2 clinical trial cohorts in which patients with AF were highly selected and carefully followed-up. However, the median follow-up was 1.9 years in the trial cohort; therefore, its long-term predictive performance remains uncertain. This study aimed to compare the long-term predictive performances of the ABC-stroke and CHA. We recruited 1125 consecutive patients with AF who were stable on vitamin K antagonists and followed-up for a median of 6.5 years. ABC-stroke and CHA. In anticoagulated patients with AF followed-up over a long-term period, the novel ABC-stroke score does not offer significantly better predictive performance compared with the CHA

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Comorbidity; Decision Support Techniques; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Vitamin K

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Humans; Myocardial Infarction; Vitamin K

Direct oral anticoagulants (DOACs) have been promoted in patients with nonvalvular atrial fibrillation (nv-AF) as a more convenient alternative to vitamin K antagonists. We estimated 1-year dabigatran and rivaroxaban adherence rates in nv-AF patients and assessed associations between baseline patient characteristics and nonadherence.. This cohort study included OAC-naive nv-AF patients with no contraindications to OAC, who initiated dabigatran and rivaroxaban, using nationwide data from French national health care databases. One-year adherence was defined by the proportion of days covered of 80% or more over a fixed 1-year period after treatment initiation. Associations between nonadherence and baseline patient characteristics were assessed using multivariate logistic regression models.. The population was composed of 11 141 dabigatran (women: 48%; mean age: 74 ± 10.7 y; ≥80 y: 34.9%) and 11 126 rivaroxaban (46.5%; 74 ± 10.9 y; 34.8%) new users. One-year adherence was 53.3% in dabigatran-treated and 59.9% in rivaroxaban-treated patients, consistent with numerous subgroup analyses. A switch to vitamin K antagonist was observed in 14.5% of dabigatran and 11.7% of rivaroxaban patients; 10.2% and 5.9% of patients switched to another DOAC, respectively; and 4.3% of patients died in the 2 cohorts. In patients who did not die or switch during the follow-up, 1-year adherence was 69.6% in dabigatran-treated and 72.3% in rivaroxaban-treated patients. Having concomitant ischemic heart diseases was associated with an increased risk of nonadherence in the 2 cohorts.. In this real-life study, 1-year adherence to DOAC is poor in nv-AF new users. Despite the introduction of DOAC, adherence to OACs may remain a significant challenge in AF patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Dabigatran; Databases, Factual; Female; France; Health Care Surveys; Humans; Male; Medication Adherence; Middle Aged; Myocardial Ischemia; Rivaroxaban; Stroke; Vitamin K

The aim of this study was to describe persistence with vitamin K antagonist (VKA) treatment in German atrial fibrillation (AF) patients and to identify factors which may be associated with early discontinuation of VKA therapy.. We did a retrospective cohort study based on an anonymized German claims dataset with VKA treatment-naïve AF patients, who received at least one VKA prescription. VKA therapy discontinuation was defined as a gap >180 days.. We identified 38,076 VKA patients who started a VKA therapy (mean age 76.13 years; 56.08% female; mean CHA. Non-persistence related to VKA therapy is common in AF patients. Older more comorbid female patients as well as patients who face surgeries and who do not visit a cardiologist regularly face a higher therapy discontinuation risk.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Female; Germany; Humans; Male; Medication Adherence; Middle Aged; Retrospective Studies; Vitamin K; White People

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs).. A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants).. Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis.. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Balkan Peninsula; Female; Humans; Middle Aged; Prospective Studies; Risk Factors; Stroke; Surveys and Questionnaires; Vitamin K

Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABC-Bleeding score performed better than HAS-BLED score in a clinical trial cohort but has not been externally validated. The aim of this study was to analyze the predictive performance of the ABC-Bleeding score compared to HAS-BLED score in an independent "real-world" anticoagulated AF patients with long-term follow-up. We enrolled 1,120 patients stable on vitamin K antagonist treatment. The HAS-BLED and ABC-Bleeding scores were quantified. Predictive values were compared by c-indexes, IDI, NRI, as well as decision curve analysis (DCA). Median HAS-BLED score was 2 (IQR 2-3) and median ABC-Bleeding was 16.5 (IQR 14.3-18.6). After 6.5 years of follow-up, 207 (2.84 %/year) patients had major bleeding events, of which 65 (0.89 %/year) had intracranial haemorrhage (ICH) and 85 (1.17 %/year) had gastrointestinal bleeding events (GIB). The c-index of HAS-BLED was significantly higher than ABC-Bleeding for major bleeding (0.583 vs 0.518; p=0.025), GIB (0.596 vs 0.519; p=0.017) and for the composite of ICH-GIB (0.593 vs 0.527; p=0.030). NRI showed a significant negative reclassification for major bleeding and for the composite of ICH-GIB with the ABC-Bleeding score compared to HAS-BLED. Using DCAs, the use of HAS-BLED score gave an approximate net benefit of 4 % over the ABC-Bleeding score. In conclusion, in the first "real-world" validation of the ABC-Bleeding score, HAS-BLED performed significantly better than the ABC-Bleeding score in predicting major bleeding, GIB and the composite of GIB and ICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Atrial Fibrillation; Clinical Decision-Making; Decision Support Techniques; Disease-Free Survival; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Reproducibility of Results; Risk Assessment; Risk Factors; ROC Curve; Spain; Stroke; Time Factors; Treatment Outcome; Vitamin K

Ablation of atrial fibrillation (AF) on uninterrupted phenprocoumon reduces periprocedural thromboembolic and bleeding complications. Heparin is administered intraprocedurally to achieve activated clotting times (ACT) of 300-400 seconds. We investigated the effect of international normalized ratio (INR) on ACT and intraprocedural heparin requirements. Moreover, safety of a target ACT of 250-300 seconds was investigated.. We studied 949 patients referred for AF or left atrial tachycardia ablation. Patients were divided into Group 1 (n = 249) with an INR <2 and Group 2 (n = 700) with an INR ≥2. Mean INR was 1.7 ± 0.13 in Group 1 and 2.3 ± 0.25 in Group 2. Baseline, mean, minimum and maximum ACT were significantly lower in Group 1 (138 ± 17 seconds vs. 145 ± 21 seconds; 281 ± 28 seconds vs. 288 ± 29 seconds; 251 ± 36 seconds vs. 258 ± 34 seconds; 307 ± 32 seconds vs. 316 ± 40 seconds; P <0.05). Intraprocedural heparin requirements adjusted to body weight were lower in Group 1 (127 ± 41 U/kg vs. 122 ± 40 U/kg). Weak correlations between INR and baseline, mean, minimum and maximum ACT as well as intraprocedural heparin requirements were observed. No differences regarding major or minor complications were found. INR and periprocedural anticoagulation parameters had no influence on major complications. No thromboembolic complications were observed in both groups with a target ACT value of 250-300 seconds.. There is only a weak correlation between INR, intraprocedural ACT, and intraprocedural heparin requirements. Periprocedural target ACT of 250-300 seconds seems safe and does not increase periprocedural bleeding and thromboembolic complications in patients undergoing RF ablation on uninterrupted phenprocoumon therapy.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Catheter Ablation; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Vitamin K

To examine sex differences in thromboprophylaxis in patients with atrial fibrillation before and after the introduction of non-vitamin K oral anticoagulants, we performed a cross-sectional registry study based on anonymized individual-level patient data of all individuals with a diagnosis of nonvalvular atrial fibrillation (International Classification of Diseases, Tenth Revision code I48) in the region of Stockholm, Sweden (2.2 million inhabitants), in 2011 and 2015, respectively. Thromboprophylaxis improved considerably during the period. During 2007 to 2011, 23,198 men and 18,504 women had an atrial fibrillation diagnosis. In 2011, more men than women (53% men vs 48% women) received oral anticoagulants (almost exclusively warfarin) and more women received aspirin only (35% women vs 30% men), whereas there was no sex difference for no thromboprophylaxis (17%). During 2011 to 2015, 27,237 men and 20,461 women had a diagnosis of atrial fibrillation. Compared with the earlier time period, a higher proportion used oral anticoagulants (71% women vs 70% men), but fewer women ≥80 years received anticoagulants (67% women vs 72% men), more women received aspirin (15% women vs 13% men), and fewer women had no thromboprophylaxis (15% women vs 17% men). Patients with co-morbidities potentially complicating oral anticoagulant use used more oral anticoagulant in 2015 compared with 2011. The sex differences observed in 2011 with fewer women using oral anticoagulants had disappeared in 2015 except in women 80 years and older and in patients with complicated co-morbidity.

Topics: Administration, Oral; Adult; Age Distribution; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Prevalence; Registries; Retrospective Studies; Sex Distribution; Sex Factors; Stroke; Survival Rate; Sweden; Thrombolytic Therapy; Vitamin K; Young Adult

Data are limited on the safety of periprocedural anticoagulation with novel oral anticoagulants (NOACs) in patients undergoing pulmonary vein isolation (PVI) using the second-generation cryoballoon (CB) for the treatment of atrial fibrillation.. We hypothesized that the incidence of acute periprocedural complications in patients undergoing PVI do not differ between patients treated with VKA compared to NOACs.. In 200 consecutive patients (mean age, 64.3 _ 10.6 years; female, n = 83) with symptomatic atrial fibrillation, PVI using the second-generation 28-mm CB was performed. In patients treated with NOACs, the medication was stopped the day of the procedure and continued the evening after the procedure with a reduced dosage. Patients treated with phenprocoumon were continued on uninterrupted phenprocoumon with a target INR of 2 to 3. If INR was <2, bridging with low-molecular-weight heparin was performed.. Forty-seven of 200 patients (23.5%) were treated with a vitamin K antagonist (VKA) and 55 (27.5%) were treated with apixaban, 67 (33.5%) with rivaroxaban, and 31 (15.5%) with dabigatran. Seven (3.5%) major complications occurred in the overall population. Major bleeding complications did not differ significantly between the 2 groups (P = 0.23). One patient taking VKA had a pericardial tamponade at the end of the procedure; 2 patients treated with apixaban developed a groin hematoma requiring surgical intervention. Transient ischemic attack occurred in 1 patient of the apixaban and rivaroxaban group.. Apixaban, rivaroxaban, and dabigatran, compared with uninterrupted VKA, did not show a higher risk for major bleeding or ischemic complications in patients undergoing PVI using the second-generation CB.

Topics: Administration, Oral; Aged; Antithrombins; Atrial Fibrillation; Cardiac Catheters; Cerebrovascular Disorders; Cryosurgery; Dabigatran; Drug Administration Schedule; Drug Monitoring; Equipment Design; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Postoperative Hemorrhage; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Atrial Fibrillation; Female; Fibrinolytic Agents; Health Knowledge, Attitudes, Practice; Humans; Male; Medication Adherence; Middle Aged; Stroke; Surveys and Questionnaires; Vitamin K

The global real-life impact of non-vitamin K antagonist oral anticoagulants (NOACs) introduction in the healthcare system in a setting of well-managed vitamin K antagonist (VKA) therapy has not been specifically addressed.. We did a population-based retrospective cohort study in naïve patients initiating oral anticoagulants for stroke prevention in atrial fibrillation in a region with a well-managed VKA therapy. NOAC and VKA cohorts were identified using Anatomical Therapeutic Chemical (ATC) codes, while excluding other indications for anticoagulation therapy using ICD-9CM codes. Propensity score was conducted using two different approaches: stratification and 1:1 matching. Event-rates were assessed using both an intention to treat (ITT) and as treated analyses.. Of the 137,800 selected patients, 40,411 (6923 treated with NOACs and 33,488 with VKAs) were identified (June 2013-December 2015). Overall ischaemic stroke and major bleeding risk did not significantly differ between the groups both in the ITT and as treated analyses. Noteworthy, intracranial bleeding risk was lower with NOACs (stratified model HR=0.69; 95%CI 0.48-0.99; 1:1 matched model HR=0.73; 95%CI 0.47-1.13) reaching statistical significance in the as treated analysis in both stratified and 1:1 matched models (HR=0.51; 95%CI 0.32-0.80 and HR=0.52; 95%CI 0.30-0.90, respectively).. Despite well-managed anticoagulation with VKAs, NOACs' introduction has a positive global impact in the public healthcare system in terms of effectiveness and safety especially by lowering intracranial bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Disease Management; Female; Hemorrhage; Humans; Male; Middle Aged; Propensity Score; Retrospective Studies; Treatment Outcome; Vitamin K

Studies on long-term utilization of non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) are scarce. We evaluated predictors of use and long-term persistence of NOACs in a real-world setting.. This population-based cohort study used the computerized databases of the Canadian Province of Quebec's health insurance. Patients with a first NVAF diagnosis from 2011 until 2014 were included. A logistic regression model yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of treatment initiation with NOACs versus VKAs. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% CIs for predictors of switching from VKAs to NOACs versus remaining on VKAs, and for predictors of discontinuation of anticoagulation treatment.. Of the 62 867 newly diagnosed NVAF patients, 14 646 initiated NOACs and 17 685 VKAs. Initiation with NOACs was less likely for patients ≥ 80 years old (OR 0.55, 95% CI 0.41-0.73) or with CHA. Older, high-risk patients are less likely to initiate NOACs than VKAs. NOAC users show a higher long-term persistence than VKA users, and older, high-risk patients are less likely to discontinue anticoagulation treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quebec; Risk Factors; Thrombosis; Vitamin K

This study examined characteristics and treatment persistence among patients prescribed oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). We identified 15,244 patients (51.8% male, 72.7% aged ≥70) with NVAF and no prior OAC therapy who were prescribed apixaban (n = 1,303), rivaroxaban (n = 5,742), dabigatran (n = 1,622) or vitamin-K antagonists (VKAs, n = 6,577) between 1-Dec-2012 and 31-Oct-2014 in German primary care (IMS® Disease Analyzer). We compared OAC persistence using Cox regression over patients' entire follow-up and using a data-driven time-partitioned approach (before/after 100 days) to handle non-proportional hazards. History of stroke risk factors (stroke/transient ischaemic attack [TIA] 15.2%; thromboembolism 14.1%; hypertension 84.3%) and high bleeding risk (HAS-BLED score≥3 68.4%) was common. Apixaban-prescribed patients had more frequent history of stroke/TIA (19.7%) and high bleeding risk (72.6%) than other OACs. 12-month persistence rates were: VKA 57.5% (95% confidence interval (CI) 56.0-59.0%), rivaroxaban 56.6% (54.9-58.2%), dabigatran 50.1% (47.2-53.1%), apixaban 62.9% (58.8-67.0%). Over entire follow-up, compared to VKA, non-persistence was similar with apixaban (adjusted hazard ratio 1.08, 95% CI 0.95-1.24) but higher with rivaroxaban (1.21, 1.14-1.29) and dabigatran (1.53, 1.40-1.68). Using post-hoc time-partitioned approach: in first 100 days, non-persistence was higher with apixaban (1.37, 1.17-1.59), rivaroxaban (1.41, 1.30-1.53) and dabigatran (1.91, 1.70-2.14) compared to VKA. Compared to apixaban, rivaroxaban non-persistence was similar (1.03, 0.89-1.20), dabigatran was higher (1.39, 1.17-1.66). After 100 days, apixaban non-persistence was lower than VKA (0.66, 0.52-0.85); rivaroxaban (0.97, 0.87-1.07) and dabigatran (1.10, 0.95-1.28) were similar to VKA. Furthermore, rivaroxaban (1.46, 1.13-1.88) and dabigatran (1.67, 1.26-2.19) non-persistence was higher than apixaban. This study describes real-world observations on OAC use, particularly early apixaban use following approval for NVAF, in Germany. We identified potential differential OAC prescribing and higher persistence with apixaban than other OACs after 100 days' treatment. Larger studies are needed with longer follow-up to establish long-term patterns.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Germany; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Male; Primary Health Care; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Vitamin K

To better appreciate the role of the non-vitamin K oral anticoagulants (NOACs) for patients with non-valvular atrial fibrillation in Switzerland we aimed to assess the quality of vitamin K antagonist (VKA) anticoagulation in daily practice.. In a cross-sectional study, clinically stable patients on VKA treatment for non-valvular atrial fibrillation for at least 6 months, documentation of international normalised ratio (INR) values for at least 3 months and with at least two INR values were included. The percentage of INR values within the therapeutic range of 2.0 to 3.0 and the time in therapeutic range (TTR; Rosendaal method) and predictors for these measures of VKA anticoagulation quality were assessed.. We studied 332 patients (62% male, mean age 74 ± 9 years) with median (interquartile range) CHA2DS2Vasc and HAS-BLED scores of 4 (3-5) and 3 (2-4) points. The median number of INR values per patient was 8 (5-14), and the average interval between INR measurements was 20 (13-27) days. The percentage of INR values between 2.0 and 3.0 was 67% (50-83%). The median TTR was 69% (51-89%), and TTR ≥65% was found in 202 (61%) patients. Independent predictors of ≥80% INR values between 2.0 and 3.0 included a longer interval between INR measurements and the non-use of spironolactone. The non-use of amiodarone and spironolactone and a longer interval between INR measurements were the only independent predictors of a TTR ≥65%.. The quality of VKA anticoagulation in Switzerland is highly variable. Importantly, only 60% of patients achieve a TTR ≥65%, which is currently considered to be the minimal acceptable TTR required for VKA therapy. There are few clinical predictors of a good VKA anticoagulation quality. These data may represent a novel basis for decision making regarding the choice of anticoagulation for atrial fibrillation in Switzerland.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cross-Sectional Studies; Female; Humans; International Normalized Ratio; Male; Surveys and Questionnaires; Switzerland; Vitamin K

The prevalence of atrial fibrillation (AF) is high in elder subjects. Our previous observational study suggested that vitamin K antagonist (VKA) promotes aortic valve degeneration, a principal cause of aortic stenosis in the elderly, and that angiotensin receptor blocker (ARB) attenuates its progression. This study aimed to prospectively investigate these observations in non-valvular AF patients.. Of enrolled 430 patients with calcification on no or one aortic valve leaflet, all of the planned 4-year follow-up data were obtained in 122 non-valvular AF patients treated with warfarin (warfarin group) and 101 patients with cardiovascular diseases and without AF and prescription of warfarin (non-warfarin group).. Despite higher atherosclerotic risks in the non-warfarin group, 2 or 3 newly calcified leaflets emerged during 4years in 18.0% of patients in the warfarin group and in 6.9% in the non-warfarin group (p=0.014). Aortic valve area (AVA) did not significantly change in the non-warfarin group during the follow-up, but tended to decrease in the warfarin group (p=0.057). Non-vitamin K antagonist oral anticoagulant got available in Japan after this study started, and warfarin was discontinued in 15 patients of the warfarin group. The reduction of AVA was significant in the remaining 107 patients on the continuous warfarin treatment (p=0.002). The effects of ARB on AVA were obscure.. Major bleeding associated with VKA is well recognized. This study suggests that the development of aortic valve degeneration is another risk of long-term use of VKA in non-valvular AF patients with no or mild aortic valve degeneration.

Topics: Aged; Aortic Valve; Atrial Fibrillation; Echocardiography; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Time Factors; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with high rates of death, ischemic stroke and systemic embolism (SE). There is scarce information about clinical characteristics and use of anti-thrombotic therapies in Chilean patients with non-valvular AF.. To describe the characteristics and 1-year outcomes of patients with recently diagnosed AF recruited in Chile into the prospective global GARFIELD-AF registry.. Between 2011-2016, we prospectively registered information of 971 patients recruited at 15 centers, 85% of them from the public system and 15% from the private sector. Demographics, clinical characteristics and use of antithrombotic therapies were recorded for all patients. Adverse clinical outcomes were analyzed in 711 patients with 1-year follow-up.. The mean age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral anticoagulants were prescribed in 82% of patients. Seventy percent received Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy and only 8% did not receive any antithrombotic therapy. Mean time in optimal therapeutic range (an international normalized ratio of 2 to 3), was achieved in only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40 (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up.. Although the use of vitamin K antagonists at baseline was high, the mean time in optimal therapeutic range was low. Mortality and stroke rates are higher than those reported in other contemporary registries.

Topics: Aged; Antithrombins; Atrial Fibrillation; Chile; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stroke; Time Factors; Vitamin K

Management strategies for patients with atrial fibrillation (AF) in association with valvular heart disease (VHD) have been less informed by randomized trials, which have largely focused on ‘non-valvular AF’ patients. Thromboembolic risk also varies according to valve lesion and may also be associated with CHA2DS2-VASc score risk factor components, rather than only the valve disease being causal.\ \ Given the need to provide expert recommendations for professionals participating in the care of patients presenting with AF and associated VHD, a task force was convened by the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group (WG) on Thrombosis, with representation from the ESC WG on Valvular Heart Disease, Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE) with the remit to comprehensively review the published evidence, and to produce a consensus document on the management of patients with AF and associated VHD, with up-to-date consensus statements for clinical practice for different forms of VHD, based on the principles of evidence-based medicine.\ \ This is an executive summary of a consensus document which proposes that the term ‘valvular AF’ is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional EHRA (Evaluated Heartvalves, Rheumatic or Artificial) categorization in relation to the type of OAC use in patients with AF, as follows: (1) EHRA (Evaluated Heartvalves, Rheumatic or Artificial) type 1 VHD, which refers to AF patients with ‘VHD needing therapy with a vitamin K antagonist (VKA)’ and (2) EHRA (Evaluated Heartvalves, Rheumatic or Artificial) type 2 VHD, which refers to AF patients with ‘VHD needing therapy with a VKA or a non-VKA oral anticoagulant also taking into consideration CHA2DS2-VASc score risk factor components.

Topics: Administration, Oral; Africa, Southern; Asia; Atrial Fibrillation; Europe; Evidence-Based Medicine; Expert Testimony; Fibrinolytic Agents; Heart Valve Diseases; Humans; Latin America; Practice Guidelines as Topic; Risk; Stroke; Vitamin K

The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.. Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA. In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Topics: Acute Disease; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dabigatran; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Survival Rate; Time Factors; Treatment Outcome; Vitamin K

Following their introduction, the non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly prescribed in Asia for stroke prevention in patients with non-valvular atrial fibrillation (AF). Few contemporary data are available on temporal trends in antithrombotic therapy use in Asian countries, in the era of NOACs.. Using the National Health Insurance Service database of the entire Korean adult AF population, the use of aspirin, vitamin K antagonist, and NOACs between 2008 and 2015 were analyzed (n = 276,246 in 2015). Most of the included cohort had CHA2DS2-VASc score ≥ 2 (78.2% in 2008 and 83.2% in 2015), yet approximately 17% were prescribed no antithrombotic therapy throughout the study period. Aspirin prescription consistently decreased (from 48.2% to 31.5%) over time, while OAC prescription significantly increased from 34.7% to 50.6%. NOAC prescriptions accounted for 50% of total OAC prescription in 2015. Similar trends in antithrombotic therapy were found both in men and in women, but women were more likely to be undertreated with OAC. Female gender, presence of vascular disease and prior intracranial hemorrhage were associated with OAC underuse.. Between 2008 and 2015, a greater proportion of AF patients received OAC treatment with increasing NOAC prescription trends in the recent 3 years. A substantial proportion (approx. 50%) of Korean patients with AF still remain undertreated.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Republic of Korea; Stroke; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Atrial Fibrillation; Combined Modality Therapy; Humans; Indenes; Intraoperative Period; Observational Studies as Topic; Postoperative Hemorrhage; Risk Factors; Surgical Procedures, Operative; Venous Thromboembolism; Vitamin K

To determine the differences between regions in the level of control of patients with non-valvular atrial fibrillation treated with vitamin K antagonists, included in the PAULA study.. Observational, and coss-sectional/retrospective study, including 139 Primary Care physicians from 99 Health Care centres in all autonomous communities (except La Rioja). Anticoagulation control was defined as the time in therapeutic range assessed by either the direct method (poor control <60%), or the Rosendaal method (poor control <65%).. A total of 1,524 patients were included. Small differences in baseline characteristics of the patients were observed. Differences in the percentage of time in therapeutic range were observed, according to the Rosendaal method (mean 69.0±17.7%), from 78.1%±16.6 (Basque Country) to 61.5±14% (Balearic Islands), by the direct method (mean 63.2±17.9%) from 73.6%±16.6 (Basque Country) to 57.5±15.7% (Extremadura). When comparing regions, in those where the Primary Care physicians assumed full control without restrictions on prescription, the percentage of time in therapeutic range by the direct method was 63.89 vs. 60.95% in those with restrictions (p=.006), by Rosendaal method, 69.39% compared with 67.68% (p=.1036).. There are significant differences in the level of control between some regions are still inadequate. Regions in which the Primary Care physicians assumed the management of anticoagulation and without restrictions, time in therapeutic range was somewhat higher, and showed a favourable trend for better control. These findings may have clinical implications, and deserve consideration and specific analysis.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; International Normalized Ratio; Male; Physicians, Primary Care; Primary Health Care; Retrospective Studies; Spain; Time Factors; Vitamin K

The use of non-vitamin K antagonists (NOACs), uninterrupted (uVKA) and interrupted vitamin K antagonists (iVKA) are common periprocedural oral anticoagulation (OAC) strategies for atrial fibrillation (AF) ablation. Comparative data on complication rates resulting from OAC strategies for solely persistent AF (persAF) undergoing ablation are sparse. Thus, we sought to determine the impact of these OAC strategies on complication rates among patients with persAF undergoing catheter ablation.. Consecutive patients undergoing persAF ablation were included. Depending on preprocedural OAC, three groups were defined: (1) NOACs (paused 48 h preablation), (2) uVKA, and (3) iVKA with heparin bridging. A combined complication endpoint (CCE) composed of bleeding and thromboembolic events was analyzed.. Between 2011 and 2014, 1440 persAF ablation procedures were performed in 1092 patients. NOACs were given in 441 procedures (31 %; rivaroxaban 57 %, dabigatran 33 %, and apixaban 10 %), uVKA in 488 (34 %), and iVKA in 511 (35 %). Adjusted CCE rates were 5.5 % [95 % confidence interval (CI) (3.1-7.8)] in group 1 (NOACs), 7.5 % [95 % CI (5.0-10.1)] in group 2 (uVKA), and 9.9 % [95 % CI (6.6-13.2)] in group 3. Compared to group 1, the combined complication risk was almost twice as high in group 3 [odd's ratio (OR) 1.9, 95 % CI (1.0-3.7), p = 0.049)]. The major complication rate was low (0.9 %). Bleeding complications, driven by minor groin complications, are more frequent than thromboembolic events (n = 112 vs. 1, p < 0.0001).. Patients undergoing persAF ablation with iVKA anticoagulation have an increased risk of complications compared to NOACs. Major complications, such as thromboembolic events, are generally rare and are exceeded by minor bleedings.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Drug Administration Schedule; Female; Humans; Length of Stay; Linear Models; Male; Middle Aged; Odds Ratio; Perioperative Care; Postoperative Hemorrhage; Retrospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K

Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non-VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one-third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Denmark; Drug Substitution; Drug Utilization Review; Female; Hemorrhage; Humans; Male; Middle Aged; Registries; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse.. To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF.. Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks.. Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%).. Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dabigatran; Denmark; Female; Hospitalization; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Vitamin K; Warfarin

Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome.. Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium.. Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment.. A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Splanchnic Circulation; Venous Thrombosis; Vitamin K; Young Adult

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Consensus; Coronary Artery Disease; Drug Substitution; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Stents; Thrombosis; Vitamin K

Limited data are available on major bleeding (MB) occurring during treatment with vitamin K (VKAs) or direct oral anticoagulants (DOACs) outside clinical trials.. Patients hospitalized for MB while on treatment with VKAs or DOACs were included in a multicenter study to compare clinical presentation, management and outcome of bleeding. The primary study outcome was death at 30days.. Between September 2013 and September 2015, 806 patients were included in the study, 76% on VKAs and 24% on DOACs. MB was an intracranial hemorrhage in 51% and 21% patients on VKAs or DOACs, respectively (Odds Ratio [OR] 3.79; 95% confidence interval [CI] 2.59-5.54) a gastrointestinal bleeding in 46% and 25% patients on DOACs and VKAs, respectively (OR 2.62; 95% CI 1.87-3.68). Death at 30days occurred in 130 patients (16%), 18% and 9% of VKA and DOAC patients (HR 1.95; 95% CI 1.19-3.22, p=0.008). The rate of death at 30days was similar in VKA and DOAC patients with intracranial hemorrhage (26% and 24%; HR 1.05, 95% CI 0.54-2.02) and gastrointestinal bleeding (11% and 7%; HR 1.46, 95% CI 0.57-3.74) and higher in VKA than DOAC patients with other MBs (10% and 3%; HR 3.42, 95% CI 0.78-15.03).. Admission for ICH is less frequent for DOAC patients compared with VKA patients. Admission for gastrointestinal MB is more frequent for DOAC as compared to VKA patients. Mortality seems lower in patients with MBs while on DOACs than VKAs but this finding varies across different types of MBs.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Survival Rate; Venous Thromboembolism; Vitamin K

The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions.. We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes.. We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADS. This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Cohort Studies; Databases, Factual; Electronic Health Records; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Primary Health Care; Proportional Hazards Models; Retrospective Studies; Spain; Stroke; Treatment Outcome; Vitamin K

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Stroke; Treatment Outcome; Vitamin K

The aims of this study were to assess the impact of atrial fibrillation (AF) on outcome in transfemoral aortic valve replacement (TAVR) and to evaluate the safety and efficacy of apixaban compared with a vitamin K antagonist (VKA) in patients with AF after TAVR.. Non-VKA oral anticoagulant agents have not been systematically used in patients with AF after TAVR.. Of the 617 patients enrolled, 55.9% (n = 345) were in sinus rhythm and 44.1% (n = 272) in AF. Clinical follow-up was performed after 30 days and 12 months.. The early safety endpoint at 30 days was significantly more frequent in patients with AF compared with those in sinus rhythm (23.2% vs. 11.0%; p < 0.01). During 12-month follow-up, the secondary endpoint of all-cause mortality and stroke was significantly higher in patients with AF (20.6% vs. 9.7%; p = 0.02), driven by a significantly higher rate of all-cause mortality (19.1% vs. 7.8%; p = 0.01). Among patients with AF, 141 (51.8%) were treated with apixaban and 131 (48.2%) with a VKA. There was a significantly lower rate of the early safety endpoint in patients with AF treated with apixaban compared with patients treated with a VKA (13.5% vs. 30.5%; p < 0.01), with a numerically lower stroke rate (2.1% vs. 5.3%; p = 0.17) at 30 days and 12 months (1.2% vs. 2.0%; p = 0.73) of follow-up.. In patients undergoing TAVR, AF was associated with a significantly higher rate of all-cause mortality throughout 12 months follow-up. The early safety endpoint in patients with AF on apixaban was significantly less frequent compared with patients receiving a VKA.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease-Free Survival; Factor Xa Inhibitors; Female; Femoral Artery; Humans; Kaplan-Meier Estimate; Male; Phenprocoumon; Proportional Hazards Models; Prospective Studies; Punctures; Pyrazoles; Pyridones; Registries; Risk Factors; Stroke; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Persistence to treatment affects clinical outcomes in patients with chronic disease such as atrial fibrillation (AF).. This prospective cohort study included consecutive non-valvular AF patients prescribed with non-vitamin K oral anticoagulants (NOACs) and investigated for any permanent discontinuation at 1-year of this therapy, as well as any reasons for discontinuation.. Overall, 1305 patients were prescribed with dabigatran (N=473), rivaroxaban (N=425) or apixaban (N=407). Of these, 201 patients (15.4%) discontinued NOACs during the first year of treatment. More than 60% of these discontinuations occurred during the first 6months. Reasons for discontinuation included: dyspepsia or abdominal pain in 38 patients (2.9%) and bleeding in 59 (4.5%). Discontinuation for the former occurred earlier (50% within 2months) compared to the latter (66% after the first 4months). The prescription of reduced NOAC doses resulted being an independent predictor of discontinuation (OR 1.74, 95% CI 1.23-2.45, p=0.002). Regarding the use of dabigatran, rivaroxaban and apixaban, the following were observed: discontinuers were 22.0% (95% CI 18.5-25.9), 14.4% (95% CI 11.3-18.0) and 8.8% (95% CI 6.5-12.0), the risk of discontinuation associated with bleeding was 20.2%, 44.3% and 30.6% and dyspepsia or abdominal pain was 35.6%, 1.6% and 0%, respectively.. Discontinuation of NOACs in AF patients was relatively common and more than often occurred in the first six months after prescription. Patients treated with reduced doses of NOACs had a higher probability to discontinue compared to those who were prescribed conventional doses.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Dyspepsia; Female; Follow-Up Studies; Hemorrhage; Humans; Italy; Male; Medication Adherence; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Vitamin K

The purpose of this study was to describe adherence with non-vitamin K antagonists (NOACs) and vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (NVAF).. By linkage of Danish nationwide registers, we identified patients with NVAF who claimed a prescription of a NOAC (dabigatran, rivaroxaban, and apixaban), or a VKA. Adherence was evaluated according to Proportions of Days Covered, refill gaps, and switch in treatment. Adjusted analyses were calculated with logistic regression and Cox proportional hazard models. Between 2011 and 2014, 46 675 patients with NVAF claimed a prescription of anticoagulation (OAC): 57.3% used VKA, 29.8% dabigatran, 8.5% rivaroxaban, and 4.4% apixaban. During the first 180 days, PDC >80% was the highest among users of rivaroxaban. Compared with rivaroxaban, OR was 0.79 with apixaban (95% CI 0.69-0.92), 0.72 with dabigatran (95% CI 0.66-0.80), and 0.76 with VKAs (95% CI 0.69-0.83). HR for refill gaps between 7 and 89 days of length were (rivaroxaban as reference): apixaban 1.52(95% CI 1.36-1.69), dabigatran 1.72 (95% CI 1.60-1.85), and VKA 2.36(95% CI 2.20-2.52). Refill gaps of more than 89 days occurred in 11.5% of VKA recipients, with substantially lower rates for patients treated with NOAC. Switch between OACs was the highest in users of dabigatran (21.0%) and the lowest in users of apixaban (8.6%).. Among NVAF patients treated with OAC, 42.7% received a NOAC. PDC > 80%, and periods without refill gaps were the highest among users of rivaroxaban. Refill gaps occurred most often with VKA, switch was most common with dabigatran use.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Denmark; Female; Humans; Incidence; Male; Middle Aged; Registries; Stroke; Thrombolytic Therapy; Vitamin K; Young Adult

Some patients with atrial fibrillation (AF) received underdoses of non-vitamin K antagonist oral anticoagulants (NOACs) in the real world. Underdosing is defined as administration of a dose lower than the manufacturer recommended dose.. To identify the efficacy and safety of underdosing NOACs as perioperative anticoagulation for atrial fibrillation ablation.. We retrospectively analyzed patients who received rivaroxaban or dabigatran etexilate according to dosage: adjusted low dosage (reduced by disturbed renal function; n = 30), underdosage (n = 307), or standard dosage (n = 683). Non-vitamin K antagonist oral anticoagulants and dosing decisions were at the discretion of treating cardiologists.. Patients who received underdosed NOACs were older, more often female, and had lower body weight and lower renal function than those who received standard dosages. Activated clotting time at baseline in patients who received adjusted low dosage or underdosages was slightly longer than that in patients receiving standard dosages (156 ± 23, 151 ± 224, and 147 ± 24 seconds, respectively). Meaningful differences were not observed in other coagulation parameters. Adjusted low-, under-, and standard-dosing regimens did not differ in perioperative thromboembolic complications (0/30, 0.0%; 1/307, 0.3%; and 0/683, 0%, respectively) or major (0/30, 0.0%; 2/307, 0.6%; 3/683, 0.4%) and minor (1/30, 3.3%; 13/307, 4.2%; 25/683, 3.6%) bleeding episodes. When comparisons were performed for each NOAC, similar results were observed.. With consideration of patient condition, age, sex, body weight, body mass index, and renal function, underdosing NOACs was effective and safe as a perioperative anticoagulation therapy for atrial fibrillation ablation. The therapeutic range of NOACs is potentially wider than manufacturer recommendations.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Perioperative Care; Retrospective Studies; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K

Nonvitamin K antagonist oral anticoagulants (NOACs) are now available for the prevention of stroke in patients with atrial fibrillation (AF) as an alternative to vitamin K antagonists (VKA) and aspirin. The comparative effectiveness and safety in daily practice of these different drug classes is still unclear. The objective of this study was to evaluate the risk of major bleeding and stroke in AF patients using NOACs, VKAs or aspirin.. A retrospective cohort study was conducted among AF patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). New users of VKAs, NOACs and low dose aspirin were followed from the date of first prescription of an antithrombotic drug until the occurrence of stroke or major bleeding. Analyses were adjusted for a history of comorbidities and drug use with Cox regression analysis.. A total of 31 497 patients were eligible for the study. The hazard ratio (HR) of major bleeding was 2.07 [95% confidence interval (CI) 1.27-3.38] for NOACs compared with VKAs, which was mainly attributed by the increased risk of gastrointestinal bleeding (HR 2.63, 95% CI 1.50-4.62). This increased bleeding risk was restricted to women (HR 3.14, 95% CI 1.76-5.60). Aspirin showed a similar bleeding risk as VKAs. NOACs showed equal effectiveness as VKA in preventing ischaemic stroke (HR 1.22, 95% CI 0.67-2.19). VKAs were more effective than aspirin (HR 2.18, 95% CI 1.83-2.59).. NOACs were associated with a higher risk on gastrointestinal bleeding, particularly in women. The use of NOACs in patients who are vulnerable for this type of bleeding should be carefully considered. NOACs and VKAs are equally effective in preventing stroke. Aspirin was not effective in the prevention of stroke in AF.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Creatinine; Embolism; Factor Xa Inhibitors; Humans; Kidney; Kidney Function Tests; Rivaroxaban; Stroke; Vitamin K; Warfarin

Apixaban, dabigatran and rivaroxaban are three new direct oral anticoagulants (DOACs) used in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) in Spain.. To assess the relative cost-utility of the three DOACs compared with vitamin K antagonists.. A Markov model with 3-month cycles was used to simulate NVAF patients starting with treatment and followed up for their lifetime from the perspective of the National Health System. The model included 36 health states including treatment combinations, disability and events history and considered a hypothetical cohort of 10,000 NVAF patients. Relative efficacy was calculated from a formal indirect treatment comparison using data from the pivotal trials of each DOAC.. Dabigatran was associated with the highest number of quality-adjusted life years (QALY) (8.40 QALY), followed by apixaban (8.33 QALY), rivaroxaban (8.15 QALY) and acenocoumarol (8.03 QALY). Patients taking acenocoumarol had the lowest total costs (€22,230), followed by dabigatran (€24,564), apixaban (€24,655) and rivaroxaban (€25,900). Incremental cost-utility ratios compared to vitamin K antagonists, were €6,397, €8,039 and €29,957/QALY for dabigatran, apixaban and rivaroxaban, respectively. If compared together, dabigatran dominated apixaban and rivaroxaban. Sensitivity analyses confirmed the robustness of the baseline case.. All three direct anticoagulants are cost-effective against acenocoumarol. Dabigatran is economically dominant over rivaroxaban and apixaban in the Spanish setting, as it is more effective and cheaper.. Comparacion del coste-utilidad de los anticoagulantes orales de accion directa en la prevencion de ictus en la fibrilacion auricular no valvular en España.. Introduccion. El apixaban, el dabigatran y el rivaroxaban son tres anticoagulantes orales de accion directa (ACOD) indicados para la prevencion del ictus y la embolia sistemica en pacientes con fibrilacion auricular no valvular (FANV) en España. Objetivo. Comparar el coste-utilidad de los tres ACOD frente a los antivitamina K. Pacientes y metodos. Se utilizo un modelo Markov con ciclos trimestrales para simular pacientes con FANV desde que inician su tratamiento hasta el resto de su vida desde la perspectiva del Sistema Nacional de Salud. El modelo incorporo 36 estados de salud, incluyendo combinaciones de tratamientos, discapacidad y antecedentes de eventos, y considero una cohorte hipotetica de 10.000 pacientes con FANV. La eficacia relativa se calculo a partir de una comparacion indirecta formal de los tratamientos segun los datos de los ensayos pivotales de cada ACOD. Resultados. El dabigatran se asocio al valor maximo de años de vida ajustados por calidad (AVAC) (8,40 AVAC), seguido del apixaban (8,33 AVAC), el rivaroxaban (8,15 AVAC) y el acenocumarol (8,03 AVAC). Los costes totales fueron menores con el acenocumarol (22.230 €), seguido del dabigatran (24.564 €), el apixaban (24.655 €) y el rivaroxaban (25.900 €). La ratio coste-utilidad incremental frente a los antivitamina K fue de 6.397, 8.039 y 29.957 €/AVAC para el dabigatran, el apixaban y el rivaroxaban, respectivamente. Comparados entre ellos, el dabigatran domino al apixaban y al rivaroxaban. Los analisis de sensibilidad confirmaron la robustez del caso base. Conclusiones. Los tres ACOD son coste-efectivos frente al acenocumarol. El dabigatran es economicamente dominante frente al rivaroxaban y al apixaban en España, al ser mas efectivo y menos costoso.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Female; Humans; Male; Markov Chains; Pyrazoles; Pyridones; Rivaroxaban; Spain; Stroke; Vitamin K

Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: Background It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated. Results Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203-430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP < 400. Conclusion In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Cross-Sectional Studies; Drug Monitoring; Female; Hemophilia A; Hemostasis; Humans; International Normalized Ratio; Kinetics; Male; Middle Aged; Phenprocoumon; Severity of Illness Index; Thrombin; Vitamin K; Young Adult

The vitamin K antagonists (VKAs) are currently the most effective therapeutic class for the prevention of cerebrovascular eventsin atrial fibrillation (AF) patients. However, several studies showed an under-prescription of this therapy.The aim of the study was to assess the prescription of VKAs in non-valvular AF (NVAF) patients and factors influencing the non-prescription ofsuch treatment.. We conducted a prospective, observational study in an emergency department (ED). Patients with high thromboembolic risk NVAFand not receiving VKAs beforehand were included. Calculation of CHA2DS2-VASc and HAS-BLED scores was performed. An analytic study wasconducted in order to identify independent predictors of the under-prescription of VKAs.. During study, 176 patients were enrolled, the mean age was 67±13 years and 66% were women. The mean CHA2DS2VASc andHASBLED scores were 2.88 ± 1.55 and 1.52 ± 1.05, respectively. Among our cohort, VKA was prescribed in 36% of cases. Age >70 years(OR=1.59, 95%CI[1.11-2.21],p<0.001), creatinine level ≥110 μmol/l (OR=2.54,95%CI[1.20-5.37],p=0.01) and aspirin use (OR =1.7,95%CI [1.08-2.67],p=0.02) were independently associated with under-prescription of VKAs. Bedside, the main causes reported by the emergency physicians(EP) were: factors related to patient characteristics (n=38,34%), factors related to emergency physician (n=62,55%), factors related to the patientenvironment (n=20,17%) and factors related to the drug (n=22,23%).. Our results showed that the prescription of VKAs was low in ED. The reasons of VKA under-prescription are linked usually toseveral factors inherent to patient and to the adherence of EP to new recommendations.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Prospective Studies; Stroke; Vitamin K