vitamin-k-semiquinone-radical and Stroke

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

Patients undergoing transcatheter aortic valve implantation (TAVI) commonly have co-morbidities requiring anticoagulation. However, the optimal post-procedural anticoagulation regimen is not well-established. This meta-analysis investigates safety and efficacy outcomes of direct oral anticoagulants (DOACs) and Vitamin K Antagonist (VKA), with or without concomitant antiplatelet therapy. We searched EMBASE and MEDLINE for appropriate studies. Subgroup analyses were performed for anticoagulant monotherapy and combined therapy with antiplatelet agents. Eleven studies (6359 patients) were included. Overall, there were no differences between DOACs and VKA for all-cause mortality (Odds Ratio [OR]: .69; Credible Interval [CrI]: .40-1.06), cardiovascular-related mortality (OR: .76; Crl: .13-3.47), bleeding (OR: .95; CrI: .75-1.17), stroke (OR: 1.04; CrI: .65-1.63), myocardial infarction (OR: 1.51; CrI: .55-3.84), and valve thrombosis (OR: .29; CrI: .01-3.54). For DOACs vs VKA monotherapy subgroup, there were no differences in outcomes. For the combined therapy subgroup, there was decreased odds of all-cause mortality in the DOACs group compared with the VKA group (OR: .13; CrI: .02-.65), but no differences for bleeding and stroke. DOACs and VKA have similar safety and efficacy profiles for post-TAVI patients with anticoagulation indication. However, if concomitant antiplatelet therapy is required, DOACs were more favorable than VKA for all-cause mortality.

Topics: Administration, Oral; Anticoagulants; Bayes Theorem; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Stroke; Transcatheter Aortic Valve Replacement; 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

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

Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from "standard" care.. Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in "high-risk" patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of L-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance. Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.

Topics: Anticoagulants; COVID-19; Fibrinolytic Agents; Humans; Migraine Disorders; Stroke; 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

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

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

Direct oral anticoagulants (DOACs) are the guideline-recommended therapy for some hypercoagulable diseases but are used off-label for left ventricular thrombus (LVT) owing to a paucity of evidence. We performed a meta-analysis to assess the safety and efficacy of DOACs compared with vitamin K antagonists (VKAs) for LVT treatment.. We comprehensively searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for studies that compared DOACs with VKAs for LVT treatment. Outcome indicators included stroke or systemic embolism (SSE), thrombus resolution, bleeding, and death. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. Data were analyzed using Review Manager 5.3, and the meta-analysis is registered at PROSPERO (CRD 42020211376).. We included 12 observational studies (n = 2262 patients). SSE was similar for DOACs and VKAs groups (odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.66-1.54, P = 0.95). For thrombus resolution, DOACs were not significantly different to VKAs (OR = 1.15, 95% CI 0.54-2.45, P = 0.71). DOACs and VKAs had a similar bleeding risk (OR = 0.78, 95% CI 0.45-1.35, P = 0.37). DOACs and VKAs groups had a comparable mortality (OR = 0.91, 95% CI 0.50-1.65, P = 0.76). Subgroup analysis showed that post-acute myocardial infarction (AMI) patients using DOACs had a lower risk of SSE (OR = 0.24, 95% CI 0.07-0.87, P = 0.03) and bleeding (OR = 0.38, 95% CI 0.18-0.81, P = 0.01).. DOACs and VKAs showed no difference in the safety and efficacy of patients with LVT. DOACs might be superior to VKAs for LVT treatment in post-AMI patients.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Thrombosis; Vitamin K

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

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

Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT.. We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed.. Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.

Topics: Anticoagulants; Embolism; Hemorrhage; Humans; Stroke; Thrombosis; 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

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

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

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) 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

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

Current guidelines recommend vitamin K antagonists (VKAs) for left ventricular thrombus (LVT) resolution. Direct oral anticoagulants (DOACs) are increasingly evaluated as alternatives to the standard of care in anticoagulation.. We performed a systematic review and meta-analysis to assess the use of DOACs vs VKAs for LVT treatment. The occurrence of LVT resolution, systemic embolism (SE) or stroke, and bleeding events were compared during follow-up using random-effects analysis.. The 5 included studies were all observational (a total of 828 patients). Of these, 284 patients (34%) were treated with DOACs, and 544 (66%) treated with VKAs. Thrombus resolution was similar for both methods (pooled odds ratio [OR], 0.91; 95% CI, 0.47-1.75;. Our systematic review and meta-analysis suggests DOACs were as effective as VKAs for LVT resolution, with a similar risk of systemic embolism/stroke and clinically relevant bleeding. These results, obtained from observational studies, are not definitive and hence randomized controlled trials are needed. Nevertheless, our analysis identifies key experimental features required in future studies.

Topics: Administration, Oral; Age Factors; Anticoagulants; Diabetes Mellitus; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Hypertension; Platelet Aggregation Inhibitors; Sex Factors; Stroke; Thrombosis; 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

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

To determine the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) initiated early after cardiac surgery.. Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE (database inception to January 20, 2021), www.clinicaltrials.gov, www.who.int/ictrp/search/en/, NOAC trial registries, and bibliographies of relevant guidelines and other reviews were used.. Observational studies and randomized controlled trials (RCTs) that initiated NOACs within the index hospitalization and that reported bleeding for the primary outcome were included.. A total of 6 cohort studies, 1 RCT, and 3 ongoing RCTs were included. Most studies were single-centered, limited to postoperative atrial fibrillation after coronary artery bypass grafting, and with 30-day follow-up; few studies included patients with isolated bioprosthetic valve replacement or valve repair. Bleeding risk varied (0%-28.6%), and all but one study showed no significantly higher risk with NOAC compared with warfarin.. Overall, NOACs were used in 26% to 37.5% of patients early after cardiac surgery. Starting a NOAC on postoperative day 4 appeared to have similar bleeding rates compared with warfarin, but clinical application is limited by heterogeneity of outcome definitions, confounding, and bias. Compared with warfarin, NOACs may have similar thromboembolism risk, reduced length of stay, and cost.. There is limited evidence to guide NOAC use early after cardiac surgery. Three ongoing randomized trials will add to the literature and provide guidance for clinicians on whether, in whom, when, and how to use NOACs safely early after cardiac surgery.

Topics: Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Humans; Stroke; 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

Although several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus (LVT), those meta-analyses included no single-arm studies.. PubMed, Scopus, and the Cochrane Library databases were searched for articles investigating thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, or all-cause death in LVT treated with VKAs or DOACs, and single-class meta-analyses were also included (PROSPERO database, CRD42021230849). Event rates were pooled using a random effects model. Meta-regression analysis was performed to explore factors that may influence outcomes. 2,612 patients from 23 articles were included (VKAs: 2,004, DOACs: 608). There were no significant differences between VKAs and DOACs in the frequency of thrombus resolution (VKAs: 0.75 [95% confidence interval; 0.67 to 0.81], DOACs: 0.75 [0.67 to 0.82]), stroke (VKAs: 0.06 [0.04 to 0.10], DOACs: 0.02 [0.01 to 0.01]), any thromboembolism (VKAs: 0.08 [0.05 to 0.13], DOACs: 0.03 [0.01 to 0.10]), major bleeding (VKAs: 0.06 [0.04 to 0.09], DOACs: 0.03 [0.01 to 0.06]), any bleeding (VKAs: 0.08 [0.05 to 0.12], DOACs: 0.08 [0.06 to 0.10]), and all-cause death (VKAs: 0.07 [0.04 to 0.13], DOACs: 0.09 [0.05 to 0.16]). Meta-regression analysis revealed that increased duration of follow-up was associated with lower-rates of stroke (estimate: -0.040, p = 0.0495) with VKAs, but not with DOACs. There was significant publication bias for thrombus resolution, stroke, any thromboembolism, any bleeding, and all-cause death.. Efficacy and adverse outcomes of therapy with DOACs and VKAs do not differ. Randomized controlled trials are needed to determine the optimal anticoagulant strategy.

Topics: Administration, Oral; Anticoagulants; Heart Ventricles; Hemorrhage; Humans; International Normalized Ratio; Stroke; Thromboembolism; Thrombosis; 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

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 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

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

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

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

Transcatheter aortic valve implantation (TAVI) has been a favored option for the patient who suffered from symptomatic aortic stenosis. However, the efficacy and safety outcomes in novel oral anticoagulants (NOACs) versus Vitamin-K antagonist (VKA) for post-TAVI patients are still controversial. This meta-analysis aims at comparing the clinical outcome and safety of NOACs and VKA in the patients after receiving TAVI.. We searched literature articles in all reachable databases, and observational study as well as randomized controlled trial would be included in order to perform a comprehensive analysis. All-cause mortality, major or life-threatening bleeding, disabling or nondisabling stroke were main pooled outcome measures. Subgroup analysis and meta-regression were adopted to explore heterogeneity. Assessment of bias was performed under the suggestion of Cochrane's Collaboration Tool.. With corroborative analysis of severe complications, VKA is shown to be more protective on post-TAVI patients in disabling or nondisabling stroke scenario but not in mortality or bleeding event.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve Stenosis; Female; Hemorrhage; Humans; Male; Risk Assessment; Risk Factors; Stroke; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome; 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

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

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 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

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

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

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

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

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

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

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

Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only. For the factor Xa inhibitors, an antidote is being investigated in clinical trials. To our best knowledge, there are no direct head-to-head studies between the NOACs. Therefore, none of them can be assumed to be superior and the decision for a specific NOAC should be based on the available scientific data from the NOAC trials considering the individual patient's characteristics and comorbidities.. Zur Prophylaxe des kardioembolischen Schlaganfalls stehen neben Vitamin K-Antagonisten in Deutschland seit 2011 die sogenannten neuen oralen Antikoagulantien (NOAK) zur Verfügung. Eine Zulassung besteht für nicht-valvuläres Vorhofflimmern. Obwohl in Deutschland eine intensive Kontroverse zu diesem Thema geführt wird, wird das Nutzen-Risiko-Verhältnis der NOAK im Vergleich zu Vitamin K-Antagonisten von den neurologischen und kardiologischen Fachgesellschaften als günstiger bewertet. Dieser Effekt wird insbesondere durch die Risikoreduktion für intrazerebrale Blutungen vermittelt. Ein spezifisches Antidot steht für Dabigatran zur Verfügung und ist für die Faktor Xa-Inhibitoren in der klinischen Prüfung. Aus Mangel an direkten Vergleichsstudien kann keines der NOAK dem anderen als überlegen angesehen werden. Die Auswahl eines NOAK sollte sich daher unter Berücksichtigung der Ergebnisse der Zulassungsstudien an praktischen Aspekten und Komorbiditäten des einzelnen Patienten orientieren.

Topics: Anticoagulants; Antidotes; Fibrinolytic Agents; Humans; Stroke; 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

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

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

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

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

Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed.

Topics: Brain Ischemia; Female; Hemorrhage; Hemostasis; Humans; Infant, Newborn; Infant, Premature; Male; Stroke; Thrombosis; Vitamin K; von Willebrand Factor

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

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

In daily practice, chemical substances called "direct oral anticoagulants" or DOACs are more convenient to administer when set beside vitamin K antagonists (VKA) due to improved pharmacologic properties, fewer drug interactions and rapid onset of action. The objective of this review was to assess whether DOACs are the alternative for VKA in subjects with mild-to-moderate chronic kidney disease (CKD). An analysis of current DOAC trials and studies was performed focusing on subjects with CKD. This review concludes that although DOACS are not recommended in the course of advanced chronic kidney disease (CrCl<30mL/min) or during dialysis, DOACS are a reasonable choice for individuals with mild to moderate CKD.

Topics: Anticoagulants; Hemorrhage; Humans; Renal Insufficiency, Chronic; Stroke; Venous Thrombosis; 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

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

Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

Topics: Anticoagulants; Antidotes; Coronary Artery Disease; Drug Discovery; Factor XI; Factor XII; Heart Failure; Heparin; Humans; Peripheral Arterial Disease; Stroke; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

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

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

An 80-year-old man presents with an acute right hemiparesis and National Institutes of Health Stroke Scale (NIHSS) of 25, 14 h after taking dabigatran. Activated partial thromboplastin time (aPTT) is 42.8 s. Arteriogram demonstrates left internal carotid artery thrombosis. What is the appropriate management of this patient with acute ischemic stroke while on a NOAC?. Idarucizumab is a reversal agent approved for dabigatran, and two more reversal agents, andexanet alfa and aripazine, are currently in development for NOACs. In this article, we review currently available NOACs, their laboratory monitoring, and reversal agents.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Dabigatran; Factor Xa; Hemorrhage; Humans; Recombinant Proteins; Stroke; Thrombolytic Therapy; 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

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

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

The non-vitamin K antagonists (NOAC) are an integral component of our antithrombotic prevention and therapy. For four of the NOAC, their non-inferiority or even superiority versus vitamin K antagonists (VKA) has been proven. Thus, the management of special patient cohorts or the management of active bleeding complications is a focus of current discussion.In addition to prospective trials, numerous retrospective analyses of health insurers or public health provider data have been analyzed and published as "real life" or "real-world evidence" data. In almost all data sets the results of the NOAC approval trials were confirmed, demonstrating their non-inferiority or even superiority versus VKA. Attempts to compare the various NOAC with each other must be viewed critically since the real-world evidence (RWE) analysis provides very divergent results depending on the cohorts analyzed. Thus, a substantial prescriber-bias must be taken into account and never be excluded.In order to improve the management of bleeding complications, NOAC antidotes were developed. While the factors Xa antidote, andexanet alpha, a modified coagulation factor deleted of an intrinsic activity, will not be available before 2018, the dabigatran antidote idarucizumab is already in clinical use. Idarucizumab, a monoclonal antibody fragment directed against dabigatran, is able to completely antagonize the effect of dabigatran within minutes. Therefore, the drug has the potential to terminate life-threatening bleeding complications earlier and make emergency surgical or interventional procedures possible without an elevated bleeding risk.

Topics: Aged; Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Dabigatran; Factor Xa; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin

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

Over the past several years, non-vitamin K oral anticoagulants (NOACs) have been introduced into clinical practice for the treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Clinical trials have shown these agents to have similar or less risk of major bleeding as compared to warfarin therapy. Moreover, when patients do experience a major bleeding event administration of advanced factor products is rare, and post-bleed outcomes are similar in those receiving a NOAC compared to those receiving warfarin. However, there are situations where urgent reversal of NOAC anticoagulation would be desirable. The following review focuses on the outcomes and management strategies for patients experiencing a major bleed with warfarin or NOAC agents and describes the rationale for the development of therapies capable of targeted NOAC-reversal.

Topics: Administration, Oral; Animals; Anticoagulants; Antidotes; Hemorrhage; Humans; Stroke; Venous Thromboembolism; 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

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

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

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

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

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 (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

Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs.

Topics: Administration, Oral; Anticoagulants; Embolism; Humans; 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

Non-vitamin K antagonist oral anticoagulant (NOAC) drugs are at least equivalent to warfarin for ischemic stroke prevention in patients with atrial fibrillation and have a lower risk of intracranial hemorrhage. The role of these agents in the prevention and treatment of other types of cerebrovascular disease remains unclear.. We reviewed the literature (randomized trials, exploratory comparative studies, and case series) on the use of NOACs in patients with atrial fibrillation, venous thromboembolism, and cerebrovascular disease independent of atrial fibrillation.. The literature on the use of NOACs for treatment and prevention of cerebrovascular disease in patients without atrial fibrillation is sparse. The potential benefit of vitamin K antagonists over antiplatelet agents for primary and secondary prevention in certain subsets of patients with cerebrovascular disease is offset by the increased risk of major and intracranial hemorrhage. Given that NOACs are equivalent to vitamin K antagonists in preventing ischemic stroke and systemic embolism in patients with atrial fibrillation with less bleeding risk, clinical trials are needed to investigate the short- and long-term use of NOACs in populations of patients with other forms of cerebrovascular disease, including those with cryptogenic stroke with or without evidence of patent foramen ovale and low ejection fraction, cervical artery dissection, large artery atherosclerosis, venous thrombosis, and stuttering lacunar stroke.. There may be a role for NOACs in stroke prevention and treatment beyond atrial fibrillation. Randomized controlled trials are needed to compare NOACs to current stroke prevention and treatment strategies in certain subgroups of patients with cerebrovascular disease.

Topics: Administration, Oral; Anticoagulants; Humans; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; 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

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

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

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

In recent years, four nonvitamin K antagonist oral anticoagulants (NOACs) were approved to prevent stroke in patients with nonvalvular atrial fibrillation (AF) and to treat venous thromboembolism (VTE). Edoxaban, a direct factor Xa inhibitor, is the latest NOAC to be approved for use by the U.S. Food and Drug Administration. The other NOACs include two direct factor Xa inhibitors, apixaban and rivaroxaban, and one direct thrombin inhibitor, dabigatran. The purpose of this article is to introduce these agents to providers, discuss dosing, and offer insights into practical considerations for each NOAC.. PubMed was searched to identify randomized controlled trials and cost-effectiveness analyses evaluating NOACs. In addition, package inserts for the four NOACs provided pharmacologic data.. All four NOACs are equivalent to or better than warfarin for the treatment of VTE and stroke prevention in AF, and may reduce the risk of bleeding complications, particularly intracranial bleeding.. NOACs may benefit some patients by avoiding the numerous food or drug interactions and frequent laboratory monitoring associated with warfarin. Adherence to proper dosing is critical for NOAC efficacy and safety.

Topics: Administration, Oral; Anticoagulants; Humans; Randomized Controlled Trials as Topic; Stroke; United States; United States Food and Drug Administration; Venous Thromboembolism; Vitamin K

Anticoagulation for the prevention of stroke is an important aspect of the management of atrial fibrillation. Novel anticoagulants including oral factor Xa inhibitors rivaroxaban and apixaban and the direct thrombin inhibitor dabigatran have emerged as important therapeutic treatment options for prevention of stroke in non-valvular atrial fibrillation. These agents offer practical advantages over traditional vitamin K antagonists, however an understanding of their individual pharmacokinetic and other agent-specific differences is essential for identifying appropriate candidates for therapy, and for selecting the appropriate agent that will be effective and safe. Here, we review the pharmacokinetic process of oral medication use, summarize the newer anticoagulants, their pharmacology, individual pharmacokinetic features, and explore possible explanations for the differences in bleeding outcomes observed in the clinical trials.

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

Many cardiac patients require combined antithrombotic therapy consisting of an anticoagulant and inhibition of platelet function. The most frequent indications are atrial fibrillation (AF) in combination with drug-eluting stent implantation and/or the presence of an acute coronary syndrome (ACS). Currently, the optimal combination of anticoagulants and anti-platelet therapy is unknown, but it is well established that the combination of regular doses and regimens as prescribed in AF or after ACS results in increased bleeding rates. In this review, we discuss the current literature and describe approaches to reduce the risk of bleeding hoping not to increase the rate of ischaemic events.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Embolism; Fibrinolytic Agents; Graft Occlusion, Vascular; Hemorrhage; Humans; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Precision Medicine; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stroke; 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

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

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

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

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

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

Oral vitamin K antagonists are highly efficacious in the prevention and treatment of thromboembolic disease. Optimal use of these agents in clinical practice is challenged by their narrow therapeutic window. The proportion of time spent in the International Normalized Ratio (INR) range of 2.0-3.0 [time in the therapeutic range (TTR)] has been closely associated with adverse outcomes, i.e., stroke, hemorrhage, mortality. Although TTR is a validated marker, it has several limitations. TTR does not capture short-term risks associated with highly variable periods or periods characterized by extreme deviations in INR. Because TTR measurement is limited to consecutive periods of warfarin exposure, it does not inform the risks associated with gap periods of 56 days or greater as these time intervals are excluded from end-point rate calculations. Because individuals with gaps in monitoring represent a different patient population than those without gaps, e.g., less adherent, more acutely ill, more frequent transitions in health status, TTR analyses are likely most valid and informative for individuals with uninterrupted monitoring of the INR. Duration of warfarin therapy and patient-specific factors have also been shown to influence TTR. Younger age, female sex, lower income, black race, frequent hospitalizations, polypharmacy, active cancer, decompensated heart failure, substance abuse, psychiatric disorders, dementia, and chronic liver disease have all been associated with lower TTR. Targeted strategies to improve TTR are urgently needed.

Topics: Age Factors; Anticoagulants; Chronic Disease; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Liver Diseases; Male; Neoplasms; Sex Factors; Stroke; Substance-Related Disorders; Thromboembolism; Vitamin K; Warfarin

The field of thromboembolic disease and anticoagulation has had critical advances since the Anticoagulation Forum last met (May of 2011). We summarize our "top ten list" of papers that are likely to change the care of the anticoagulated population and improve their outcomes: (1) Patient self-management of their vitamin K antagonist and self monitoring can decrease thromboembolic events; (2) restarting warfarin after gastrointestinal bleeding may decrease mortality; (3) rivaroxaban is effective in the treatment of pulmonary embolism; either (4) apixaban or (5) low-dose aspirin prevented recurrent venous thromboembolic disease after a standard course of therapy; (6) warfarin prevents thrombotic complications up to at least 90 days after bioprosthetic aortic valve replacement; (7) the relative risk reduction of apixaban compared to warfarin is similar across CHADS2 scores, but the absolute risk reduction is higher in high-risk patients; (8) adherence to a warfarin dose-adjustment algorithm improved time in the therapeutic range and thromboembolic outcomes in the RE-LY trial; (9) warfarin had little benefit (if any) over aspirin in patients with decreased ejection fraction and sinus rhythm; (10) adding clopidogrel to aspirin in patients with lacunar infarcts did not reduce the risk of recurrent stroke and increased bleeding.

Topics: Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; Male; Risk Factors; Stroke; Thromboembolism; 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

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

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

Treatment with vitamin K antagonists are subject to a common iatrogenic mainly characterized by hemorrhagic stroke. Their narrow therapeutic range associated with variability largely explains this phenomenon. New oral anticoagulants (NOAC) are now available. dabigatran (Pradaxa®) is a direct and specific thrombin inhibitor. It is excreted mainly by the kidney and is the only which can be dialyzed. Rivaroxaban (Xarelto®) and apixaban (Eliquis®) are factor X activated direct inhibitors. They are highly bound to plasma proteins and are metabolized mainly by the liver, via CYP3A4. All NOAC are substrates of P-glycoprotein (P-gp). Due to pharmacological changes, some populations at risk were identified: patients with hepatic impairment, renal impairment, elderly patients or low weight. Some pharmacokinetic or pharmacodynamic drug interactions alter the concentration and the expected impact of NOAC. The NOAC does not require biological monitoring. They interfere with the routine coagulation tests which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Currently, no antidote is available. The new oral anticoagulant look promising in the elderly. However, certain rules must be followed to reduce the risk of iatrogenic.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Dose-Response Relationship, Drug; Drug Interactions; Drugs, Investigational; Humans; Iatrogenic Disease; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridones; 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

Among the different subtypes of ischaemic strokes, almost 20 % are of cardiac origin. Different are the causes of cardioembolic stroke, but the most common is the atrial fibrillation, a supraventricular arrhythmia. Appropriate use of antiplatelet drugs and anticoagulants after transient ischaemic attack (TIA) or ischaemic stroke depends on whether the underlying cause is cardioembolic or of presumed arterial origin. Adequate antiplatelet therapy is recommended for secondary prevention after cerebral ischaemia of presumed arterial origin, whether for patients with TIA and ischaemic stroke of cardiac origin, mainly due to atrial fibrillation. Vitamin K antagonists (VKAs) are highly effective in preventing recurrent ischaemic stroke but have important limitations and are thus underused. Current guidelines still regard Vitamin K Antagonists at INR 2·0-3·0 to be the standard treatment after cerebral ischaemia of cardiac origin for patients who can tolerate them. In this setting antiplatelet therapy provides an alternative when oral anticoagulation is contraindicated or when patient choice or compliance limits choice of therapy, but is much less effective than VKAs. Recent trial data performed with new anticogulants such as the factor Xa and thrombin inhibitors will need to be taken into account, in order to prevent several of the clinical problems actually related to VKAs use.

Topics: Animals; Anticoagulants; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Vitamin K

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

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

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 (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

Dabigatran etexilate is emerging as an alternative for vitamin K antagonists, but evidence-based guidelines for management of intracerebral hemorrhage and acute ischemic stroke in patients taking this drug are nonexistent. This review summarizes current knowledge on key pharmacological features and the assessment of dabigatran activity. Pragmatic approaches are provided for individualized decision taking with regard to hemostatic therapy and reperfusion strategies in acute stroke patients.

Topics: Anticoagulants; Benzimidazoles; Blood Coagulation Disorders; Case Management; Cerebral Hemorrhage; Cerebral Infarction; Dabigatran; Guidelines as Topic; Hemostasis; Hemostatics; Humans; Off-Label Use; Pyridines; Renal Dialysis; Reperfusion; Stroke; 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

The vitamin K antagonists (VKA) available for stroke prevention in patients with atrial fibrillation have many drawbacks due to their difficult clinical use and high risk of bleeding. Currently, several drugs are being developed as possible substitutes for VKA that have many advantages such as the lack of monitoring requirement and scarce pharmacologic and food interactions. The present article provides an update on the new oral anticoagulants that are in a more advanced stage of clinical research, their pharmacologic properties, advantages and disadvantages and their results in recent clinical trials.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Monitoring; Drugs, Investigational; Hemorrhage; Humans; Morpholines; Multicenter Studies as Topic; Patient Care Planning; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; 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

People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with vitamin K antagonists is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy.. To compare the efficacy and safety of vitamin K antagonists and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin.. We searched the Cochrane Stroke Group Trials Register (last searched 15 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September 2011) and EMBASE (2008 to September 2011). In an effort to identify further relevant trials we searched ongoing trials registers and reference lists. We also contacted authors of published trials for further information and unpublished data.. Randomised trials of oral anticoagulant therapy with vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus antiplatelet therapy for long-term secondary prevention after recent transient ischaemic attack or minor ischaemic stroke of presumed arterial origin.. Two review authors independently selected trials, assessed trial quality and extracted data.. We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21).. For the secondary prevention of further vascular events after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications.

Topics: Administration, Oral; Anticoagulants; Cause of Death; Hemorrhage; Humans; International Normalized Ratio; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; 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

Ischemic stroke is the third most common cause of death and of long-term disability and exhibits a high recurrence rate. Therefore, appropriate primary and secondary prevention is mandatory. In non-cardioembolic stroke, in addition to lifestyle changes and to targeted treatments, current guidelines recommend antiplatelet treatment. In cardioembolic stroke, Vitamin K antagonists (VKAs) are recommended. Although a favorable risk/benefit ratio of both treatments has also been demonstrated in elderly patients, registry data emphasize that such interventions are often under-used, especially in patients with atrial fibrillation (AF). Furthermore, variability in the inter-individual response to drugs has been recognized as a leading cause of event recurrence. Thus, in addition to poor adherence, efficacy and safety issues appear to be involved in the recurrence rate of stroke. In this review, we report main Registries data on adherence to stroke prevention treatment schedule. We also discuss the major limitations of "traditional" antithrombotic drugs and report Phase III study results on safety and efficacy of new antiplatelet and anticoagulant drugs, with emphasis on stroke prevention.

Topics: Aged; Anticoagulants; Fibrinolytic Agents; Humans; Medication Adherence; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Primary Prevention; Secondary Prevention; Stroke; Vitamin K

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

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

Oral anticoagulant-associated intracerebral hemorrhage is increasing in incidence and is the most feared complication of therapy with vitamin K1 antagonists. Anticoagulant-associated intracerebral hemorrhage has a high risk of ongoing bleeding, death, or disability. The most important aspect of clinical management of anticoagulant-associated intracerebral hemorrhage is represented by urgent reversal of coagulopathy, decreasing as quickly as possible the international normalized ratio to values ≤1·4, preferably ≤1·2, together with life support and surgical therapy, when indicated. Protocols for anticoagulant-associated intracerebral hemorrhage emphasize the immediate discontinuation of anticoagulant medication and the immediate intravenous administration of vitamin K1 (mean dose: 10-20 mg), and the use of prothrombin complex concentrates (variable doses calculated estimate circulating functional prothrombin complex) or fresh-frozen plasma (15-30 ml/kg) or recombinant activated factor VII (15-120 μg/kg). Because of cost and availability, there is limited randomized evidence comparing different reversal strategies that support a specific treatment regimen. In this paper, we emphasize the growing importance of anticoagulant-associated intracerebral hemorrhage and describe options for acute coagulopathy reversal in this setting. Additionally, emphasis is placed on understanding current consensus-based guidelines for coagulopathy reversal and the challenges of determining best evidence for these treatments. On the basis of the available knowledge, inappropriate adherence to current consensus-based guidelines for coagulopathy reversal may expose the physician to medico-legal implications.

Topics: Administration, Oral; Algorithms; Anticoagulants; Cerebral Hemorrhage; Factor VIIa; Guidelines as Topic; Humans; Neurosurgical Procedures; Plasma; Prothrombin; Risk Assessment; Stroke; Vitamin K

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

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

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

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

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

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

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

There is little consensus on the optimal perioperative management for most patients on oral anticoagulation with vitamin K antagonists. Bridging therapy is not recommended for the majority of patients on oral anticoagulation as most are at low risk for perioperative stroke. Though most clinicians choose an aggressive perioperative strategy for patients with high thromboembolic risk (e.g., mechanical mitral valve replacement) by withholding warfarin perioperatively and the use of full-dose heparin, prophylactic dose heparin is given for lower risk cagegories (e.g., bileaflet aortic valve replacement and atrial fibrillation). The amount of increase in postoperative major bleeding when full-dose anticoagulation is administered soon after surgery is the factor in the decision with the least available data. The optimal method for returning the International Normalized Ratio (INR) to the desired range preoperatively depends upon its degree of initial elevation and whether or not clinically significant bleeding is present. Rapid reversal of excessive anticoagulation should be undertaken in patients with serious bleeding at any degree of anticoagulation. Vitamin K therapy is an effective treatment for INR prolongation in patients with vitamin K-associated coagulopathy; coagulation factor replacement is required, in addition, in patients with major bleeding or with an indication for immediate correction of their INR. Patients receiving prothrombin complex concentrate have a more rapid and more complete reversal of their anticoagulation as compared with fresh frozen plasma.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Factors; Cohort Studies; Coumarins; Hemorrhage; Heparin; Humans; International Normalized Ratio; Perioperative Care; Plasma; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Stroke; Thromboembolism; Vitamin K; Warfarin

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

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

Recombinant factor VIIa has been increasingly used to provide hemostasis in nonapproved indications. This trend has resulted in concerns about safety, efficacy and costs.. Recombinant factor VIIa seems to have hemostatic effects in posttrauma and perisurgery excessive bleeding, although further studies are required. Recombinant factor VIIa may be used to reverse the effect of warfarin or other vitamin K-antagonist therapy following vitamin K administration. Some beneficial effects have also been suggested in a limited number of patients with liver disease and hemorrhagic stroke. Recombinant factor VIIa should be used with caution in cases with known hypercoagulability, excessive bleeding in the setting of disseminated intravascular coagulation or other states of generalized activation of the hemostatic system. In most of the nonapproved cases, a 4.8-mg vial administered to an adult patient weighing 50-100 kg to achieve a 50-100 microg/kg dose is recommended.. While consensus recommendations on the use of recombinant factor VIIa in nonapproved settings have been developed, more studies are needed to define dose and timing in these diverse patient populations. For now, decisions about off-label use of recombinant factor VIIa remain at the physician's discretion, assisted by hospital pharmacotherapeutic or transfusion committees.

Topics: Adult; Consensus; Disseminated Intravascular Coagulation; Drug Antagonism; Drug-Related Side Effects and Adverse Reactions; Factor VIIa; Hemostasis; Hospitals; Humans; Pharmacy and Therapeutics Committee; Recombinant Proteins; Stroke; Vitamin K; Warfarin

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

Topics: Adult; Aged; Anticoagulants; Factor VII; Factor VIIa; Female; Hematoma, Subdural; Humans; Intracranial Hemorrhages; Israel; Male; Middle Aged; Recombinant Proteins; Stroke; 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

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Humans; Prodrugs; Stroke; Venous Thrombosis; 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

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

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

Thrombin has long been a target for development of oral anticoagulants but it has been difficult to find synthetic inhibitors with a desirable combination of pharmacodynamic and pharmacokinetic properties. However, there are now two oral direct thrombin inhibitors (DTIs) in clinical development, ximelagatran (ExantaTM) and BIBR 1048. Both are prodrugs with two protecting groups that are eliminated after absorption from the gastrointestinal tract. Their main active substances, melagatran and BIBR 953, are both potent and selective DTIs. In experimental models of thrombosis, melagatran has been shown to have a shallower dose-response curve than warfarin and, therefore, a better separation between efficacy and bleeding. Oral bioavailability, measured as the plasma concentration of the active metabolite, seems to be higher for ximelagatran (20%) than for BIBR 1048 (estimated to 5%). BIBR 953 has a longer half-life (about 12 h) than does melagatran (3-5 h) after oral administration of BIBR 1048 and ximelagatran, respectively. Both melagatran and BIBR 953 are mainly eliminated via the renal route. The variability of the plasma concentration of melagatran after oral administration of ximelagatran is low. There are no clinically relevant interactions with food or cytochrome P450 metabolized drugs and ximelagatran. In clinical studies, ximelagatran has been administered in a twice-daily fixed-dose regimen without coagulation monitoring. Results of published clinical studies are encouraging, both with regard to efficacy and bleeding. Major indications in Phase III studies with ximelagatran are the prevention of venous thromboembolism (VTE) in hip and knee replacement surgery, treatment and long-term secondary prevention of VTE and prevention of stroke in patients with nonvalvular atrial fibrillation. It is anticipated that with a favourable outcome of the Phase III clinical studies new oral DTIs, with the oral fixed-dose regimen without routine coagulation monitoring, will ease the use of today's anticoagulant therapy.

Topics: Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Glycine; Hemostasis; Humans; Prodrugs; Pyridines; Stroke; Thrombin; Thrombosis; Venous Thrombosis; Vitamin K

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

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

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

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

Mechanical thrombectomy (MT) is one of the main treatments for acute ischemic stroke (AIS) in patients on effective anticoagulation. The use of direct oral anticoagulants (DOA) has increased, given their efficacy and safety profile compared to vitamin K antagonists (VKA). We compared procedural and clinical outcomes of MT in patients on DOA and VKA treatment before stroke onset. We analyzed 2 groups from the Endovascular Treatment in Ischemic Stroke prospective registry: patients on DOA and patients on VKA treated by MT without thrombolysis. Generalized linear mixed models including center as random effect were used to compare angiographic (rates of reperfusion at end of procedure, number of passes >2, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to anticoagulation subgroups. Comparisons were adjusted for prespecified confounders (age, admission NIH Stroke Scale score) as well as for meaningful baseline between-group differences. Among 221 patients included, more DOA-treated patients (n = 115, 52%) achieved successful (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b/3) or near complete (mTICI 2c/3) reperfusion at the procedure end than did VKA-treated patients, with an adjusted odds ratio (OR) for DOA vs VKA of 3.27 (95% confidence interval [CI], 1.40-7.65) and 2.00 (95% CI, 1.08-3.73), respectively. DOA-treated patients had a lower 90-day mortality risk with an adjusted OR of 0.47 (95% CI, 0.24-0.89) and a better excellent outcome OR of 2.40 (1.10-5.27). There was no significant between-group difference in hemorrhagic or procedural complications. The study highlights the benefits of DOA compared to VKA. Regarding mortality, excellent outcomes, and recanalization rate, DOA appears to provide a favorable setting for MT treatment in AIS.

Topics: Aged; Anticoagulants; Dabigatran; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Registries; Reperfusion; Rivaroxaban; Stroke; Thrombectomy; Treatment Outcome; 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

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 potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.. To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.. 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).. 6 university hospitals in Spain.. 190 adults (aged 18 to 75 years) with thrombotic APS.. Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).. The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.. After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.. Anticoagulation intensity was not measured in the rivaroxaban group.. Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.. Bayer Hispania.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; 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

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

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

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

Intracerebral hemorrhage (ICH) is a life-threatening complication of non-vitamin K antagonist oral anticoagulants (NOAC). Little is known about the effect of intensity of anticoagulation on NOAC-ICH. We describe the current use of coagulation testing in the emergency setting and explore associations with baseline size and expansion of hematoma as determined in a previous study.. Data from the prospective multicenter RASUNOA registry were analyzed. Patients with NOAC-ICH were enrolled between February 2012 and December 2014. Frequency of local test performance of specific (anti-factor Xa tests, diluted thrombin time) and non-specific tests (international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time) was analyzed. The association of anticoagulation intensity at admission with hematoma volume and hematoma expansion was explored.. In 61 NOAC-ICH patients enrolled at 21 centers, drug-specific coagulation testing was performed in 16 cases (26%), and only 29% of centers appeared to use drug-specific tests in NOAC-ICH at all. In some cases, INR and aPTT values were normal despite drug concentrations in the peak range. In patients with available drug-specific concentrations, 50% had drug levels in the peak range at admission. Higher intensity of anticoagulation was not associated with higher hematoma volume at admission or with subsequent hematoma expansion.. Drug-specific tests are only infrequently used in NOAC-ICH. Normal results in non-specific coagulation do not reliably rule out peak range concentrations. Anticoagulation intensity at admission does not predict baseline hematoma volume or subsequent hematoma expansion.

Topics: Aged; Aged, 80 and over; Antithrombins; Blood Coagulation Tests; Cerebral Hemorrhage; Female; Humans; Male; Middle Aged; Registries; Stroke; Vitamin K

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

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

In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke.. Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored.. In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients.. NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Brain Ischemia; Female; Germany; Humans; Male; Prospective Studies; Registries; Stroke; 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

The coagulopathy of cirrhosis is complex, placing patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have equivalent or superior efficacy and safety as compared to vitamin K antagonists (VKAs); however, their efficacy and safety in liver cirrhosis has not been studied. To better define this, we evaluated outcomes of patients with cirrhosis prescribed DOACs compared to other anticoagulants at our center.. Retrospective cohort study of patients with cirrhosis prescribed therapeutic anticoagulation over a 3-year period for thrombosis or prevention of stroke in patients with atrial fibrillation. The primary outcomes of interest were bleeding events and recurrent thrombosis or stroke.. During the study period, 27 patients with cirrhosis were prescribed a DOAC and 18 were prescribed VKA or low molecular weight heparin (LMWH). Both groups had similar total bleeding events (8 DOAC vs 10 other, P=.12). There were significantly less major bleeding episodes in the DOAC group (1 [4%] vs 5 [28%], P=.03). Recurrent thrombosis occurred in one patient receiving a DOAC (4%) and one patient (6%) receiving other anticoagulation (P=1.0).. Direct oral anticoagulant use in patients with cirrhosis may be as safe as traditional anticoagulants. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or thrombosis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Stroke; Thrombosis; Vitamin K

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

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

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

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

In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants.. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed.. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867).. Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation.

Topics: Aged; Anticoagulants; Asia, Eastern; Asian People; Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Vitamin K; Warfarin

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

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

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

Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk in many clinical conditions. Genetic variants of vitamin K epoxide reductase (VKORC-1) are associated with increased VKA effect and bleeding risk. It is unknown whether these variants could also affect the long-term outcome in patients with high-dosage oral anticoagulation and/or more difficult adherence to the therapeutic INR range. Hundred and twenty-four patients with mechanical heart valve replacement assuming VKA were genotyped for VKORC-1 -1639G>A (Rs9923231) polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were retrospectively assessed for a 6-year period. Furthermore, stability of their INR in relationship with the VKORC-1 genotype was investigated day-by-day for 3 months. No differences were observed in hemorrhage and venous thrombosis events according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P = 0.0008). During the daily observation period, A allele carriers had lower VKA requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P = 0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG genotype, P = 0.036). Conversely, patients with GG genotype had a more stable dosage of VKA (P = 0.006) and a higher percentage of examinations under the therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P = 0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a different warfarin dosage, anticoagulation level, time spent outside the therapeutic range and, in the long-term, a different incidence of atherothrombotic events.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Follow-Up Studies; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mixed Function Oxygenases; Myocardial Infarction; Polymorphism, Genetic; Retrospective Studies; Stroke; Time Factors; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

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

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

gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K-dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G>A change leads to the substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.

Topics: Aged; Asian People; Calcium-Binding Proteins; Carbon-Carbon Ligases; Female; Genetics, Population; Humans; Japan; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Single Nucleotide; Protein C; Protein Processing, Post-Translational; Protein S; Stroke; Vitamin K; Vitamin K Epoxide Reductases

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Canada; Double-Blind Method; Hemorrhage; Humans; Risk; Stroke; Thrombin; Treatment Outcome; United States; 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

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

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

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

Meta-analysis may increase the risk of random errors. Trial sequential analysis (TSA) has been developed to adjust for these random errors. We conducted TSA on the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in left ventricular thrombus (LVT) patients in order to estimate how many additional patients should be required to draw definite conclusions. PubMed, Scopus, and Cochrane Library databases were searched for articles directly comparing DOACs and VKAs for LVT in LV thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, and all-cause death. TSA was conducted with a cumulative Z-curve, monitoring boundaries, and required sample size. A simulated trial was run and TSA estimated the sample sizes of trials needed to draw definite conclusions. Of 4749 articles, 25 studies were used for the analysis. TSA revealed the current sample size already demonstrated superiority of DOACs in LV thrombus resolution and stroke, and futility in any thromboembolism and all-cause death. Two other outcomes did not achieve the required sample size. The sample size of new trials needed to demonstrate the superiority of DOACs over VKAs was estimated 400 for any bleeding. Corresponding trials needed to demonstrate no significant differences could be estimated for major bleeding and any bleeding (n = 200 and n = 2000, respectively). Current results show that the sample size required to draw definite conclusions was not reached for two outcomes, and there was a risk of random error. Further randomized controlled trials with sample sizes estimated by TSA will work effectively to obtain valid conclusions.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Meta-Analysis as Topic; Stroke; Thromboembolism; Thrombosis; 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

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: Brain Ischemia; Endovascular Procedures; Humans; Intracranial Hemorrhages; Retrospective Studies; Stroke; Thrombectomy; Treatment Outcome; Vitamin K

Topics: Brain Ischemia; Endovascular Procedures; Humans; Intracranial Hemorrhages; Retrospective Studies; Stroke; Thrombectomy; Treatment Outcome; 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

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

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

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

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

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

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

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

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

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

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

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

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: 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

This study aimed to evaluate the cerebroprotective potential of a novel synthetic coumarin, (E)-4-amino-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene) benzohydrazide noted (HC) against a pharmaceutically induced ischemic stroke in experimental male

Topics: Animals; Brain Ischemia; Ischemic Stroke; Isoproterenol; Male; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Stroke; Vitamin K; Vitamins

This study determined the influence of age on bleeding characteristics and clinical outcomes in primary spontaneous (non-OAC), vitamin K antagonist-related (VKA-) and non-vitamin K antagonist oral anticoagulant-related (NOAC-) ICH.. Pooled individual patient data of multicenter cohort studies were analyzed by logistic regression modelling and propensity-score-matching (PSM) to explore the influence of advanced age on clinical outcomes among non-OAC-, VKA-, and NOAC-ICH. Primary outcome measure was functional outcome at three months assessed by the modified Rankin Scale, dichotomized into favorable (mRS = 0-3) and unfavorable (mRS = 4-6) functional outcome. Secondary outcome measures included mortality, hematoma characteristics, and frequency of invasive interventions.. In VKA-ICH 33.5% (670/2001), in NOAC-ICH 44.2% (69/156) and in non-OAC-ICH 25.2% (254/1009) of the patients were ≥80 years. After adjustment for treatment interventions and relevant parameters, elderly ICH patients comprised worse functional outcome at three months (adjusted odds ratio (aOR) in VKA-ICH: 1.49 (1.21-1.84); p < 0.001; NOAC-ICH: 2.01 (0.95-4.26); p = 0.069; non-OAC-ICH: 3.54 (2.50-5.03); p < 0.001). Anticoagulation was significantly associated with worse functional outcome below the age of 70 years, (aOR: 2.38 (1.78-3.16); p < 0.001), but not in patients of ≥70 years (aOR: 1.21 (0.89-1.65); p = 0.217). The differences in initial ICH volume and extent of ICH enlargement between OAC-ICH and non-OAC-ICH gradually decreased with increasing patient age.. As compared to elderly ICH-patients, in patients <70 years OAC-ICH showed worse clinical outcomes compared to non-OAC-ICH because of larger baseline ICH-volumes and extent of hematoma enlargement. Treatment strategies aiming at neutralizing altered coagulation should be aware of these findings.

Topics: Administration, Oral; Aged; Anticoagulants; Cerebral Hemorrhage; Hematoma; Humans; Stroke; 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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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; Aged; Anticoagulants; Atrial Fibrillation; Humans; Stroke; Vitamin K; Warfarin

The efficacy of direct oral anticoagulants (DOACs) in the management of left ventricular (LV) thrombi remains to be determined, especially in patients with ischemic cardiomyopathy. This retrospective study sought to compare the efficacy of vitamin K antagonists (VKAs) and DOACs in patients with LV thrombi and evaluate the rate of LV thrombus resolution after adjusting anticoagulation.. This observational retrospective study included patients admitted to our institution for LV thrombus between January 2010 and August 2019. The rate of LV thrombus resolution was compared between VKAs and DOACs. Patients without thrombus resolution with DOAC treatment were switched to VKA agents in order to obtain an international normalized ratio (INR) of 3-4.. Between January 2010 and August 2019, 59 consecutive patients with LV thrombi detected by transthoracic echocardiography were included in the study. The mean age was 62 ± 14 years and 16.9% were women. The circumstances of LV thrombus discovery were as follows: acute myocardial infarction or ischemic myocardiopathy (n = 22), stroke (n = 6), chest pain (n = 7), heart failure (n = 11), transthoracic echocardiographic evaluation (n = 11), and ventricular arrhythmias (n = 2). The proportion of patients on DOACs was 28.8% (n = 17), while that of those on VKAs was 71.2% (n = 42). Thrombus resolution was obtained in 70.6% (12/17) of patients on DOACs and in 71.4% (30/42) of those on VKAs (p = 0.9). Patients who failed to respond to DOAC treatment were treated with VKAs, and following this treatment adjustment all LV thrombi were dissolved in the DOAC group (5/5). Five embolic events (8.4% of stroke) occurred before the treatment initiation and six with anticoagulants (2/17 with DOACs [11.8%] and 4/42 with VKAs [9.5%]; p = 0.8).. This retrospective observational study found a similar efficacy between DOAC and VKA agents in patients with LV thrombi (70.6% vs. 71.5%); however, when the thrombus remains, VKAs are still the standard of care as it is possible to control INR levels (3-4) with them.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Arrhythmias, Cardiac; Female; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Stroke; Thrombosis; Vitamin K

Despite the utility of neuroimaging in the diagnostic and therapeutic management of patients with acute ischemic stroke (AIS), imaging characteristics in patients with preceding direct oral anticoagulants (DOAC) compared to vitamin K antagonists (VKA) have hardly been described. We aimed to determine presence of large vessel occlusion (LVO), thrombus length, infarction diameter, and occurrence of hemorrhagic transformation in AIS patients with preceding DOAC as compared to VKA therapy.. Using a prospectively collected cohort of AIS patients, we performed univariate and multivariable regression analyses regarding imaging outcomes. Additionally, we provide a sensitivity analysis for the subgroup of patients with confirmed therapeutic anticoagulation.. We included AIS in patients with preceding DOAC (N = 75) and VKA (N = 61) therapy, median age 79 (IQR 70-83), 39% female. Presence of any LVO between DOAC and VKA patients (29.3% versus 37.7%, P = 0.361), and target LVO for endovascular therapy (26.7% versus 27.9%, P = 1.0) was equal with a similar occlusion pattern. DOAC as compared to VKA were associated with a similar rate of target LVO for EVT (aOR 0.835, 95% CI 0.368-1.898). The presence of multiple lesions and characteristics of the thrombus were similar in DOAC and VKA patients. Acute ischemic lesion diameter in real world patients was equal in patients taking DOAC as compared to VKA. Lesion diameter in VKA patients (median 13 mm, IQR 6-26 versus median 20 mm, IQR 7-36, P = 0.001), but not DOAC patients was smaller in the setting of confirmed therapeutic VKA. The frequency of radiological hemorrhagic transformation and symptomatic intracranial hemorrhage in OAC patients was low. Sensitivity analysis considering only patients with confirmed therapeutic anticoagulation did not change any of the results.. Preceding DOAC treatment showed equal rates of LVO and infarct size as compared to VKA in AIS patients. This study adds to the knowledge of imaging findings in AIS patients with preceding anticoagulation.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Brain Ischemia; Cohort Studies; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Prospective Studies; Stroke; 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

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

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

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

 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

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

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

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

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

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

Previous research has identified a possible association between vitamin K intake and cardiometabolic disease. This could mean that the assessment of vitamin K intake is a meaningful tool when monitoring individuals with preexisting cardiovascular disease. Sixty chronic stroke survivors (men and women, body mass index (BMI) 30.36 ± 6.61 kg/m

Topics: Aged; Chronic Disease; Diet Records; Eating; Female; Food Analysis; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Nutritional Requirements; Recommended Dietary Allowances; Stroke; Vitamin K

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

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

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

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

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

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

Prior studies suggest an association between Vitamin K antagonists (VKA) and cerebral microbleeds (CMBs); less is known about nonvitamin K oral anticoagulants (NOACs). In this observational study we describe CMB profiles in a multicenter cohort of 89 anticoagulation-related intracerebral hemorrhage (ICH) patients. CMB prevalence was 51% (52% in VKA-ICH, 48% in NOAC-ICH). NOAC-ICH patients had lower median CMB count [2(IQR:1-3) vs. 7(4-11); P < 0.001]; ≥5 CMBs were less prevalent in NOAC-ICH (4% vs. 31%, P = 0.006). This inverse association between NOAC exposure and high CMB count persisted in multivariable logistic regression models adjusting for potential confounders (OR 0.10, 95%CI: 0.01-0.83; P = 0.034).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Cohort Studies; Female; Humans; Male; Middle Aged; Prevalence; Retrospective Studies; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Stroke; 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

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

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

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

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

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

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

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

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

Recent studies indicated that functional outcome after intracranial hemorrhage (ICH) related to direct oral anticoagulation (DOAC-ICH) is similar, if not better, than vitamin K antagonist (VKA)-related ICH (VKA-ICH) due to a smaller initial hematoma volume (HV). However, the association with hematoma expansion (HE) and location is not well understood.. We retrospectively analyzed 102 consecutive patients with acute non-traumatic ICH on oral anticoagulation therapy to determine HV and HE stratified by hematoma location, and the relation to the 90-day outcome.. DOAC-ICH (n = 25) and VKA-ICH (n = 77) had a similar admission HV and HE (unadjusted p > 0.05, each). Targeted reversal strategies were used in 93.5% of VKA-ICH versus 8% of DOAC-ICH. After adjustment, an unfavorable 90-day functional outcome (modified Rankin scale score 4-6) was independently associated with a lower admission Glasgow Coma Scale score (OR 1.63; 95% CI 1.26-2.10; p < 0.001) and greater HV (OR 1.03; 95% confidence interval (CI) 1.00-1.05; p = 0.046). After exclusion of patients without follow-up head computed tomography to allow for adjustment by occurrence of HE, VKA-ICH was associated with an approximately 3.5 times greater odds for a poor 90-day outcome (OR 3.64; 95% CI 1.01-13.09; p = 0.048). However, there was no significant association of the oral anticoagulant strategy with 90-day outcome in the entire cohort (OR 2.85; 95% CI 0.69-11.86; p = 0.15).. DOAC use did not relate to worse HE, HV, and functional outcome after ICH, adding to the notion that DOAC is a safe alternative to VKA even in the absence of access to targeted reversal strategies (which are still not universally available).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Female; Hematoma; Humans; Intracranial Hemorrhages; Male; Radiography; Retrospective Studies; 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

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

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

 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

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

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

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

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

Although direct oral anticoagulants (DOAC) have proven at least equally effective in the prevention of acute ischemic stroke (AIS) in patients with atrial fibrillation as compared to the vitamin K antagonists (VKA), no reliable data on the severity of AIS of DOAC patients as compared to VKA is available.. Using a prospectively collected cohort of AIS patients, we performed univariate and multivariate (displayed as adjusted Odds Ratios, OR and 95% confidence intervals, 95% CI) analyses regarding the severity of AIS in patients with preceding DOAC (N = 210) versus VKA (N = 173) therapy. Additionally, we provide a sensitivity analysis considering only patients with warranted therapeutic anticoagulation activity.. In a comprehensive stroke center population, the frequency of AIS under DOAC was multiple times higher than previously reported at around 6% of all AIS and steadily increasing. National Institute of Health Stroke Scale (NIHSS) in VKA patients (median 7, IQR 2-14) was equal to DOAC (median 5, IQR 2-16) on univariate analysis (P = 0.229). According to the multivariable linear logistic regression analysis adjusting for confounders of severe stroke, VKA was not significantly associated with higher NIHSS scores (β - 0.165, 95% CI - 1.874 to 1.545, P = 0.850) as compared to DOAC. Also in the sensitivity analysis considering only patients with warranted therapeutic OAC therapy, VKA was not significantly associated with higher NIHSS scores (β - 1.392, 95% CI - 3.506 to 0.721, P = 0.195) as compared to DOAC. However, VKA as compared to DOAC was significantly associated with lower rates of good functional outcome at three months (0.527, 95% CI 0.300-0.928), but not with increased mortality (aOR 1.825, 95% CI 0.780-4.273).. Ischemic stroke in patients taking DOAC is an important and frequent scenario. Stroke severity in our real world population dataset is equal in patients taking VKA and DOAC, also in the case of warranted anticoagulation therapy. Preceding VKA as compared to DOAC was associated with lower rates of good functional outcome without excess mortality, but a causal relationship cannot be proven by our study design.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; Male; Pre-Exposure Prophylaxis; Prospective Studies; Registries; Severity of Illness Index; Stroke; 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

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)-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

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

Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Topics: American Heart Association; Amyloid; Anticoagulants; Cerebral Small Vessel Diseases; Clinical Decision-Making; Expert Testimony; Humans; Intracranial Hemorrhages; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; United States; Vitamin K; Warfarin

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

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

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

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

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

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

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

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

The uninterrupted use of oral anticoagulation (OAC) with vitamin K antagonists (VKAs) for electrophysiology procedures has been more and more recommended. The clinical practice in our service recommends the continuous use of these drugs for atrial flutter ablation. There is little evidence as to the uninterrupted use of non-vitamin K antagonist oral anticoagulants (NOACs) in this scenario.. To compare the rates of complications related with the uninterrupted use of different types of oral anticoagulants in patients referred to atrial flutter (AFL) ablation.. Historical, single-center cohort of ablation procedures by AFL conducted from November 2012 to April 2016. The primary outcome was the occurrence of hemorrhagic or embolic complication during the procedure. The secondary outcome was the occurrence of stroke or transient ischemic attack (TIA) in follow-up. The statistical significance level was 5%.. There were 288 ablations per AFL; 154 were carried out with the uninterrupted use of OAC (57.8% with VKA and 42.2% with NOAC). Mean age was 57 ± 13 years. The rate of hemorrhagic complication during the procedure was 3% in each group (p = NS). The rate of stroke/TIA was, respectively, of 56/1,000 people-year in the VKA group against zero/1,000 people-year in the NOAC group (p = 0.02).. In our population there were no hemorrhagic complications regarding the procedure of OAC use uninterruptedly, including NOACs. There was higher occurrence of stroke/TIA in the follow-up of the group of patients undergoing VKAs; however, this difference may not only be a result of the type of OAC used.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Flutter; Catheter Ablation; Cohort Studies; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Risk Factors; Stroke; Venous Thromboembolism; 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

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Stroke; 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

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

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

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

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

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

Topics: Anticoagulants; Atrial Fibrillation; Emergency Medicine; Humans; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Emergency Medicine; Humans; Stroke; Vitamin K

Antithrombotic treatment plays a key role in stroke prevention, but their direct effects on the composition of carotid artery atherosclerotic plaques are unknown. To investigate the association of antithrombotic treatment with carotid artery plaque composition, with a specific focus on an intraplaque haemorrhage (IPH).. From the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis on ultrasound (mean age 72.9 years, 46.0 women) underwent magnetic resonance imaging of the carotid arteries to assess plaque composition. Information on the use of oral anticoagulants [vitamin K antagonists (VKA)] and antiplatelet agents (salicylates), including duration of use and dosage, was obtained from pharmacy records for all participants. We used logistic regression models to assess the association between the use of anticoagulants and antiplatelet agents, and the different plaque components adjusting for confounders. Current and past use of VKA [adjusted odds ratio (OR): 1.88, 95% confidence interval (CI): 0.74-4.75 and OR 1.89, 95% CI: 0.91-3.93] and antiplatelet agents (OR: 1.22, 95% CI: 0.91-1.62), and (OR: 1.23, 95% CI: 0.86-1.75) showed positive trend with a higher presence of IPH. Also, a longer duration of use was associated with a higher frequency of IPH (OR: 3.15, 95% CI: 1.23-8.05) for the use of VKA, and longer duration of the use for antiplatelet agents showed a positive trend (OR: 1.21, 95% CI: 0.88-1.67). We also found that higher levels of international normalized ratio above 2.97 for VKA (OR: 1.48, 95% CI: 1.03-2.15) and higher daily defined dosage than 1.0 for antiplatelet agents (OR: 1.50, 95% CI: 1.21-1.87) were related to a higher frequency of IPH. We found no association with lipid core or calcification.. The use of antithrombotic treatment relates to a higher frequency of IPH in carotid atherosclerotic plaques.

Topics: Aged; Anticoagulants; Carotid Artery Diseases; Cross-Sectional Studies; Drug Administration Schedule; Female; Fibrinolytic Agents; Hemorrhage; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Stroke; 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

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

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

Intracranial haemorrhages (ICH) represent a severe and frequently lethal complication in patients treated with vitamin K antagonists (VKA). The purpose of our study is to describe the factors and clinical features associated with mortality in these patients.. We conducted an observational, retrospective, multi-centre study based on prospective stroke registries in Spain. We included all patients admitted to neurology departments during a one-year period who met the following inclusion criteria: being 18 or older, having a diagnosis of ICH, and receiving VKA. Clinical and radiological parameters and 3-month outcomes were analysed.. A total of 235 patients from 21 hospitals were included. Mortality rate at 90 days was 42.6%. Bivariate analysis showed a significant association between death and the following factors: median NIHSS score at admission (5 [IQR = 9] vs 17 [IQR = 14] points, P<.01) and presence of an extensive hemispheric haemorrhage (4.9% vs 35%, P < .01; χ. ICH in patients treated with VKA is associated with high mortality rates; mortality in these patients is mainly and independently associated with the clinical situation at stroke onset.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cause of Death; Cerebral Hemorrhage; Female; Humans; Middle Aged; Prognosis; Registries; Retrospective Studies; Spain; Stroke; Vitamin K; Young Adult

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: 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

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

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 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

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

Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p < 0.001). They were more likely to have had a recent TIA [odds ratio (OR) 30.1; 95% confidence interval (CI) 11.5-78.7], to have been treated by vitamin K antagonist before (OR 4.2; 95% CI 1.4-12.0) and to undergo mechanical thrombectomy (45 vs. 10%, p < 0.001). They were less likely to have a pre-stroke mRS 0-1 (OR 0.22; 95% CI 0.09-0.50). After adjustment, IHS was not associated with any of the four outcome measures. Patients with IHS are treated 17 min earlier than patients with COS, but, taking into account that they were already in the hospital, delays are still too long. Their outcome does not differ from that of patients with COS, suggesting room for improvement if delays can be reduced. IHS being frequent, pre-specified pathways should be organised.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Brain Ischemia; Female; Fibrinolytic Agents; Follow-Up Studies; Hospitalization; Humans; Intracranial Hemorrhages; Male; Mechanical Thrombolysis; Middle Aged; Prospective Studies; Stroke; Thrombolytic Therapy; Time-to-Treatment; 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

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

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

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

Topics: Administration, Oral; Atrial Fibrillation; Female; Fibrinolytic Agents; Health Knowledge, Attitudes, Practice; Humans; Male; Medication Adherence; Middle Aged; Stroke; Surveys and Questionnaires; 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

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

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

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

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

Monitoring non-vitamin K antagonist oral anticoagulants (NOAC) is usually not necessary; however, in some patients it may prove beneficial.. Patient subgroups who may profit from monitoring were identified, and methods of monitoring (including assessment of which coagulation parameters are affected by NOAC) are described.. We searched the PubMed database for each of the search terms, "NOAC", "DOAC", "rivaroxaban", "dabigatran", and "apixaban", in combination with one of the terms, "monitoring", "measurement", "measuring", or "assessment". The results were compiled and reviewed.. Monitoring is most advantageous in emergency cases with severe bleeding where drug activity needs to be assessed. It can also help in deciding for or against lysis therapy after acute stroke in patients taking NOAC. Furthermore, it can also identify compliance problems and help in planning periprocedural management. There are quantitative measurement methods which measure plasma concentrations exactly and qualitative methods which only allow for a rough estimate or a general confirmation of drug activity. Recommended quantitative measurement methods are diluted thrombin time for dabigatran, and anti-factor Xa activity (calibrated) for rivaroxaban and apixaban.. Several patient subgroups may profit from monitoring of NOAC plasma concentration. One should, however, take several issues into consideration before measurements, such as the objective of each individual measurement, possible consequences (e. g., dose adjustment), and which measurement method to pick.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Blood Coagulation Tests; Dabigatran; Dose-Response Relationship, Drug; Drug Monitoring; Emergency Service, Hospital; Hemorrhage; Humans; Intensive Care Units; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thromboembolism; 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

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

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

To determine the temporal trend in poorly-controlled anticoagulated patients.. A longitudinal study was conducted on a non-unselected sample of all patients seen in a health centre over a period of 3 years (2011-2013). Patients who received anti-vitamin K anticoagulation for at least 6 months due to non-valvular atrial fibrillation were selected, obtaining a final sample of 130 patients.. The mean age of the sample was 77.0±1.5 years and 53.1% were male. The prevalence of hypertension and diabetes mellitus was 90% and 33.8%, respectively, and 11.5% and 14.6% had had heart failure or a stroke, respectively. The mean number of medications taken by patients was 7.6±0.6. The prevalence of insufficient control of time in therapeutic range, calculated by Rosendaal, was 60.2% in 2011, 54.2% in 2010, and 43.4% in 2012. On analysing the time in the therapeutic range in patients with impaired control in the first quarter of follow-up, it was observed to remain low in subsequent years: 69.7% vs 55%, P=.0005, in 2011; 71.9% vs 59.3%, P=.0015 in 2012; and 74.7% vs 60%, P=.0005 in 2013.. Our study shows that patients with inadequate time in therapeutic range have a tendency to stay in poor control, suggesting the need for early clinical decisions in patients on anticoagulants, taking into account the prognosis and economic costs of atrial fibrillation and treatment.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Longitudinal Studies; Male; Primary Health Care; Retrospective Studies; Stroke; Time Factors; Vitamin K

It is unclear whether vitamin K antagonists affect stroke severity and outcome in patients with atrial fibrillation (AF). We aimed to evaluate this association. We prospectively studied 539 consecutive patients admitted with acute ischemic stroke (41.2 % males, age 78.9 ± 6.6 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). The outcome was assessed with dependency rates at discharge (modified Rankin scale 2-5) and with in-hospital mortality. 177 patients had a history of AF. The median NIHSS at admission did not differ between patients on acenocoumarol with INR 2.0-3.0, on acenocoumarol with INR < 2.0, on single antiplatelet treatment, on dual antiplatelet treatment, or on no treatment [4 (range 0-26), 13 (0-39), 8 (0-33), 3 (2-23) and 7 (0-33), respectively; p = 0.433]. Dependency rates were lower in patients on acenocoumarol with INR 2.0-3.0 or on dual antiplatelet treatment than in those on acenocoumarol with INR < 2.0, single antiplatelet treatment, or no treatment (20.0, 22.2, 61.5, 58.7 and 68.0 %, respectively; p = 0.024). Independent predictors of dependency were age, NIHSS at admission and history of ischemic stroke. In-hospital mortality did not differ between patients on acenocoumarol with INR 2.0-3.0, on acenocoumarol with INR < 2.0, on single antiplatelet treatment, on dual antiplatelet treatment, or on no treatment (7.7, 18.2, 16.1, 16.7 and 22.2 %, respectively; p = 0.822). In conclusion, optimally anticoagulated patients with AF have more favorable functional outcome after stroke and a trend for less severe stroke whereas patients with subtherapeutic anticoagulation have similar stroke severity and outcome with those on no treatment.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Female; Hospital Mortality; Humans; International Normalized Ratio; Male; Platelet Aggregation Inhibitors; Severity of Illness Index; Stroke; Vitamin K

Atrial fibrillation (AF) is the most common clinically-significant arrhythmia in the adult population, and it is a strong independent risk factor for cerebrovascular accidents. Patients with non-valvular AF are five times more likely to suffer a stroke. Despite the clear recommendations for anticoagulant therapy, many clinicians are still reluctant to provide routine oral anticoagulation to patients with AF, despite the potential clinical benefits.. To compare Polish and European populations of patients with AF and the every-day practice of stroke prevention in Poland and in the rest of Europe.. We analysed the baseline data from the two first cohorts of patients enrolled in the GARFIELD-AF registry (an ongoing prospective, multicentre, international registry of patients newly diagnosed with AF) in Poland and in the rest of Europe.. Polish AF patients are generally younger (median age 67 years in both cohorts vs. 73 in cohort 1 in the rest of Europe and 72 in cohort 2), but they carry a burden of more concomitant diseases. There are some noticeable differences in stroke prevention between Poland and the rest of Europe. The use of vitamin K antagonists (VKAs) is generally higher in other European countries in both cohorts (in Poland 41.7% in cohort 1 and 36.9% in cohort 2 vs. 55.5% in cohort 1 and 41.9% in cohort 2 in the rest of Europe). Meanwhile, it is generally more common in Poland to treat patients with both VKAs and antiplatelets (in cohort 1 20.4% of patients in Poland received vs. 12.0% in the rest of Europe). A total of 5.6% of patients in cohort 1 in Poland receive no antithrombotic treatment (it means: no VKA, oral factor Xa or thrombin inhibitors, antiplatelets), meanwhile in other countries it amounts to 8.5%. The usage of non-vitamin K oral anticoagulants is growing in Poland similarly to the other European countries.. The GARFIELD-AF registry data shows how distant everyday clinical practice is from the guidelines. It shows that still in Poland, as well as in the rest of Europe, too many patients with low stroke risk are treated with anticoagulants, while too frequently patients at high stroke risk are left with no stroke prevention. Although the tendency to use non-vitamin K oral anticoagulants is growing comparably in Poland and in the rest of Europe, the proportion of patients with intermediate and high stroke risk is not growing and more patients at low stroke risk are treated with anticoagulants.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Poland; Practice Guidelines as Topic; Prospective Studies; Registries; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Humans; Stroke; Vitamin K

Patients with atrial fibrillation requiring maintenance haemodialysis are at increased risk of ischaemic stroke and bleeds. Currently, vitamin K antagonists such as warfarin are predominantly used in these patients as limited data are available on the use of non-vitamin K oral anticoagulants, including dabigatran etexilate (dabigatran). Dabigatran is approximately 85 % renally eliminated, thus, its half-life is prolonged in renal impairment. This study simulated the doseexposure relationship of dabigatran in patients undergoing haemodialysis. Dabigatran exposure was modelled at once- and twice-daily doses of 75 mg, 110 mg and 150 mg and at variations in non-renal clearance and dialysis settings. Resultant dose exposure (area under the curve [AUC]) was compared with values simulated from typical patients in the RE-LY® trial (based on a previously characterised pharmacometric model). In this simulation, all twice-daily dosages resulted in exposures above those simulated from typical RE-LY patients (1.5- to 3.3-fold increase in AUC) and thus may not be optimal for use in haemodialysis patients. However, dabigatran doses of 75 mg or 110 mg once daily produced exposures comparable to those simulated in typical RE-LY patients (-13.3 and +4.4 %, respectively). Of patient and dialysis variables, non-renal clearance had the highest impact on exposure (≤ 30.8 % change). These data could potentially inform dose selection in patients undergoing maintenance haemodialysis and the findings warrant investigation in future clinical trials.

Topics: Administration, Oral; Aged; Anticoagulants; Area Under Curve; Atrial Fibrillation; Brain Ischemia; Computer Simulation; Dabigatran; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Humans; Stroke; Vitamin K

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

Non-vitamin K oral anticoagulants (NOAC) have now become established for stroke prevention in atrial fibrillation. The efficacy is at least as good if not better than that of vitamin K antagonists (VKA). The risk for major bleeding is less for NOAC than for VKA, with a particular superiority concerning the avoidance of intracerebral hemorrhage. The outcome after major bleeding is more favorable in patients receiving NOAC compared to those treated with VKA. Specific reversal agents for NOAC are currently being tested which neutralize the effects of NOAC within minutes and the clinical introduction of the first one for the thrombin inhibitor dabigatran is imminent. Such specific antidotes will further improve the safety profile of NAOC.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Evidence-Based Medicine; Hemorrhage; Humans; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Guidelines generally recommend oral anticoagulation to be considered the first 3 months after mitral valve repair based on small studies and consensus. However, in several studies no benefit of anticoagulation has been found.. From the national registries we identified all Danish patients who underwent mitral valve repair during the period between 1997 and 2012. Medication, hospitalisation and mortality data were studied. The association of use of vitamin K antagonists (VKAs) at discharge and risk of stroke/death was evaluated by means of Cox regression, landmark analyses and propensity matched models.. 2188 patients without prior VKA use, stroke or death day 7 after discharge were included and median follow-up was 4.9 years (0-13.7). 859 (39%) were discharged on VKAs and 523 (24%) experienced death or stroke, 60 of these occurred within the first 3 months and 24 between 3 and 6 months. Compared with patients without post-discharge VKA, patients on VKA had a lower risk of death/stroke at 3 months (HR=0.28, CI (0.13 to 0.62), p=0.002) and in the time period from 3 to 6 months (HR=0.85, CI (0.35 to 2.07), p=0.72). Risk of significant bleeding complications within 3 months were comparable in the two groups with 23 (2%) among patients without VKA and 6 (1%) among VKA-treated.. VKA treatment after mitral valve repair is associated with a markedly lower risk of adverse events as stroke or death without excess major bleeding risk during the first 3 months following surgery.

Topics: Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitral Valve; Postoperative Complications; Postoperative Hemorrhage; Risk Factors; Stroke; Vitamin K; Young Adult

To examine the long-term persistence and safety of the non-vitamin-K-antagonist oral anticoagulants (NOACs) dabigatran (D), rivaroxaban (R) and apixaban (A) in patients with non-valvular atrial fibrillation (AF) treated in the framework of a well structured, nurse-based AF unit for initiation and follow-up of NOAC.. Retrospective clinical data were collected for 766 consequent patients from a single cardiology outpatient clinic incorporating the AF unit.. The follow-up time, median (q1-q3), was 367 days (183-493) for D patients (n = 233), 432 days (255-546) for R patients (n = 282) and 348 days (267-419) for A patients (n = 251). No significant differences were found between the three groups with regard to age, sex, renal function, or CHA2DS2-VASc score. For all bleeding events the incidence rates per 100 patient-years of follow-up (95% confidence interval [CI], p-value) were reported more often for treatment with R (17.2, 12.7-22.8) than for D (7.0, 4.0-11.3, p = 0.001) and A (8.7, 5.2-13.6, p = 0.013). The differences remained significant after adjustment for clinically relevant variables. Discontinuation rates (n = 167) were lower for A (11.5, 7.5-16.8) than for D (30, 23.4-37.9, p < 0.001) and R (23.9, 18.6-30.1, p = 0.001), and were mainly attributed to drug-specific side effects and bleedings. The majority of discontinued patients (n = 142, 85%) proceeded with other types of oral anticoagulants.. The main limitation of the study is the small patient population with a short follow-up time.. In a retrospective study at a single AF clinic, NOACs showed significantly different bleeding rates and varied discontinuation rates when compared to each other, related mainly to agent-specific side effects and bleedings. The majority of patients that discontinued proceeded with other types of oral anticoagulant.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Safety; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

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

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; International Normalized Ratio; Male; Physician's Role; Physicians, Primary Care; Practice Patterns, Physicians'; Retrospective Studies; Spain; Stroke; Vitamin K

To assess persistence and adherence to rivaroxaban, dabigatran, and vitamin K antagonist (VKA) treatment in primary care patients with non-valvular atrial fibrillation (AF) newly starting anticoagulant therapy.. Prescription data for oral anticoagulants were obtained from 7265 eligible patients from primary care practices across Germany. Persistence with and adherence to anticoagulation were assessed in anticoagulant-naïve patients with AF newly treated with dabigatran, rivaroxaban, or VKA during follow-up periods of at least 180 days, respectively 360 days after the prescription date. Persistence probabilities after 180 days were 66.0% for rivaroxaban, 60.3% for dabigatran, and 58.1% for VKA (P < 0.001 for rivaroxaban vs. VKA and P = 0.008 for rivaroxaban vs. dabigatran). After 360 days, persistence probabilities were 53.1, 47.3, and 25.5%, respectively (P < 0.001 for rivaroxaban and dabigatran vs. VKA). Considering the development over 360 days rivaroxaban demonstrated a better persistence compared with dabigatran (P = 0.026). Male gender and the presence of diabetes mellitus were associated with increased persistence, while renal impairment and antiplatelet drug use decreased persistence. High adherence (MPR ≥0.80) was observed in 61.4% of rivaroxaban users and in 49.5% of dabigatran users, with means of 0.76 [95% confidence interval (CI) 0.74-0.78] for rivaroxaban and 0.67 (95% CI 0.65-0.69) for dabigatran (P < 0.001).. Rivaroxaban and dabigatran demonstrated better persistence than VKA at Day 360. Furthermore, rivaroxaban was associated with better persistence and adherence than dabigatran. Further studies are needed to identify factors responsible for this difference and evaluate the impact on outcomes.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation; Dabigatran; Databases, Factual; Factor Xa Inhibitors; Female; Follow-Up Studies; Germany; Humans; Logistic Models; Male; Medication Adherence; Middle Aged; Retrospective Studies; Risk Reduction Behavior; Rivaroxaban; Stroke; Vitamin K

Vitamin K antagonists are currently recommended in patients with 'valvular' atrial fibrillation (AF), e. g. those having mitral stenosis or artificial heart valves. We compared thromboembolic risk in patients with 'non valvular' AF and in those with AF and biological valve replacement (valve bioprosthesis). Among 8962 AF patients seen between 2000 and 2010, a diagnosis of 'non-valvular AF' was found in 8053 (94 %). Among patients with 'valvular' AF, 549 (6 %) had a biological prosthesis. The patients with bioprosthesis were older and had a higher CHA2DS2-VASc score than those with non valvular AF. After a follow-up of 876 ± 1048 days (median 400 days, interquartile range 12-1483), the occurrence of thromboembolic events was similar in AF patients with bioprosthesis compared to those with 'non valvular' AF (hazard ratio [HR] 1.10 95 % confidence interval [CI] 0.83-1.45, p=0.52, adjusted HR 0.93, 95 %CI 0.68-1.25, p=0.61). Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95 %CI 1.16-1.34 per 10-year increase, p< 0.0001) and higher CHA2DS2-VASc score (HR 1.35, 95 %CI 1.24-1.46, p< 0.0001) whilst female gender (HR 0.75, 95 %CI 0.62-0.90, p=0.002), use of vitamin K antagonist (HR 0.83, 95 %CI 0.71-0.98, p=0.03) were independently associated with a lower risk of stroke/TE. Neither the presence of bioprosthesis nor the location of bioprosthesis was independent predictor for TE events. In conclusion, AF patients with bioprosthesis had a non-significantly higher risk of stroke/TE events compared to patients with non-valvular AF. Second, the CHA2DS2-VASc score was independently associated with an increased risk of TE events, and was a valuable determinant of TE risk both in AF patients with non-valvular AF as well as those with bioprosthesis, whether treated or not treated with OAC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Female; France; Heart Valve Prosthesis; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke; Thromboembolism; Vitamin K

Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied.. VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-γ-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-γ-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-γ-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake.. In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Prothrombin; Risk Assessment; Risk Factors; Stroke; Time Factors; United States; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Guideline Adherence; Humans; Phenprocoumon; Stroke; Vitamin K

Recent trends in vitamin K antagonists (VKA) use in non-valvular atrial fibrillation (NVAF) are useful to evaluate the potential improvement in management of NVAF since the introduction of new oral anticoagulants. Our objective was therefore to describe the contemporary VKA treatment patterns following NVAF diagnosis.. We used the computerized databases of the Régie de l'assurance maladie du Québec (RAMQ), responsible for administering the universal health care services for all its residents, to identify a population-based cohort of 135,241 patients with an incident diagnosis of NVAF during 2000-2009 and RAMQ medication coverage. Following NVAF diagnosis, 47.1 % of the patients were prescribed VKA, 35.5 % received an antiplatelet only, and 17.4 % did not initiate antithrombotic therapy. The proportion of patients initiating VKA within 3 months of diagnosis increased from 33 % to 39 % over the 10-year study period, mainly driven by a higher proportion of treated patients aged 80 or more (from 29 % to 41 %). At the end of the study period, women were prescribed VKA as frequently as men, except in the subgroup of patients with a low risk of ischemic stroke. The median time from VKA initiation to the first discontinuation varied greatly according to the definition of discontinuation, ranging from 11 months to 5.7 years.. Although VKA remain underused after NVAF diagnosis, there has been an increase in VKA treatment over the last decade, particularly among older patients. Also the gap in treatment between men and women has been closing within the last decade. Once initiated, most VKA interruptions were temporary rather than definitive.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization Review; Female; Fibrinolytic Agents; Healthcare Disparities; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Quebec; Registries; Risk Factors; Sex Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Young Adult

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Time Factors; Vitamin K; Warfarin

Vitamin K antagonists (VKA) use is challenging because of frequent blood monitoring and complex dosing. Therefore, many patients and physicians are reluctant to start VKA. However, it is unclear whether VKA use actually lowers quality of life. We aimed to determine the impact of VKA initiation on quality of life and to analyze the correlation between patient and treatment characteristics and VKA perception in atrial fibrillation patients.. In a prospective cohort of 240 new and 567 long-term VKA users, general quality of life and VKA perception (satisfaction and convenience) were measured at inclusion and at 3 months by the validated Study Short-Form 36 and Perception of Anticoagulant Treatment Questionnaire. Scores were converted to a 0 to 100 scale. Higher scores are more favorable. In the new patients, Medical Outcomes Study Short-Form 36 scores improved during the initial 3 months to a level comparable with the general population. At 3 months, the median convenience score was 95 (Q1-Q3, 88-98) and was higher in older patients (regression coefficient, 0.47 per year; 95% confidence interval, 0.25-0.69) and lower after bleeding (regression coefficient, -12; 95% confidence interval, -20 to -4.7). The median satisfaction score was 64. For the long-term patients, VKA perception scores were highly comparable with the new patients. The convenience score mildly improved in patients with increased individual time in therapeutic range (regression coefficient, 0.03; 95% confidence interval, 0.01-0.05; r(2)=0.01), and satisfaction scores decreased in patients with new comedication (regression coefficient, -7.0; 95% confidence interval, -12 to -1.9; r(2)=0.02).. VKA were well tolerated in real-life, and the influences of patient and treatment related factors on VKA perception were very limited.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Health Knowledge, Attitudes, Practice; Humans; Longitudinal Studies; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Quality of Life; Risk Factors; Stroke; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vitamin K

The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice.. In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME.. Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; China; Drug Administration Schedule; Europe; Female; Fibrinolytic Agents; Healthcare Disparities; Hemorrhage; Humans; Male; Middle Aged; Middle East; Patient Selection; Practice Patterns, Physicians'; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

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

Essentials Anticoagulation in the elderly is still a challenge and suspension of warfarin is common. This is an observational study reporting reasons and consequences of warfarin suspension. Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension. After suspension for bleeding or frailty, patients remain at high-risk of death or complications.. Background Anticoagulation in elderly patients with non-valvular atrial fibrillation (NVAF) is still a challenge, and discontinuation of warfarin is common. The aim of this study was to analyze the aspects related to warfarin discontinuation in a real-world population. Methods This was an observational cohort study on very elderly NVAF patients naive to warfarin therapy (VENPAF). The included subjects were aged at least 80 years, and started using warfarin after a diagnosis of NVAF. Warfarin discontinuation was assessed, and the reason reported for discontinuation, the person who decided to stop treatment, subsequent antithrombotic therapy and mortality, ischemic and bleeding events were collected. Results Over a period of 5 years, warfarin was discontinued in 148 of 798 patients. Despite similar CHA

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Multivariate Analysis; Proportional Hazards Models; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Vascular Diseases; Vitamin K; Warfarin

INTRODUCTION    Most patients with atrial fibrillation (AF) are elderly and may have an increased risk of cognitive disorders. Low mean values of the therapeutic international normalized ratio (INR) range (TTR) (≤60%) are associated with increased risk of stroke, vascular events, and bleeding complications. OBJECTIVES    The aim of the study was to evaluate the efficacy of long-term anticoagulant therapy in patients treated with vitamin K antagonists (VKAs), depending on their cognitive functions. In addition, we used the SAMe-TT2R2 risk score to predict the risk of ineffective anticoagulation. PATIENTS AND METHODS The analysis comprised 154 patients (68 men and 86 women; mean age, 76 ±10 years) with AF and indications for long-term therapy with VKA (CHA2DS2-VASc score ≥1, HAS-BLED score <3). Cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) score. The efficacy of VKA therapy was determined by the TTR values from the preceding 6 months of treatment. We used the SAMe-TT2R2 score to identify patients who were likely to have poor INR control. RESULTS    Depending on the number of MMSE points, patients treated with VKAs were divided into 2 groups: patients with normal cognitive functions (MMSE score ≥27; n = 62) and those with cognitive impairment (MMSE score <27; n = 42). Despite the fact that all patients had indications for anticoagulant therapy, 50 patients (32%) received no VKAs on admission. The mean TTR value exceeded 60% in 61% of patients with an MMSE score of 27 points or higher, whereas mean TTR value was 28% in patients with an MMSE score of less than 27 (P <0.0001). Patients with a SAMe-TT2R2 score of 0 to 1 had higher TTR values than those with a SAMe-TT2R2 score of 2 or higher (r = -0.24; P <0.05 ). The cognitive status was significantly more impaired in patients with persistent and permanent AF compared with patients with paroxysmal AF (MMSE score, 25.8 ±3.7 vs 28.6 ±2; P <0.0001). CONCLUSIONS    Cognitive disorders in patients with AF significantly reduce the efficacy of VKA therapy. The decision to administer VKA treatment should be based not only on the CHA2DS2-VASc and HAS-BLED scores, but also on the SAMe-TT2R2 score and the evaluation of the patient's cognitive functions.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cognitive Dysfunction; Female; Humans; International Normalized Ratio; Male; Middle Aged; Predictive Value of Tests; Stroke; Treatment Outcome; Vitamin K

The study sought to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant atrial fibrillation (AF).. Guidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) with a vitamin K antagonist (VKA) are scarce.. A multicenter evaluation comprising 621 patients with AF undergoing TAVR was undertaken. Post-TAVR prescriptions were used to determine the antithrombotic regimen used according to the following 2 groups: monotherapy (MT) with VKA (n = 101) or multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; n = 520). Endpoint definitions were in accordance with Valve Academic Research Consortium-2 criteria. The rate of stroke, major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), major or life-threatening bleeding events, and death were assessed by a Cox multivariate model regression survival analysis according to the antithrombotic regime used.. During a median follow-up of 13 months (interquartile range: 3 to 31 months) there were no differences between groups in the rate of stroke (MT: 5%, MAT: 5.2%; adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 0.45 to 3.48; p = 0.67), major adverse cardiovascular events (MT: 13.9%, MAT: 16.3%; adjusted HR: 1.33; 95% CI: 0.75 to 2.36; p = 0.33), and death (MT 22.8%, MAT: 19.2%; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; p = 0.76). A higher risk of major or life-threatening bleeding was found in the MAT group (MT: 14.9%, MAT: 24.4%; adjusted HR: 1.85; 95% CI: 1.05 to 3.28; p = 0.04). These results remained similar when patients receiving VKA plus only 1 antiplatelet agent (n = 463) were evaluated.. In TAVR recipients prescribed VKA therapy for AF, concomitant antiplatelet therapy use appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Atrial Fibrillation; Brain Ischemia; Canada; Chi-Square Distribution; Europe; Female; Heart Valve Diseases; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Stroke; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Stroke; Vitamin K

Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation.. Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference.. In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72-3.75) for bleeding and of 1.41 (0.66-3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40-14.5).. Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding.

Topics: Aged; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Denmark; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Postoperative Hemorrhage; Registries; Stroke; Vitamin K

This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians' adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3.The suboptimal use of NOACs is common because of physicians' poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Guideline Adherence; Hemorrhage; Humans; Practice Guidelines as Topic; Prospective Studies; Registries; Risk Factors; Stroke; Turkey; Vitamin K

Stroke prevention in dialysis-dependent patients with atrial fibrillation (AF) is an unresolved clinical dilemma. Indeed, no randomized controlled trial evaluating the efficacy and safety of oral anticoagulants in this population, has been conducted so far. Observational research on the use of warfarin in patients on dialysis has shown conflicting results. This uncertainty is mirrored by the wide variations in warfarin prescription patterns across centers. We sought to evaluate the association between the use of vitamin K antagonists (VKAs) and mortality among hemodialysis patient with AF and to assess potential factors affecting the risk-benefit profile of warfarin in this population.. A total of 91,987 patients registered in the European Clinical Dialysis Database® system from January 2004 to January 2015. Of which, 9,238 patients were identified with a diagnosis of AF. After excluding ineligible patients, a 1:1 propensity score matched cohort of 1,324 warfarin users and non-users were assembled.. VKA use was associated with both increased 90-day survival (hazard ratio, HR 0.47, p < 0.01) and 6-year survival (HR 0.76, p < 0.01); however, a trend indicated a stronger early benefit (p for time-interaction <0.01). Moderation analysis showed that patients' age and clinical history of stroke strongly influenced warfarin-related benefits on survival.. VKA may provide an early survival benefit; however, this is partially offset later during the follow-up. In addition, heterogeneous risk-benefit profiles were observed among subgroups of dialysis-dependent patients with AF, further emphasizing the complexities of tailoring stroke prevention strategies in this population.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Humans; Kidney Failure, Chronic; Middle Aged; Mortality; Propensity Score; Registries; Renal Dialysis; Risk Assessment; Stroke; Survival Rate; Time Factors; Vitamin K; Warfarin

Atrial fibrillation is the commonest cardiac rythm disorder. Thromboembolic accidents are common complications that should be prevented by anticoagulant treatment. The aim of our study is to assess the use of vitamins K antagonists in the prevention of thromboembolic risk in atrial fibrillation.. It was a descriptive retrospective study of patients folders, performed in the cardiology department from January 1st 2010 to December 31st 2011. The study included all patients with non valvular atrial fibrillation. Thromboembolic risk was assessed through the CHA2DS2VASc score, and hemorrhagic risk through the HAS-BLED score.. Atrial fibrillation accounted for 10.6% of all hospitalizations (103/970). Five patients had contra indication to anticoagulants. Non valvular AF was noticed in 68 cases (66%). The non valvular AF was chronic in 40 cases (59%) and paroxystic in eight cases (12%). The median age of the population was 64.5+13.8 years old. Median CHA2DS2VASc score was 3.9 + 1.6. Two patients had a score < 1. Sex, place of residence, age > 65, and cardiac failure did not interfere with prescription of vitamins K antagonists. Ischemic stroke and intra cavity thrombus were the indications for vitamins K antagonists' prescriptions. The median HAS-BLED score was 3.5 + 1.5. The rate of vitamins K antagonists use was 35.3%. One case of death due to hemorrhagic stroke was noticed.. Guidelines on thromboembolic risk prevention are poorly used in the cardiology department. But the use of scoring systems allows the assessment of vitamins K antagonists treatment benefit/risk in atrial fibrillation, and minimizes the hemorrhagic risk.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Burkina Faso; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Thromboembolism; Vitamin K

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

Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation.. We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy.. Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last.. Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Female; Humans; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Septal Occluder Device; Stroke; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Hemorrhage; Humans; Incidence; Stroke; Thromboembolism; Vitamin K

Successful vitamin K antagonist (eg, warfarin) reversal with 4-factor prothrombin complex concentrate (4F-PCC) without vitamin K (phytonadione) for emergent surgery in a patient at moderate-to-high risk for thromboembolism is reported. This approach may decrease the risk for development of thrombus, as it limits the amount of time the patient's anticoagulation is subtherapeutic. It also may increase the risk of bleeding, so patient selection is essential if this strategy is employed. Caution must be exercised to complete the procedure or surgery in the window of peak 4F-PCC effect (∼1-6 hours postinfusion).

Topics: Accidents, Traffic; Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation Factors; Compartment Syndromes; Crush Injuries; Drug Hypersensitivity; Fibula; Fractures, Bone; Humans; International Normalized Ratio; Leg Injuries; Male; Preoperative Care; Stroke; Vitamin K; Warfarin

Vitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0-3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality.. TTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027).. A large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes.. ClinicalTrials.gov NCT01090362.

Topics: Anticoagulants; Antiplatyhelmintic Agents; Atrial Fibrillation; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Registries; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Vitamin K is involved in brain physiology, suggesting that its deficiency induces cognitive decline. Our objective was to determine whether using vitamin K antagonists (VKAs) was associated with cognitive impairment among geriatric patients.. Two hundred sixty-seven older patients (mean, 83.4 ± 8.1 years; 56.9% female) were categorized according to cognitive impairment (ie, Mini-Mental State Examination ≤ 25). The regular use of VKAs was sought by questioning the patients, relatives, and family physicians. Age, gender, body mass index, comorbidity burden, mood and executive functioning, history of atrial fibrillation, ischemic stroke, intracranial hemorrhage and transient ischemic attack, use of other anticoagulants and antiplatelet medications, and severe renal failure were used as potential confounders.. Compared with participants without cognitive impairment (n = 70), those with Mini-Mental State Examination ≤ 25 used more frequently VKAs (p = .038). The risk of cognitive impairment was 15% higher with VKAs, specifically with fluindione. Using VKAs was independently associated with cognitive impairment (fully adjusted odds ratio = 17.4 [95% CI: 1.4-224.2], p = .028).. We found more frequent cognitive impairment associated with the use of VKAs, specifically fluindione, among geriatric patients.

Topics: Aged; Aged, 80 and over; Aging; Anticoagulants; Atrial Fibrillation; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Male; Mental Status Schedule; Phenindione; Pilot Projects; Risk Factors; Stroke; Vitamin K

Effective anticoagulation with vitamin K antagonists (VKAs) is the standard of stroke prevention in patients with non-valvular atrial fibrillation (AF). Although, everyday practice is becoming increasingly guideline-driven, proper anticoagulation is still problematic. We aimed to investigate changes in the use of VKAs for stroke prevention in patients with AF admitted because of acute stroke over a period of 15 years.. We analysed consecutive acute stroke patients admitted to our centre between June 1995 and December 2010. Data were prospectively collected in a detailed stroke registry. We distinguished between three periods: 1995-2000 (used as reference for comparisons), 2001-2005 and 2006-2010.. The AF rate prior to stroke was similar in ischaemic stroke patients (1995-2000: 25%, 2001-2005: 24%, 2006-2010: 24%) but increased in patients with intracerebral haemorrhage (ICH) (6%, 11%, 19%, p = 0.003 since 2006). The proportion of patients with AF using VKAs before stroke has became higher in ischaemic stroke (10%, 16%, 28%, p < 0.001 since 2006) with non-significant trend in ICH (0%, 33%, 45%). The proportion of ischaemic strokes occurring in patients with AF using VKAs with INR < 2 tended to increase over time (58%, 83%, 80.3%). There was also tendency towards increasing proportion of ICHs occurring in patients with AF over treated with VKAs (INR > 3).. The prescription rate of VKA for stroke prevention appears to be improving. However, because of a high proportion of patients on non-therapeutic INR, the proportion of cardioembolic ischaemic strokes remains stable. It may suggest that everyday use of VKAs is still far from optimal.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Stroke; Vitamin K

Atrial fibrillation (AF) is increasingly prevalent in the elderly, but such patients tend to be under-represented in clinical trials. Increasing age confers a higher risk of stroke and bleeding when antithrombotic therapy is used. We examined risk factors for stroke and bleeding among elderly (age, >75 years) patients within a real world hospitalized cohort from the Loire Valley AF project.. We identified elderly (age, >75 years) patients with AF, assessed their risk factors, and followed up for stroke, thromboembolism, death, or major bleeding. The effect of vitamin K antagonist (VKA) use on these end points was assessed.. We studied 8962 patients with AF, and we identified 4130 elderly (age, ≥75 years) patients. Using Kaplan-Meier analyses, event rates of death, stroke/thromboembolism, the composite of stroke/thromboembolism/death, and major bleeding increased with increasing age. For mortality, VKA-treated patients did better than non-VKA-treated patients. The risk of death and stroke/thromboembolism/death increased with increasing age. The risk of major bleeding did not increase with increasing age strata. VKA treatment was associated with lower mortality in those aged <75 years (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45-0.72), and the effect size was maintained with increasing age strata (Pint=0.67). For stroke/thromboembolism/death, VKA also has a significant benefit in those aged <75 years (adjusted HR, 0.69; [0.57-0.83]), and the effect size was maintained with increasing age strata (Pint=0.58). For major bleeding, there was no statistically significant difference between age strata (Pint=0.67). In elderly patients, age and previous stroke emerged as the main predictors of stroke and thromboembolism. Renal impairment and VKA use were predictors of major bleeding.. Elderly patients with AF have a higher risk of stroke and bleeding, but the benefits of VKA therapy for stroke/thromboembolism or mortality were present regardless of increasing age.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Platelet Aggregation Inhibitors; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

Topics: Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; International Normalized Ratio; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Vitamin K; Warfarin

We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE.. At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug.. Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial.. The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation.

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Risk Assessment; Stroke; Vitamin K; Warfarin

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

Clinicians need to get better at identifying patients who would have poor quality of anticoagulation control with vitamin-K antagonists (VKAs). We assessed the predictive ability of SAMe-TT2R2 score, recently conceived for the prior purpose, and examined its relationship with major bleeding, thromboembolic (TE) complications, and death.. Retrospectively, 911 consecutive patients with non-valvular atrial fibrillation (NVAF) started on VKAs within 8 months were studied. The percentage of international normalized ratios in therapeutic range (PINRR) at different levels was used as a metric of anticoagulation quality. We also tested the SAMe-TT2R2 predictability for major bleeding, TE complications, and death throughout 10 ± 3 months. The PINRR decreased from 62% at zero point to 53% at ≥4 points of SAMe-TT2R2. 82.1% of patients who achieved PINRR ≥ 70% had 0 or 1 point of SAMe-TT2R2. SAMe-TT2R2 performed significantly better at PINRR 70% than at 65 and 60% (c-statistic = 0.60 vs. c-statistic = 0.56). The calibration of SAMe-TT2R2 was excellent (Hosmer-Lemeshow test P-values ≥ 0.6). SAMe-TT2R2 showed significant association with the composite outcome of major bleeding, TE complications, and death [n = 98; hazard ratio (HR) = 1.32; 95% confidence interval (CI) 1.08-1.60]; the c-statistic was 0.57 (95% CI: 0.51-0.62) and P = 0.03. As individual outcomes, SAMe-TT2R2 was significantly associated with death (n = 60; HR = 1.3; 95% CI: 1.03-1.69), but not with either major bleeding (n = 30; HR = 1.2; 95% CI: 0.85-1.76) or TE complications (n = 15; HR = 1.01; 95% CI: 0.58-1.77).. Among NVAF patients, SAMe-TT2R2 could represent a useful clinical tool to identify patients who would have poor quality of anticoagulation control with VKAs. SAMe-TT2R2 successfully predicts the composite outcome of major bleeding, TE complications, and death.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Decision Support Techniques; Drug Monitoring; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Patient Selection; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Vitamin K

This study evaluated the rates of new lesions on diffusion-weighted images (DWIs) of magnetic resonance imaging (MRI) and hemorrhagic transformation (HT) during 2 weeks after acute ischemic stroke (AIS) in patients with atrial fibrillation (Af) who were given one of the non-vitamin K antagonist oral anticoagulants (NOACs); this was then compared with those who were given warfarin.. Consecutive AIS patients with Af were enrolled between January 2008 and June 2013, and those selected were patients who had a MRI that included DWIs both on admission and after 2 weeks, and those given only wafrarin (warfarin group) or only one of the NOACs (NOAC group) within 2 weeks of admission. Of all 257 enrolled patients, 50 patients were selected for the NOAC group (median age of 80.0 years) and 125 patients for the warfarin group (median age of 80.0 years). Both NOAC and warfarin were started at a median of the second day after admission. There was no significant difference in the rates of new lesions on DWIs (26.0% vs. 28.0%, P=0.7888) and HT (30.0% vs. 39.2%, P=0.2536) between the NOAC and warfarin groups. The NOAC group had a lower rate of concomitant use of heparin (44.0% vs. 92.8%, P<0.0001) than the warfarin group.. This study suggests that NOACs are suitable for AIS patients with Af, perhaps even better than warfarin, given their simplicity.

Topics: Acute Disease; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Heparin; Humans; Magnetic Resonance Imaging; Male; Radiography; Stroke; Time Factors; Vitamin K; Warfarin

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients 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).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors.. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method.. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011).. There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Male; Prevalence; Retrospective Studies; Spain; Stroke; Time Factors; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Decision Support Techniques; Female; Humans; Male; Stroke; Thromboembolism; Vitamin K

An estimated 20% of ischemic strokes are of cardiogenic origin, half of which is associated with atrial fibrillation (AF). Anticoagulation treatment of patients with this arrhythmia reduces their risk of stroke. Effectiveness and safety of oral anticoagulant therapy with vitamin K antagonists (VKA) is limited, however, by their well-known narrow therapeutic window and the substantial inter- and intraindividual variability of INR values depending on genetic and dietary factors as well as drug interactions. Our objective was to evaluate the prevalence of adequate anticoagulation and the level of anticoagulant effect actually achieved among patients with AF hospitalized for acute stroke.. Patients with AF admitted to our hospital ward in 2012 for acute stroke (n = 226) were included in the analysis. Using descriptive statistics, relevant clinical and therapeutic characteristics of the patients were assessed, with special reference to the INR values on admission (among patients with known AF), and the clinical outcomes.. Of the study cohort, 170 patients had a diagnosis of AF before the admission for stroke, but 47% of them did not take anticoagulants. Patients who suffered stroke while on anticoagulants (83 on VKA, 7 on low-molecular-weight heparins), were in most cases (75%) out of the therapeutic INR range, typically undertreated (INR < 2). Overall, inadequate or completely absent anticoagulation was documented in 81% of the stroke cases occurring in patients with known AF. Of the entire study cohort, 41% was discharged home, 34% required continued institutional care, and 25% died.. The inadequacy or lack of anticoagulation was observed in the vast majority of acute strokes in patients with known AF. These cases are often related to the well-documented limitations of VKA therapy in terms of its safety, tolerability and/or practical aspects. To prevent them, important changes are warranted in the anticoagulation practice, including the closer control of VKA therapy and the broader use of new oral anticoagulants.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Heparin, Low-Molecular-Weight; Humans; Hungary; International Normalized Ratio; Male; Middle Aged; Stroke; Treatment Outcome; Vitamin K

Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration (AMD).. We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti-VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive.. A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile.

Topics: Anticoagulants; Drug Interactions; Female; Humans; International Normalized Ratio; Intravitreal Injections; Macular Degeneration; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Stroke; Time Factors; Vitamin K

Rivaroxaban has become an alternative to vitamin-K antagonists (VKA) for stroke prevention in non-valvular atrial fibrillation (AF) patients due to its favourable risk-benefit profile in the restrictive setting of a large randomized trial. However in the primary care setting, physician's motivation to begin with rivaroxaban, treatment satisfaction and the clinical event rate after the initiation of rivaroxaban are not known.. Prospective data collection by 115 primary care physicians in Switzerland on consecutive nonvalvular AF patients with newly established rivaroxaban anticoagulation with 3-month follow-up.. We enrolled 537 patients (73±11years, 57% men) with mean CHADS2 and HAS-BLED-scores of 2.2±1.3 and 2.4±1.1, respectively: 301(56%) were switched from VKA to rivaroxaban (STR-group) and 236(44%) were VKA-naïve (VN-group). Absence of routine coagulation monitoring (68%) and fixed-dose once-daily treatment (58%) were the most frequent criteria for physicians to initiate rivaroxaban. In the STR-group, patient's satisfaction increased from 3.6±1.4 under VKA to 5.5±0.8 points (P<0.001), and overall physician satisfaction from 3.9±1.3 to 5.4±0.9 points (P<0.001) at 3months of rivaroxaban therapy (score from 1 to 6 with higher scores indicating greater satisfaction). In the VN-group, both patient's (5.4±0.9) and physician's satisfaction (5.5±0.7) at follow-up were comparable to the STR-group. During follow-up, 1(0.19%; 95%CI, 0.01-1.03%) ischemic stroke, 2(0.37%; 95%CI, 0.05-1.34%) major non-fatal bleeding and 11(2.05%; 95%CI, 1.03-3.64%) minor bleeding complications occurred. Rivaroxaban was stopped in 30(5.6%) patients, with side effects being the most frequent reason.. Initiation of rivaroxaban for patients with nonvalvular AF by primary care physicians was associated with a low clinical event rate and with high overall patient's and physician's satisfaction.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Primary Health Care; Prospective Studies; Risk Factors; Rivaroxaban; Stroke; Switzerland; Treatment Outcome; Vitamin K

Vitamin K antagonists (VKA) have a narrow therapeutic range, and literature analysis reveals poor quality of anticoagulation control. We sought to assess the prevalence of poor anticoagulant control in patients under VKA treatment in the prevention of stroke for atrial fibrillation (AF).. Control of anticoagulation with VKA is inadequate in a high percentage of patients with AF.. Patients with AF under VKA treatment were prospectively recruited in this observational registry. The sample comprised 948 patients. The estimated time spent in the therapeutic range (TTR) was calculated, and variables related with a TTR >65% were analyzed.. Mean age was 73.8 ± 9.4 years, and 42.5% of the patients were women. Mean TTR was 63.77% ± 23.80% for the direct method and 60.27% ± 24.48% for the Rosendaal method. Prevalence of poor anticoagulation control was 54%. Variables associated with good anticoagulation control were university studies (odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.08-3.64), chronic hepatic disease (OR: 8.15, 95% CI: 1.57-42.24), low comorbidity expressed as Charlson index (OR: 0.87, 95% CI: 0.76-0.99), no previous cardiac disease (OR: 0.64, 95% CI: 0.41-0.98), lower risk of bleeding assessed as hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly age, and use of drugs or alcohol (HAS-BLED; OR: 0.81, 95% CI: 0.69-0.95), and lower heart rate (OR: 0.99, 95% CI: 0.98-0.99).. Patients who receive VKA to prevent stroke for AF spend less than half the time within therapeutic range.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Prospective Studies; Quality of Health Care; Registries; Stroke; Vitamin K

The percentage of time in therapeutic range (TTR) is a measure of anticoagulation quality with vitamin K antagonists (VKAs). The method most commonly used in clinical trials is the Rosendaal TTR. However, the application of this method in daily practice for clinical decision lacks appropriate instruments. We aimed to evaluate the percentage of tests within the target international normalized ratio (INR) (tests ratio) as a surrogate of Rosendaal TTR. We performed an observational and retrospective study to evaluate the TTR according to the Rosendaal method and tests ratio. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0. Three hundred and seventy-seven VKA-treated patients followed for a mean 1.3 years were evaluated. Rosendaal methold and tests ratio significantly correlated (Rho Spearman 0.88, P < 0.001), but the Bland-Altman plot evaluation showed a clinically relevant data dispersion [95% confidence interval (95% CI) -12.9 to 23.1] around a mean difference in TTR -5.1% using the tests ratio method. The linear regression Passing-Bablok confirmed the existence of significant data dispersion and systematic differences. The tests ratio less than 60% had a sensitivity of 91.6%, specificity of 72.3%, positive predictive value (PPV) of 72.2% and negative predictive value (NPV) of 91.6%, for the diagnosis of patients inadequately anticoagulated (Rosendaal TTR <60%). Tests ratio had a c-statistics of 0.94 (95% CI 0.91-0.96). Number of tests in 6 months had a c-statistics of 0.70 (95% CI 0.65-0.75). Tests ratio underestimated TTR in 5% and was not considered equivalent to Rosendaal TTR due to the high variability between methods. Nevertheless, the use of tests ratio less than 60% may be a reasonable option to detect inadequate anticoagulation, as it is a sensitive method and excluded most of the patients with adequate control.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; International Normalized Ratio; Linear Models; Male; Outpatients; Predictive Value of Tests; Retrospective Studies; Stroke; Venous Thromboembolism; Vitamin K

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Factor Xa Inhibitors; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Morpholines; Multicenter Studies as Topic; Myocardial Infarction; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; Risk; Rivaroxaban; Stroke; Thiophenes; Thrombophilia; Time Factors; Treatment Outcome; Vitamin K; Warfarin

To determine the current status of anticoagulation control in patients with nonvalvular atrial fibrillation treated with vitamin K antagonists in the primary care setting in Spain.. The PAULA study was a multicenter cross-sectional/retrospective observational study conducted throughout Spain. The study included patients with nonvalvular atrial fibrillation who had been receiving vitamin K antagonist therapy during the past year and were attended at primary care centers. International normalized ratio (INR) values over the past 12 months were recorded. The degree of anticoagulation control was defined as the time the patient had remained within the therapeutic range and was determined by both the direct method (poor control < 60%) and by the Rosendaal method (poor control < 65%).. The study assessed 1524 patients (mean age, 77.4 ± 8.7 years; 48.6% women; 64.2% in permanent atrial fibrillation; CHADS2 mean, 2.3 ± 1.2; CHA2DS2-VASc, 3.9 ± 1.5, and HAS-BLED, 1.6 ± 0.9). The mean number of INR readings recorded per patient was 14.4 ± 3.8. A total of 56.9% of patients had adequate INR control according to the direct method and 60.6% according to the Rosendaal method. The multivariate analysis identified the following predictors for poor INR control: female sex, dietary habits potentially affecting anticoagulation with vitamin K antagonists, multidrug therapy, and a history of labile INR.. Approximately 40% of patients (43.1% by the direct method and 39.4% by the Rosendaal method) with nonvalvular atrial fibrillation who were receiving anticoagulation therapy with vitamin K antagonists in primary care in Spain had poor anticoagulation control during the previous 12 months.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Primary Health Care; Retrospective Studies; Risk Factors; Spain; Stroke; Time Factors; Treatment Outcome; Vitamin K

Vitamin K antagonists are commonly used for the prevention of thromboembolic events. Patient self-monitoring of vitamin K antagonists has proved superior to usual care. Dabigatran has been shown, relative to warfarin, to reduce thromboembolic events without increasing bleeding.. We constructed a Markov model to compare vitamin K self-monitoring strategies to dabigatran including effectiveness and costs of monitoring and complications (thromboembolism and major bleeding). The model was used to project the incidence of these complications, life years, quality-adjusted life years, and health system costs with anticoagulant treatment throughout life. The analysis was conducted from the health system perspective and from the societal perspective.. Low quality evidence suggests that self-monitoring is at least as effective as dabigatran for the outcomes of thrombosis, bleeding and death. Moderate quality evidence that patient self-monitoring is more effective than other forms of monitoring degree of anticoagulation with vitamin K antagonists, reducing the relative risk of thromboembolism by 41% and death by 34%. The cost per quality adjusted year gained relative to other warfarin monitoring strategies is well below 30,000 € in the short term, and is a dominant alternative from the fourth year. In comparison with dabigatran, the lower annual cost and its equivalence in terms of effectiveness made self-monitoring the dominant option. These results were confirmed in the probabilistic sensitivity analysis.. We have moderate quality evidence that self-monitoring of vitamin K antagonists is a cost-effective alternative compared with hospital and primary care monitoring, and low quality evidence, compared with dabigatran. Our analyses contrast with the available cost analysis of dabigatran and usual care of anticoagulated patients.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Monitoring; Fibrinolytic Agents; Hemorrhage; Humans; Male; Markov Chains; Quality-Adjusted Life Years; Self Care; Stroke; Thrombosis; Vitamin K; Warfarin

The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) was designed to provide prospectively collected information on patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke, with the aim of addressing treatment patterns and questions of effectiveness and safety.. In this predefined analysis from GLORIA-AF, the baseline characteristics and initial antithrombotic management of the first 10,000 patients in Phase II of this large Registry Program are presented. Overall, 32.3% of patients received vitamin K antagonists (VKAs) and 47.7% received non-VKA oral anticoagulants (NOACs), while 12.3% received antiplatelet treatment and 7.6% did not receive any antithrombotic treatment. Among patients with CHA2DS2-VASc score ≥2, 6.7% received no antithrombotic treatment and 10.0% received aspirin. In Europe, treatment with dabigatran was as common as treatment with VKAs (38.8% and 37.8%, respectively). More than half of the patients were treated with NOACs (52.4%), while antiplatelet treatment was given to 5.7%, and 4.1% did not receive any antithrombotic treatment. In North America, treatment with dabigatran (25.0%) was as common as with VKAs (26.1%), but overall NOAC use was more common (52.1%) than with VKAs (26.1%); however, 14.1% received antiplatelet treatment, while 7.6% received no antithrombotic treatment. In Asia, treatment with VKAs (31.9%) was more prevalent than NOACs (25.5%), but antiplatelet treatment was given to 25.8%, and 16.9% did not receive any antithrombotic treatment. In Asia, only 60.7% of patients with high stroke risk received oral anticoagulants (OACs). Paroxysmal atrial fibrillation and minimally symptomatic (or asymptomatic) patients were often undertreated with OACs.. In this analysis, OAC use was high in Europe and North America, with overall NOAC use higher than VKA use. A considerable percentage of high-risk patients in North America still received antiplatelet treatment or were untreated, while Asian patients had a high proportion of aspirin use and nontreatment.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Dabigatran; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Registries; Stroke; Treatment Outcome; Vitamin K

Anticoagulation using vitamin K antagonists (VKAs) significantly reduces the risk of recurrent stroke in stroke patients with atrial fibrillation (AF) and is recommended by guidelines.. The German Competence NETwork on Atrial Fibrillation established a nationwide prospective registry including 9,574 AF patients, providing the opportunity to analyse AF management according to German healthcare providers.. On enrolment, 896 (9.4 %) patients reported a prior ischaemic stroke or transient ischaemic attack. Stroke patients were significantly older, more likely to be female, had a higher rate of cardiovascular risk factors, and more frequently received anticoagulation (almost exclusively VKA) than patients without prior stroke history. Following enrolment, 76.4 % of all stroke patients without VKA contraindications received anticoagulation, which inversely associated with age (OR 0.95 per year; 95 % CI 0.92-0.97). General practitioners/internists (OR 0.40; 95 % CI 0.21-0.77) and physicians working in regional hospitals (OR 0.47; 95 % CI 0.29-0.77) prescribed anticoagulation for secondary stroke prevention less frequently than physicians working at university hospitals (reference) and office-based cardiologists (OR 1.40; 95 % CI 0.76-2.60). The impact of the treating healthcare provider was less evident in registry patients without prior stroke.. In the AFNET registry, anticoagulation for secondary stroke prevention was prescribed in roughly three-quarters of AF patients, a significantly higher rate than in primary prevention. We identified two factors associated with withholding oral anticoagulation in stroke survivors, namely higher age and-most prominently-treatment by a general practitioner/internist or physicians working at regional hospitals.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiology; Female; General Practitioners; Germany; Guideline Adherence; Hospitals; Hospitals, University; Humans; Internal Medicine; Ischemic Attack, Transient; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prospective Studies; Registries; Risk Factors; Secondary Prevention; Stroke; Survivors; Vitamin K; Warfarin; Young Adult

Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients.. We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death.. Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE.. TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Myocardial Infarction; Patient Outcome Assessment; Proportional Hazards Models; Prospective Studies; Regression Analysis; Stroke; Vitamin K; Warfarin

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

Cervical artery dissection (CeAD) patients with or without stroke are frequently treated with either antiplatelet agents or vitamin K antagonists (VKAs), but few data are reported on the use of nonvitamin K oral anticoagulants (NOACs).. Between November 2011 and January 2014, we recorded data from patients with a stroke due to vertebral (VAD) or internal carotid artery dissection (ICAD). Patients using oral anticoagulants were included in the study and were divided into two treatment groups: patients using NOACs and those using VKAs. Excellent outcome was defined on modified Rankin Scale (mRS) ≤1 at 6 months.. Of 68 stroke patients (67% male; median age 45 [39-53]), six (8.8%; two with VAD and four with ICAD) were treated with NOACs: three with direct thrombin inhibitor dabigatran and three with direct factor Xa inhibitor rivaroxaban. National Institutes of Health Stroke Scale score at baseline was 4 (3-7) in the NOAC versus 2 (1-7) in the VKA groups. Complete recanalization at 6 months was seen in most patients in the NOAC (n = 5; 83%) and VKA (n = 34; 55%) groups. All the patients using NOACs had mRS ≤1 at 6 months and none had an intracerebral hemorrhage (ICH). In the VKA group most patients (n = 48; 77%) had mRS ≤1, one patient (1.7%) had an ICH and one died.. In this small, consecutive single-center patient sample treating ischemic stroke patients with CeAD with NOACs did not bring up safety concerns and resulted in similar, good outcomes compared to patients using VKAs.

Topics: Administration, Oral; Adult; Anticoagulants; Carotid Artery, Internal, Dissection; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Retrospective Studies; Secondary Prevention; Stroke; Treatment Outcome; Vitamin K

Renal insufficiency increases the risk of stroke and bleeding in atrial fibrillation patients. Although vitamin K antagonists reduce the risk of stroke in patients with moderate renal dysfunction, this observation is less clear in patients with renal impairment. Moreover, the risk of bleeding with vitamin K antagonists increases as renal function worsens. Maintaining international normalized ratio values within therapeutic targets is more difficult in patients with renal dysfunction, and those agents may cause warfarin-related nephropathy and vascular calcification. Rivaroxaban is the only nonvitamin K oral anticoagulant with a dose specifically tested in patients with moderate renal insufficiency. Rivaroxaban is effective for the prevention of stroke in atrial fibrillation patients with moderate renal dysfunction, with a lower risk of intracranial and fatal bleeding.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Vitamin K; Warfarin

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

Stroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients with AF are not anticoagulated, with severe consequences for stroke prevention. We aimed to determine the outcome of an innovative Primary Care AF (PCAF) service on anticoagulation uptake in a cohort of high-risk patients with AF in the UK.. The PCAF service is a novel cooperative pathway providing specialist resources within general practitioner (GP) practices. It utilises a four-phase protocol to identify high-risk patients with AF (CHA2DS2-VASc ≥ 1) who are suboptimally anticoagulated, and delivers Consultant-led anticoagulation assessment within the local GP practice. We assessed rates of anticoagulation in high-risk patients before and after PCAF service intervention, and determined compliance with newly-initiated anticoagulation at follow-up.. The PCAF service was delivered in 56 GP practices (population 386,624; AF prevalence 2.1%) between June 2012 and June 2014. 1579 high-risk patients with AF with suboptimal anticoagulation (either not taking any anticoagulation or taking warfarin but with a low time-in-therapeutic-range) were invited for review, with 86% attending. Of 1063 eligible patients on no anticoagulation, 1020 (96%) agreed to start warfarin (459 (43%)) or a non-vitamin K antagonist oral anticoagulant (NOAC, 561 (53%)). The overall proportion of eligible patients receiving anticoagulation improved from 77% to 95% (p<0.0001). Additionally, 111/121 (92%) patients suboptimally treated with warfarin agreed to switch to a NOAC. Audit of eight practices after 195 (185-606) days showed that 90% of patients started on a new anticoagulant therapy had continued treatment. Based on data extrapolated from previous studies, around 30-35 strokes per year may have been prevented in these previously under-treated high-risk patients.. Systematic identification of patients with AF with high stroke-risk and consultation in PCAF consultant-led clinics effectively delivers oral anticoagulation to high-risk patients with AF in the community.

Topics: Anticoagulants; Atrial Fibrillation; Consultants; General Practice; Health Facilities; Health Services; Humans; Patient Compliance; Primary Health Care; Risk Assessment; Stroke; Vitamin K; Warfarin

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

Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions.. We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013.. Of 17,410 participants, 6705 switched to a NOAC (switchers) and 10,705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67-82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8.1 months (IQR 3.9-14.0). After a median follow-up of 10.0 months (IQR 9.8-10.0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0.54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0.87; 95% CI 0.67-1.13, p=0.30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0.78, 95% CI 0.54-1.09, p=0.15), switchers from a vitamin K antagonist to rivaroxaban (HR 1.04, 95% CI 0.68-1.58, p=0.86), and non-switchers.. In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed.. None.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Phenindione; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin

Topics: Adolescent; Adult; Age Factors; Brain Ischemia; Female; Humans; Male; Platelet Aggregation Inhibitors; Protein S Deficiency; Retrospective Studies; Risk Factors; Sjogren's Syndrome; Sneddon Syndrome; Stroke; Vitamin K

Although risk factors for MI have been described in the general population, there is a lack of data on the assessment of risk factors associated with MI in venous thromboembolism (VTE) patients.. The purpose of this study was to identify risk factors associated with MI in VTE patients.. Health insurance claims between January 2004 and September 2008 from the Ingenix IMPACT database were analyzed. Patients aged ≥18 years were identified as of the date of their first VTE diagnosis with ≥1 year of continuous insurance coverage before the index VTE. The risk of MI for VTE patients with 1, 2, and ≥3 major risk factors as identified by published guidelines was calculated. Multivariate Cox proportional hazard models were conducted to identify the most predictive risk factors associated with MI.. A total of 177,885 VTE patients were identified; 4412 (2.5%) developed an MI during a mean follow-up period of 1.3 years. Previous MI, age (≥65 years), and coronary artery disease were the most predictive risk factors of MI with adjusted hazard ratios (HRs; 95% CI) of 5.47 (5.01-5.97), 1.78 (1.66-1.91), and 1.60 (1.48-1.74), respectively. Adjusted HRs (95% CI) for VTE patients with 1, 2, and ≥3 major risk factors relative to no major risk factor were 2.34 (1.94-2.81), 3.21 (2.67-3.85), and 6.93 (5.85-8.22), respectively.. These included possible inaccuracies or omissions in diagnoses, classification bias such as the identification of false-positive MI events, and the likely undercoding of some risk factors such as social issues.. Traditional major cardiovascular risk factors are also predictive of MI in VTE patients. Having multiple major risk factors significantly increases the probability of developing MI events in VTE patients.

Topics: Anticoagulants; Antihypertensive Agents; Cohort Studies; Coronary Artery Disease; Female; Humans; Insurance, Health; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Risk Factors; Stroke; Venous Thromboembolism; Vitamin K

The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease.. Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA.. In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Comorbidity; Coronary Artery Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticlopidine; Vitamin K; Warfarin

Warfarin, a vitamin K antagonist (VKA), has been the standard of care for stroke prevention in patients with atrial fibrillation (AF). Aspirin is recommended for low-risk patients and those unsuitable for warfarin. Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies, respectively, and causes less bleeding than warfarin. We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective.. A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients, respectively. Clinical events considered in the model include ischaemic stroke, haemorrhagic stroke, intracranial haemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, cardiovascular hospitalization and treatment discontinuations; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model. Apixaban was projected to increase life expectancy and quality-adjusted life years (QALYs) compared with warfarin and aspirin. These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime. The estimated incremental cost-effectiveness ratio was £11 909 and £7196 per QALY gained with apixaban compared with warfarin and aspirin, respectively. Sensitivity analyses indicated that results were robust to a wide range of inputs.. Based on randomized trial data, apixaban is a cost-effective alternative to warfarin and aspirin, in VKA suitable and VKA unsuitable patients with AF, respectively.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cost-Benefit Analysis; Drug Costs; Factor Xa Inhibitors; Female; Hemorrhage; Hospitalization; Humans; Male; Markov Chains; Middle Aged; Multicenter Studies as Topic; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Antithrombins; Benzimidazoles; beta-Alanine; Contraindications; Dabigatran; Drug Substitution; Early Termination of Clinical Trials; Female; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Myocardial Infarction; Off-Label Use; Postoperative Complications; Pyridines; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Vitamin K

Preventing atrial fibrillation (AF) complications relies mainly on anticoagulant therapy. Still it is difficult to prescribe vitamin K antagonists (VKA) in geriatric patients with AF. In order to improve anticoagulation decision in this disease, we set up an algorithm. Charts of all patients with AF hospitalized between February and May 2012 were reviewed. Patients treated with anticoagulation for another indication (venous thromboembolism disease, prosthetic valve) were excluded. Algorithm was built-up with 6 criteria (past bleeding with VKA, autonomy (GIR score), MMSE score, risk of falls, co-morbidities index). Each criterion had a score (0, 0.5, 1 point) according to an intensity scale (light, moderate, high). The final algorithm composite score led to the prescription or not of VKA. Patients were followed-up during 6 months after discharge. One hundred and fifty-three patients were included, mean age 86.1 ± 5.6 years; 67.3% had a GIR score ≤3, 70.6% MMSE score < 23, and 83.7% a moderate risk of falls. According to the algorithm, 92 patients (60.1%) had a VKA prescription. Prescription was significantly less prescribed in the oldest old (p=0.02). Follow-up showed 4 bleeding events without any link with VKA prescription. Thirty-four patients died (22.2%), among 24 (34.4%) who did not have VKA (p=0.005). The algorithm improves VKA prescription according to an objective evaluation and probably prevents the prescription in the patients with the worse short term prognosis.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Risk Factors; Stroke; Vitamin K

Stroke prevention, achieved with oral anticoagulation therapy (OAT), is central to the management of patients with atrial fibrillation (AF). Well-managed OAT, as reflected by a long time in therapeutic range (TTR), is associated with good clinical outcomes. The SAME-TT2R2 score has been proposed to identify patients who will maintain a high average TTR on vitamin K antagonists (VKA) treatment. The objective of the study was to validate this score in a cohort of AF patients followed by an anticoagulation clinic. We applied the SAME-TT2R2 score to 1,089 patients with AF on VKAs followed by two anticoagulation clinics. The median TTR overall for the whole cohort was 73.0 %. There was a significant decline in mean (or median) TTR in relation to the SAME-TT2R2 score (p = 0.042). When the SAME-TT2R2 scores were categorized we find a TTR 74.0 % for score ≤2 and 68.0 % for score >2 (p = 0.006). The rate of major bleeding events and stroke/TIA was 1.78 × 100 patient-years (pt-yrs) and 1.26 × 100 pt-yrs, respectively. No relationship exists between the SAME-TT2R2 score and adverse events. We describe the first validation of the SAME-TT2R2 score in AF patients where, despite an overall good quality of anticoagulation, the SAME-TT2R2 score is able to identify the patients who are less likely to do well on VKA therapy if this is the chosen OAT.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Patient Selection; Prospective Studies; Stroke; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Biotin; Factor Xa Inhibitors; Female; Humans; Male; Oligosaccharides; Stroke; Thromboembolism; Vitamin K; Warfarin

The efficacy and safety of anticoagulation with use of vitamin K antagonists (VKAs) is highly dependent on the quality of anticoagulation control as reflected by the average time in a therapeutic range of 2.0 to 3.0. A clinical dilemma is trying to predict which anticoagulation-naive patients with atrial fibrillation (AF) would do well on a VKA (with a time in therapeutic range > 70%) and which are less likely to do well on a VKA but could be managed with novel oral anticoagulants.. The cohort comprised 8,120 patients, among whom 4,637 patients were receiving VKA. We investigated whether the SAMe-TT₂R₂ (sex female, age < 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled], race [doubled]) score could discriminate among patients with AF who were likely to have a labile international normalized ratio (INR) during follow-up as well as stroke/thromboembolism (TE), clinically relevant bleeding (defined as severe bleeding and as Bleeding Academic Research Consortium [BARC]-defined major bleeding), and death while being treated with a VKA.. During a mean follow-up of 1,016 ± 1,108 days, there was a significant increase in risk of severe bleeding events (risk ratio [RR], 1.38; 95% CI, 1.12-2.68; P = .002) and a significant increase in risk of major BARC bleeding (RR, 1.77; 95% CI, 1.29-2.44; P = .0005) in patients with AF with a high SAMe-TT₂R₂ score (> 2). Increasing SAMe-TT₂R₂ score was associated with an increasing risk of labile INR (P = .004), stroke/TE (P = .007), severe bleeding (P < .0001), major BARC bleeding (P < .0001), and death (P = .002) at follow-up. Among the patients taking VKAs, the SAMe-TT₂R₂ score was predictive of labile INR (C statistic approximately 0.58) as well as of stroke/TE, severe bleeding, major BARC bleeding, and death (C statistic, 0.54-0.57 for events), reflecting the suboptimal time in therapeutic range in such patients. This was not the case for patients who were not taking VKAs.. We demonstrate that the SAMe-TT₂R₂ score was predictive for an increasing risk of stroke/TE, severe bleeding, major BARC bleeding, and death, reflecting poor anticoagulation control (and labile INRs) among patients with AF given VKAs.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Cohort Studies; Comorbidity; Drug Interactions; Female; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Predictive Value of Tests; Racial Groups; Risk Assessment; Sex Factors; Stroke; Survival Rate; Tobacco Use; Treatment Outcome; Vitamin K

Essential information regarding efficacy and safety of vitamin K-antagonists (VKA) treatment for atrial fibrillation (AF) in non-dialysis dependent chronic kidney disease (CKD) is still lacking in current literature. The aim of our study was to compare the risks of stroke or transient ischemic attack (TIA) and major bleeds between patients without CKD (eGFR >60 ml/min), and those with moderate (eGFR 30-60 ml/min), or severe non-dialysis dependent CKD (eGFR <30 ml/min).. We included 300 patients without CKD, 294 with moderate, and 130 with severe non-dialysis dependent CKD, who were matched for age and sex. Uni- and multivariate Cox regression analyses were performed reporting hazard ratios (HRs) for the endpoint of stroke or TIA and the endpoint of major bleeds as crude values and adjusted for comorbidity and platelet-inhibitor use.. Overall, 6.2% (45/724, 1.7/100 patient years) of patients developed stroke or TIA and 15.6% (113/724, 4.8/100 patient years) a major bleeding event. Patients with severe CKD were at high risk of stroke or TIA and major bleeds during VKA treatment compared with those without renal impairment, HR 2.75 (95%CI 1.25-6.05) and 1.66 (95%CI 0.97-2.86), or with moderate CKD, HR 3.93(1.71-9.00) and 1.86 (95%CI 1.08-3.21), respectively. These risks were similar for patients without and with moderate CKD. Importantly, both less time spent within therapeutic range and high INR-variability were associated with increased risks of stroke or TIA and major bleeds in severe CKD patients.. VKA treatment for AF in patients with severe CKD has a poor safety and efficacy profile, likely related to suboptimal anticoagulation control. Our study findings stress the need for better tailored individualised anticoagulant treatment approaches for patients with AF and severe CKD.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Vitamin K

High vitamin K intake is associated with a reduced risk of coronary heart disease (CHD). This is thought to be mediated by increased activation of the vitamin K-dependent matrix γ-carboxyglutamate protein (MGP). Desphospho-uncarboxylated MGP (dp-ucMGP) is associated with both vitamin K status and vascular calcification. However, the association of dp-ucMGP with CHD and stroke in the general population has not been investigated to date.. To investigate the association of dp-ucMGP with incident CHD or stroke.. A prospective case-cohort study with a representative baseline sample of 1406 participants and 1154 and 380 incident cases of CHD and stroke, respectively, was nested within the EPIC-NL study. Circulating dp-ucMGP levels were measured with ELISA in baseline plasma samples. The incidence rates of fatal and non-fatal CHD and stroke were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs) per standard deviation (SD) and per quartile of circulating dp-ucMGP levels.. The average follow-up was 11.5 years. Levels of dp-ucMGP were not associated with CHD risk, with an HR per SD of 1.00 (95% confidence interval [CI] 0.93-1.07) and an HRQ4 vs. Q1 of 0.94 (95% CI 0.79-1.13) after adjustment for cardiovascular risk factors. There was no association of dp-ucMGP stroke risk (HRSD  0.98, 95% CI 0.90-1.08; and HRQ4 vs. Q1  1.09, 95% CI 0.78-1.51). This study could not confirm that high dp-ucMGP levels, reflecting poor vitamin K status, are associated with increased CHD or stroke risk in the general population.

Topics: Adult; Aged; Calcinosis; Calcium-Binding Proteins; Case-Control Studies; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Follow-Up Studies; Humans; Incidence; Male; Matrix Gla Protein; Middle Aged; Proportional Hazards Models; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease.. We examined 799 patients (mean age 65.1 ± 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho-carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK).. During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥ 977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32-2.72) and 1.88 (95% CI, 1.22-2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18-2.61) and 1.79 (95% CI, 1.12-2.57).. In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.

Topics: Aged; Biomarkers; Calcium-Binding Proteins; Cardiovascular Diseases; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Humans; Kaplan-Meier Estimate; Male; Matrix Gla Protein; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Proportional Hazards Models; Prospective Studies; Regression Analysis; Stroke; Treatment Outcome; Vascular Diseases; Vitamin K

Oral anticoagulation is highly effective in preventing stroke and mortality in nonvalvular atrial fibrillation patients. However, the efficacy and safety of vitamin K antagonists (the main oral anticoagulation drug used) strongly depends upon the quantity of anticoagulation control, as reflected by the average percentage of the time in therapeutic range of international normalized ratio 2.0-3.0. An easy, simple prediction of which atrial fibrillation patients are likely to do well on vitamin K antagonists (with good average time in therapeutic range) could guide decision-making between using vitamin K antagonists (eg, warfarin) and non-vitamin K antagonist oral anticoagulants.. In a consecutive cohort of nonvalvular atrial fibrillation patients attending our anticoagulation clinic, we tested the hypothesis that the new Sex, Race, Medical history, Tobacco use, Race (SAMe-TT2R2) score was a predictor for good average time in therapeutic range, and second, this would translate into adverse events in a "real world" cohort of patients with nonvalvular atrial fibrillation. The incidence of bleeding, adverse cardiovascular events (including stroke/thromboembolism), and mortality during the follow-up was higher with increasing SAMe-TT2R2 score. The SAMe-TT2R2 score was predictive for the composite of all adverse events (hazard ratio 1.32 [95% Confidence Interval 1.17-1.50]; P <.001), adverse cardiovascular events (1.52 [1.28-1.83]; P <.001), and all-cause mortality (1.41 [1.16-1.67]; P = .001). A trend was also observed for major bleeding events (1.23 [0.99-1.53]; P = .059).. In a "real world" cohort of consecutive patients with nonvalvular atrial fibrillation, a high SAMe-TT2R2 score (reflecting poor anticoagulation control with poor time in therapeutic range) was associated with more bleeding, adverse cardiovascular events, and mortality during follow-up.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Proportional Hazards Models; Racial Groups; Risk Assessment; Sex Factors; Stroke; Thromboembolism; Tobacco Use; Vitamin K

Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled trials on which their approval was based, and how their use has affected health spending for patients and insurers.. We used medical and prescription claims data from a large insurer to identify patients with nonvalvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin versus a novel anticoagulant.. There were 6893 patients with atrial fibrillation that initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income, and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (P <.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant.. This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Databases, Factual; Drug Utilization Review; Factor Xa Inhibitors; Fees, Pharmaceutical; Female; Humans; Income; Male; Middle Aged; Morpholines; Multivariate Analysis; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Severity of Illness Index; Sex Factors; Stroke; Thiophenes; United States; Vitamin K; Warfarin; Young Adult

Topics: Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Rivaroxaban; Stroke; Thiophenes; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Patient Selection; Stroke; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Biotin; Factor Xa Inhibitors; Female; Humans; Male; Oligosaccharides; Stroke; Thromboembolism; Vitamin K; Warfarin

Edoxaban recently proved non-inferior to warfarin for prevention of thromboembolism in patients with non-valvular atrial fibrillation (AF). We conducted an imputed-placebo analysis with estimates of the proportion of warfarin effect preserved by each non vitamin K antagonist oral anticoagulant (NOAC) and indirect comparisons between edoxaban and different NOACs.. We performed a literature search (up to January 2014), clinical trials registers, conference proceedings, and websites of regulatory agencies. We selected non-inferiority randomised controlled phase III trials of dabigatran, rivaroxaban, apixaban and edoxaban compared with adjusted-dose warfarin in non-valvular AF. Compared to imputed placebo, all NOACs reduced the risk of stroke (ORs between 0.24 and 0.42, all p<0.001) and all-cause mortality (ORs between 0.55 and 0.59, all p<0.05). Edoxaban 30 mg and 60 mg preserved 87% and 112%, respectively, of the protective effect of warfarin on stroke, and 133% and 121%, respectively, of the protective effect of warfarin on all-cause mortality. The risk of primary outcome (stroke/systemic embolism), all strokes and ischemic strokes was significantly higher with edoxaban 30 mg than dabigatran 150 mg and apixaban. There were no significant differences between edoxaban 60 mg and other NOACs for all efficacy outcomes except stroke, which was higher with edoxaban 60 mg than dabigatran 150 mg. The risk of major bleedings was lower with edoxaban 30 mg than any other NOAC, odds ratios (ORs) ranging between 0.45 and 0.67 (all p<0.001).. This study suggests that all NOACs preserve a substantial or even larger proportion of the protective warfarin effect on stroke and all-cause mortality. Edoxaban 30 mg is associated with a definitely lower risk of major bleedings than other NOACs. This is counterbalanced by a lower efficacy in the prevention of thromboembolism, although with a final benefit on all-cause mortality.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Meta-Analysis as Topic; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Vitamin K; Warfarin

Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs.. To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands.. Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER).. Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust.. In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.

Topics: 4-Hydroxycoumarins; Aged; Atrial Fibrillation; Cost of Illness; Cost-Benefit Analysis; Decision Support Techniques; Female; Fibrinolytic Agents; Humans; Indenes; Male; Netherlands; Pyrazoles; Pyridones; Stroke; Vitamin K

Topics: Antithrombins; Atrial Fibrillation; Embolism; Female; Humans; Male; Stroke; Vitamin K

Patients with atrial fibrillation are at increased risk for stroke and thus require anticoagulant prophylaxis with vitamin K antagonists. However, many such patients fail to achieve target coagulation status. The objective of this study was to evaluate time in the therapeutic range and its relationship to clinical outcomes in patients with nonvalvular atrial fibrillation prescribed a vitamin K antagonist in everyday clinical practice in 4 European countries (France, Germany, Italy and the United Kingdom).. Data were extracted from the European electronic primary care database, the Longitudinal Patient Database. Included in the analysis were 6250 adult patients for whom data on monitoring of coagulation time and international normalized ratio were available. The time within the therapeutic range was estimated by using the Rosendaal method. Patients spending >70% of time within the therapeutic range were considered to have well-controlled treatment. Data on stroke and bleeding events occurring during the study period were taken from patient records. Stroke risk was calculated by using the CHA2DS2-VASc score (i.e. 2 points for a history of stroke or TIA and age >75 years, and 1 point for age between 65 and 74 years, hypertension, diabetes mellitus, a recent cardiac failure, vascular disease and female sex).. The proportion of patients with poorly controlled treatment varied from 34.6% in the United Kingdom to 55.8% in Germany. The incidence of stroke was 0.5/100 person-years in well-controlled patients, compared with 1.0/100 in poorly controlled patients. After adjustment for stroke risk factors, the odds ratio was 1.38 (95% CI, 0.93-2.06; P = 0.110). The incidence of hemorrhage was 1.1 and 1.3 events/100 person-years, respectively (odds ratio, 0.91 [95% CI, 0.72-1.16]).. Many patients receiving prophylaxis with vitamin K antagonists in everyday community care have poorly controlled anticoagulation treatment with vitamin K antagonists. Their international normalized ratio is frequently outside the therapeutic range, and they are thus exposed to an unnecessary risk of stroke or bleeding complications.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Drug Monitoring; Female; Fibrinolytic Agents; France; Germany; Hemorrhage; Humans; Incidence; International Normalized Ratio; Italy; Male; Middle Aged; Risk Factors; Stroke; United Kingdom; Vitamin K; Whole Blood Coagulation Time; Young Adult

Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; District of Columbia; Drug Therapy, Combination; Humans; Insurance Coverage; Patient Compliance; Risk Assessment; Stroke; Vitamin K

Topics: Age Factors; American Heart Association; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiology; Factor Xa Inhibitors; Heart Rate; Humans; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Societies, Medical; Stroke; United States; Vitamin K

Topics: Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Stroke; Thiophenes; Vitamin K; Warfarin

The optimal approach to stroke prevention in geriatric patients with atrial fibrillation (AF) has not been adequately clarified. Despite their high risk of stroke and clear indication for anticoagulation according to established risk scores, in practice geriatric AF patients often are withheld treatment because of comorbidities and comedications, concerns about low treatment adherence or fear of bleeding events, in particular due to falls.. The present position paper summarises the outcomes of an expert panel discussion held by hospital-based and office-based physicians with ample experience in the treatment of geriatric patients.. The panel agreed that geriatric patients should receive oral anticoagulation as a rule, unless a comprehensive neurological and geriatric assessment (including clinical examination, gait tests and validated instruments such as Modified Rankin Scale, Mini-mental state examination or Timed Test of Money Counting) provides sound reasons for refraining from treatment AII patients with a history of falls should be thoroughly evaluated for further evaluation of the causes. Patients with CHADS2 score ≥ 2 should receive anticoagulation even if at high risk for falls. The novel oral anticoagulants (NOAC) facilitate management in the geriatric population with AF (no INR monitoring needed, easier bridging during interventions) and have an improved benefit-risk ratio compared to vitamin K antagonists. Drugs with predominantly non-renal elimination are safer in geriatric

Topics: Accidental Falls; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cooperative Behavior; Humans; Interdisciplinary Communication; Neurologic Examination; Neuropsychological Tests; Patient Care Team; Stroke; Treatment Outcome; Vitamin K

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

Dabigatran, rivaroxaban, and apixaban are the new oral anticoagulants (NOAC) which have been investigated in patients with atrial fibrillation (AF) for primary and secondary prevention of stroke and thromboembolism. In these trials NOAC had a similar efficacy and safety profile compared to traditional vitamin-K-antagonists such as warfarin. We advise caution in the use of NOAC in patients with stroke or cerebral hemorrhage because of the following reasons: 1) Patients with cerebral bleeding were excluded from the trials. 2) Stroke within 14 days and severe stroke within 6 months before screening were exclusion criteria in the trials investigating dabigatran and rivaroxaban. 3) There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. 4) NOAC are either substrates of the P-glycoprotein (P-gp) or are metabolized by the cytochrome P450 (CYP) system, or both. Drug-drug interactions between NOAC and P-gp and CYP-affecting drugs are largely unknown. 5) Long-term effects of thrombin generation inhibition on the occurrence of infections, malignancies, dementia, and other diseases are unknown. Based on these considerations it is our opinion that studies of NOAC in patients with stroke compared with other prevention strategies, as well as more post marketing surveillance data, are required.

Topics: Animals; Anticoagulants; Humans; International Normalized Ratio; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Stroke; Thrombin; Vitamin K

Atrial fibrillation is the most common form of cardiac arrhythmia with an age-dependent increase in prevalence. It is common clinical practice to treat patients with atrial fibrillation and who have a high risk for thromboembolic stroke with vitamin K antagonists. However, due to the many problems with vitamin K antagonist therapy many high risk patients are either not treated at all or receive insufficient anticoagulation treatment. The new oral anticoagulants, e.g. dabigatran as a direct thrombin antagonist or rivaroxaban and apixaban as factor Xa antagonists were tested in large scale clinical trials with respect to the efficacy in stroke prevention in atrial fibrillation patients. The therapeutic superiority over warfarin could be impressively proven either with respect to the efficacy in stroke prevention and/or to the safety of therapy with a significant decrease in cerebral bleeding complications.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Vitamin K

Intracerebral hemorrhage (ICH) is the most devastating complication of oral anticoagulation (OAC). As the number of patients on long-term OAC is expected to rise, the proportion of intracerebral hemorrhage related to OAC (OAC-ICH) in relation to spontaneous ICH (spont-ICH) is expected to increase as well. We determined the proportion of OAC-ICH in consecutive stroke patients and explored differences between OAC-ICH and spont-ICH regarding initial volume, hematoma expansion and outcome. Our prospective study consecutively enrolled patients with supra- and infratentorial ICH. The National Institute of Health Stroke Scale Score and the modified Rankin Scale (mRS) score at baseline and after 3 months, medical history and demographic variables were recorded. All admission and follow-up CTs/MRIs were analysed regarding ICH volume using the ABC/2-method. Intraventricular hemorrhage (IVH) was quantified using the Graeb score. Within 19 months, 2,282 patients were admitted to our ER. 206 ICH patients were included. Overall, 24.8 % of all ICH were related to OAC. Compared to patients with spont-ICH, OAC-ICH patients were older (p = 0.001), more frequently had initial extension of ICH into the ventricles (p = 0.05) or isolated primary IVH (p = 0.03) and a higher Graeb score upon admission (p = 0.01). In contrast, initial ICH volume (p = 0.16) and ICH expansion (p = 0.9) in those receiving follow-up imaging (n = 152) did not differ between the two groups. After correction for age, there was a trend towards poorer outcome in OAC-ICH (p = 0.08). One-fourth of all ICH are related to OAC. Initial extension of ICH into the ventricles and primary IVH are more frequent in OAC-ICH. The rate of hematoma expansion in OAC-ICH patients is similar to non-anticoagulated ICH patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Cohort Studies; Data Interpretation, Statistical; Disease Progression; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Neurologic Examination; Prospective Studies; Stroke; Treatment Outcome; Vitamin K; Warfarin

Oral anticoagulants block the coagulation cascade either by an indirect mechanism (e.g., vitamin K antagonists) or by a direct one (e.g., the novel oral anticoagulants). Vitamin K antagonists are widely used as treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. Although low molecular weight heparin remains the first line in venous thromboembolism prophylaxis, more recently the novel oral anticoagulants such as dabigatran (initial dose of 110 mg within 1-4 h after surgery, followed by the full dose of 220 mg once daily), rivaroxaban (dose of 10 mg once daily, with the first dose administered 6-10 h after the surgery), and apixaban (dose of 2.5 mg twice daily, starting 12-24 h after surgery, but available only in Europe) are approved for prophylaxis in patients undergoing major orthopedic surgery. The period in which thromboembolic risk abates remains uncertain, and trials of extended therapy are still ongoing. After showing at least noninferiority to warfarin in RE-LY, ROCKET-AF, and ARISTOTLE trials, dabigatran (110 or 150 mg twice daily), rivaroxaban (20 or 15 mg once daily), and apixaban (5 mg twice daily), respectively, were approved also for stroke prevention in patients with atrial fibrillation. While awaiting long-term safety data, the choice among all these available therapies should be based on patient preferences, compliance, and ease of administration, as well as on local factors affecting cost-effectiveness.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Humans; Morpholines; Orthopedic Procedures; Practice Guidelines as Topic; Prognosis; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K

Oral anticoagulants offer the best long-term protection against ischemic stroke in patients with atrial fibrillation (AF). However, vitamin K antagonists (VKA) are cumbersome to use and their prescription is far from guidelines recommendations. We report the results of a large survey on the attitudes of prescription of VKA in patients with AF.. 7148 patients were enrolled by 196 Internal Medicine (MED) and 164 Cardiology (CARD) centers, and VKA specifically analyzed. Thrombotic and hemorrhagic risks were evaluated by means of CHADS2 and CHA2DS2VASc scores, and a study-specific bleeding score (modified HAS-BLED).. 63.9% of non-valvular patients had a CHADS2 score≥2 (MED: 75.3%-CARD: 53.1%), and 28.4% a bleeding score≥3 (41.9% MED-15.8% CARD). VKA were prescribed in 55.5% of non-valvular patients (46.3% MED and 64.2% CARD), in 81% of high-risk valvular patients and in 58.8% of the overall study population. Among patients at high risk of bleeding (score≥3), VKA were prescribed in 26.9% of subjects, while, in the subgroup at high risk of thrombosis (CHADS2 Score<2), these were prescribed in 54.4%. Age≥75, paroxysmal AF, cognitive impairment, need for assistance, CHADS2<2 and bleeding score≥3 were independent predictors of non-use of VKA.. Oral anticoagulants are more frequently used in CARD than in MED, plausibly due to greater complexity of MED patients. Stratification of thrombotic and hemorrhagic risk significantly drives the choice for VKA. However the fraction of patients in whom prescription or non-prescription is based on other individual characteristics is not negligible.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Decision Support Techniques; Female; Humans; Inappropriate Prescribing; Male; Multivariate Analysis; Practice Patterns, Physicians'; Risk Assessment; Stroke; Vitamin K

Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated.. The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults (≥18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with ≥1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean±SD CHADS2 score was 1.9±1.2, and 57.2% had a score ≥2. Mean CHA2DS2-VASc score was 3.2±1.6, and 8,957 (84.4%) had a score ≥2. Overall, 38.0% of patients with a CHADS2 score ≥2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy.. These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.. ClinicalTrials.gov TRI08888.

Topics: Aged; Atrial Fibrillation; Contraindications; Female; Fibrinolytic Agents; Humans; Male; Molecular Sequence Data; Prospective Studies; Randomized Controlled Trials as Topic; Registries; Risk Factors; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Humans; International Normalized Ratio; Stroke; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Drug Substitution; Humans; International Normalized Ratio; Practice Guidelines as Topic; Stroke; Vitamin K; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Blood Pressure; Humans; Research Design; Stroke; Thromboembolism; Vitamin K

Topics: Atrial Fibrillation; Embolism; Factor Xa; Female; Humans; Male; Morpholines; Stroke; Thiophenes; Vitamin K

Topics: Atrial Fibrillation; Embolism; Factor Xa; Female; Humans; Male; Morpholines; Stroke; Thiophenes; Vitamin K

Atrial fibrillation is the most common cause of embolic stroke associated to heart disease. Oral anticoagulation with vitamin K antagonists substantially reduces this risk.. We assessed a group of patients with prior diagnosis of atrial fibrillation who sustained an ischemic stroke while receiving an adequate regime of oral anticoagulation.. We evaluated consecutive patients with ischemic stroke and prior diagnosis of atrial fibrillation. We determined demographics, clinical characteristics, TOAST stroke subtypes, CHADS2 scores, and prior or concomitant use of oral anticoagulants.. We studied 112 patients. Thirty nine of them (35%) had received an adequate dose of a vitamin K antagonist during the 24-hour period preceding the stroke. There were no differences in demographics, vascular risk factors, CHADS2 scores, nor medications use between patients who were or were not receiving anticoagulation. Other potential etiologies for stroke occurrence were found in 8 (21%) anticoagulated patients, and in 3 (4%) non-anticoagulated subjects (p<0.01). Anticoagulated patients had a mean international normalized ratio (INR) of 2.3 ± 1.3 (median 2.05), and INR was within therapeutic ranges (i.e., ≥ 2) in 54% of these subjects.. A substantial proportion of patients with atrial fibrillation who have an ischemic stroke are already receiving oral anticoagulation. Sub-optimal levels of anticoagulation and additional etiologies explain, only in part, this failure. Further research is needed to help find adequate therapeutic strategies in atrial fibrillation patients who sustain an ischemic stroke while receiving oral anticoagulation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; International Normalized Ratio; Male; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Meta-Analysis as Topic; Stroke; Vitamin K

To estimate the prevalence of atrial fibrillation among Greenlanders with ischemic stroke.. A cross-sectional study.. Information on atrial fibrillation and vitamin K antagonistic treatment at admittance and at discharge was obtained for Greenlanders admitted to Queen Ingrid's Hospital in Nuuk with an ischemic stroke in 2011 or in 2012 with methods described in details elsewhere.. Of 139 patients (64 males and 75 females) Greenlanders with an ischemic stroke in 2011 (n=74) or 2012 (n=65), 5.0% (n=7) had known atrial fibrillation prior to stroke compared to 32.4% (n=45) after discharge (p<0.01).. More than 30% of ischemic stroke patients in this study had atrial fibrillation and only 5% were diagnosed prior to the stroke, suggesting that unknown atrial fibrillation is a substantial risk factor of ischemic stroke among Greenlanders.

Topics: Aged; Atrial Fibrillation; Comorbidity; Cross-Sectional Studies; Female; Greenland; Humans; Male; Middle Aged; Prevalence; Risk Factors; Stroke; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Drug Approval; Drugs, Investigational; Education, Medical; Education, Medical, Continuing; France; Geriatric Psychiatry; Humans; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Male; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Male; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Male; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Male; Stroke; Vitamin K

The prevalence of AF is higher in men and increases with age. However, the number of elderly women is higher than that of elderly men, and AF should be considered to affect men and women equally. Little information exists on elderly AF patients, and in particular, whether stroke and bleeding risk differs between elderly women and elderly men remains unknown.. We have performed the EPICA Study, a large, multicentre observational study including 4093 elderly patients who started VKA treatment after the age of 80years. In this study, we will focus our analysis on 3015 AF patients followed for 7620 patient-years (pt-yrs) to evaluate if bleeding and stroke risks were different between genders.. During follow-up, we recorded 112 ischemic cerebral events (rate 1.5 ×100pt-years) with no difference between genders. History of previous stroke/TIA, hypertension and artery vascular disease are independently associated with stroke/TIA during treatment. We recorded 132 major bleeds (rate 1.7 ×100pt-years); males showed a higher risk of bleeding (OR 1.5), even if not statistically significant. At multivariate analysis, history of major bleeds, history of falls and active cancer are risk factors independently associated to bleeding.. Elderly patients with AF do not show clear gender related differences in the risk of major adverse events. However, elderly males showed a higher rate of bleeding complications, and females showed a slightly higher rate of stroke, thus suggesting the possibility of a higher net clinical benefit of anticoagulant treatment in females.

Topics: Age Factors; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Hemorrhage; Humans; Italy; Male; Multivariate Analysis; Odds Ratio; Proportional Hazards Models; Risk Assessment; Risk Factors; Sex Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K

Atrial fibrillation is a major risk factor for ischemic stroke and anticoagulation therapy is indicated to reduce risk. Dabigatran is a new oral anticoagulant that does not require INR monitoring. This study evaluated the cost-effectiveness of dabigatran versus vitamin K antagonists for stroke prevention in atrial fibrillation in Switzerland.. A Markov model simulating the course of treatment and occurrence of clinical events in two treatment arms over the lifetime of patients was adapted to the Swiss context. The adaptation included the cost of anticoagulation therapy and clinical events in Switzerland. The cost of inpatient care was estimated on data of all inpatient hospital stays in 2008. The calculation of outpatient care costs was based on peer reviewed studies, expert interviews and local tariffs.. Patients treated with dabigatran had a higher life expectancy and experienced more quality adjusted life years (QALY) while incurring higher costs than patients treated with vitamin K antagonists. The estimated incremental cost-effectiveness ratio (ICER) was CHF 25,108.‒ per QALY with 110 mg and CHF 9,702 per QALY with 150 mg of dabigatran. A sequential dosage scheme, in which 150 mg are administered up to the age of 80 years and 110 mg thereafter, resulted in an ICER of CHF 10,215 per QALY. A sensitivity analysis confirmed that these results are robust.. Dabigatran can be considered cost-effective in comparison with vitamin K antagonists in the Swiss context. The higher drug cost of dabigatran is compensated by savings in INR monitoring, lower cost of clinical events and QALY-gains.

Topics: Aged; Antifibrinolytic Agents; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Dose-Response Relationship, Drug; Female; Humans; Male; Markov Chains; Middle Aged; Models, Econometric; Quality of Life; Quality-Adjusted Life Years; Stroke; Switzerland; Vitamin K

Topics: Atrial Fibrillation; Embolism; Factor Xa; Female; Humans; Male; Morpholines; Rivaroxaban; Stroke; Thiophenes; Vitamin K

Vitamin K antagonists (VKA) are highly recommended in patients with atrial fibrillation for their efficacy in preventing stroke. However, there is a lack of data on oral anticoagulation (OAC) with VKA overall treatment (i.e. from writing the prescription to time spent in therapeutic range) in patients discharged from hospital with a diagnosis of atrial fibrillation.. The aim of this study was to assess the adherence to stroke prevention guidelines in a cohort of patients discharged with atrial fibrillation from the two hospitals of the Agency for Health Services no. 3 'Upper Friuli'.. All patients discharged from the hospitals with a diagnosis of nonvalvular atrial fibrillation during the year 2009 were enrolled in this study. Record linkage for the previous 5 years and pharmaceutical data were used to assess comorbid conditions (ICD9-CM) and to calculate congestive heart failure, hypertension, age at least 75 years, diabetes and stroke (CHADS2) scores. Prescription orders were obtained from discharge letters. Patients' adherence to VKA prescription was assessed through pharmacy records, and prothrombin/international normalized ratios (INR) for a period of 180 days after discharge from the whole 'Upper Friuli' laboratories. A patient was considered to have purchased VKA if at least one drug purchase was found in the pharmacy records. Time in therapeutic range (TTR) was calculated in patients who had at least two INR measurements.. In 2009, 509 patients (mean age 80 ± 8 years) were discharged with atrial fibrillation from 'Upper Friuli' hospitals (90% from internal medicine); of these, 284 patients (55.8%) had a CHADS2 score greater than 1 and no contraindications to VKA therapy at discharge. Within this subgroup, 112 patients (39.4%) received VKA prescription at discharge; of these, 84 (29.6%) purchased VKA and 58 patients had a TTR of at least 65% (20.4%).. VKA prescription for atrial fibrillation patients is low and not explained by present or past comorbid condition. A second failure is represented by patients' low compliance. Overall, adherence to VKA guidelines in atrial fibrillation is scarce.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Prescriptions; Follow-Up Studies; Guideline Adherence; Hospitals; Humans; Italy; Medication Adherence; Middle Aged; Patient Discharge; Risk Assessment; Stroke; Time Factors; Vitamin K

Topics: Anticoagulants; Humans; Intracranial Hemorrhages; Risk Factors; Secondary Prevention; Stroke; Vitamin K

The management of antithrombotic therapy after intracerebral hemorrhage (ICH) in anticoagulated patients is not well defined. We analyzed the risks and benefits of antiplatelet therapy (AG) against the resumption of anticoagulation with vitamin K antagonists (AVK) in a series of patients.. Retrospective study of ICH in anticoagulated patients. We registered demographic data, history of hypertension (HT), time of follow-up and new cerebral vascular events (ICH, stroke [IC]).. We evaluated 88 patients, mean age 69±9 years, 50% men, 73% hypertensive. During the acute phase 18 patients died and the follow-up was lost in 31. Of the remaining (n=39), AVKs were resumed in 25 and changed to AG in 14. Comparing the characteristics of both groups, the anticoagulated group was younger (P=.005) and the embolic sources were more often of higher risk (P=.003). After an average follow-up of 54±31 months, the distribution of events was: IC (AVKs 8%, AG 14.3%, P=.6), ICH (AVKs 24%, AG 7.1%, P=.38), IC or ICH (AVKs 32%, AG 21.4%, P=.48) and death (AVKs 29%, AG 7.1%, P=.21). This trend of increased risk of new events in patients with AVKs was confirmed by Kaplan-Meier curves, although without statistical differences.. Restarting AVK treatment after ICH in anticoagulated patients could increase the risk of new bleeding events and mortality. Prospective studies are needed to define a better and appropriate antithrombotic therapy after ICH related with anticoagulation.

Topics: Aged; Anticoagulants; Aspirin; Cerebral Hemorrhage; Clopidogrel; Female; Follow-Up Studies; Humans; Intracranial Embolism; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Retrospective Studies; Risk; Risk Factors; Stroke; Ticlopidine; Vitamin K

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Vitamin K

The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios.. We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement.. For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy.. Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Atrial Flutter; Benzimidazoles; beta-Alanine; Clopidogrel; Dabigatran; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electric Countershock; Evidence-Based Medicine; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Risk Factors; Societies, Medical; Stroke; Ticlopidine; Vitamin K

Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered.. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.. In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C).. These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Topics: Aspirin; Catheterization; Combined Modality Therapy; Ductus Arteriosus, Patent; Evidence-Based Medicine; Fibrinolytic Agents; Heart Atria; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Mitral Valve; Platelet Aggregation Inhibitors; Postoperative Complications; Rheumatic Heart Disease; Risk Factors; Societies, Medical; Stroke; Thromboembolism; Thrombolytic Therapy; Thrombosis; Vitamin K

Vitamin K antagonists (VKA) therapy is increasingly used in elderly for prevention of venous thromboembolism (VTE) and of stroke in atrial fibrillation (AF). Glomerular filtration rate (GFR), usually estimated from different equations, decreases progressively with age and it is a risk factor for bleeding. In the frame of the EPICA study, a multicentre prospective observational study including 4,093 patients ≥80 years naïve to VKA treated for AF or after VTE, we performed this ancillary study to evaluate the prevalence of chronic kidney diseases (CKD) by estimated GFR (eGFR). Incidence of bleedings was recorded and bleeding risk was evaluated in relation to eGFR calculated by Cockroft-Gault (C-G); Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. In addition, the agreement among the three eGFR formulas was evaluated. We recorded 179 major bleedings (rate 1.87 x100 patient-years [py]), 26 fatal (rate 0.27 x100 py). Moderate CKD was detected in 69.3%, 59.3% and 47.0% and severe CKD in 5.8%, 7.4% and 10.0% of cases by C-G, MDRD and CKD-EPI, respectively. Bleeding risk was higher in patients with severe CKD irrespective of the applied equation. This study confirms that CKD represents an independent risk factor for bleeding and that a wide proportion of elderly on VKA had severe or moderate CKD, suggesting the need for frequent monitoring. Although the different available equations yield different eGFR, all appear to similarly predict the risk of major bleeding.

Topics: Age Factors; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chronic Disease; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Incidence; Italy; Kidney; Kidney Diseases; Male; Odds Ratio; Prevalence; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Treatment Outcome; Venous Thromboembolism; Vitamin K

As a potential alternative to long-term oral anticoagulation with vitamin K antagonists in patients with atrial fibrillation, the interventional left atrial appendage occlusion has shown to be non-inferior regarding neurological events. With the new oral direct factor II and factor Xa inhibitors playing an emerging role in stroke prophylaxis, an individual treatment strategy has to be found weighing bleeding and stroke risk against the peri-interventional complication rate based on established risk scores.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Evidence-Based Medicine; Humans; Stroke; Vitamin K

Two novel oral anticoagulants, namely the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitor rivaroxaban, have recently been approved for treatment of atrial fibrillation. They differ in many ways from vitamin K antagonists, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of a need for monitoring and no need for titration or dose adjustments. Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. Ideally these anticoagulant agents would be assessable using a sensitive and standardized test with a linear dose-response curve. Optimized assays are currently under investigation and may quantify the anticoagulant effect. At present the therapeutic ranges for dose adjustment have not yet been established.

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

The standardized and constant fixed-dose rate, no necessity for a close and regular blood monitoring as well as the small number of interactions with other drugs and daily food make therapy with the new oral anticoagulants dabigatran and rivaroxaban and in future presumably apixaban much easier and more feasible than the standard therapy with vitamin K antagonists (VKA). In summary the trials focusing on patients with non-valvular atrial fibrillation show that the new substances are at least non-inferior or even coequal to the well-known VKAs regarding prevention of thromboembolism. In addition the risk of fatal and especially intracranial hemorrhage can be considered even lower. Furthermore, the trials indicate a trend in reduction of death from any cause in treating these patients with the new drugs. There was no inferiority or even superiority in patient-outcome in extended prevention of venous thrombosis and pulmonary embolism after knee or hip arthroplasty when treating patients with the new substances by oral administration versus subcutaneous administration of low molecular weight heparin. Comparable results were demonstrated in the therapy of patients with acute deep vein thrombosis compared with the standard therapy of low molecular weight heparin and VKAs while there was a similar safety profile. Concerning the specific treatment of coronary heart disease and a combined antiplatelet therapy, profound data are still missing. The lack of specific antidotes the as yet limited experience with these substances over a longer period of time and last but not least the emerging costs have inhibited a broad use of these new agents up until now.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Evidence-Based Medicine; Humans; Stroke; Vitamin K

New oral anticoagulants, such as dabigatran, rivaroxaban, apixaban, and edoxaban display pharmacologic and pharmacodynamic data similar to low molecular weight heparins. Peak levels are found 2-4 h after oral ingestion and elimination half-lives are in the range of 7-14 h. The drugs differ primarily concerning renal elimination. Dose adjustment is only performed in patients with impaired renal function, high risk of bleeding and patients with co-medications which influence the metabolism or anticoagulant effect of the drugs. Due to the short half-life, perioperative bridging is not necessary. Currently, no specific antidotes are available: however, assay systems are available for measuring the plasma concentration of dabigatran and rivaroxaban. In emergency cases a normal thrombin time excludes relevant levels of dabigatran, whereas a normal anti-factor Xa assay result excludes relevant levels of factor Xa inhibitors.The new anticoagulants are being used for prophylaxis of venous thrombosis in elective hip and knee surgery, as well as for treatment of venous thrombosis and for prevention of stroke and systemic embolism in patients with atrial fibrillation. Additional indications are to follow. Dabigatran is given at a dose of 110 mg initially 1-4 h after surgery followed by 220 mg once daily for prophylaxis of thrombosis and at doses of 110 mg or 150 mg twice daily for therapeutic anticoagulation. The prophylactic and therapeutic doses of rivaroxaban are 10 and 20 mg and, of apixaban 2.5 mg and 5 mg twice daily, respectively.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Humans; Stroke; Thrombosis; Vitamin K

An effective oral anticoagulation with vitamin K antagonists is currently a successfully used standard therapy in patients with atrial fibrillation (AF) yielding a 60-70% relative reduction in stroke risk compared with placebo, when an international normalized ratio (INR) value between 2.0 and 3.0 is maintained. However, these agents have a number of well documented shortcomings which partially result in a reduced compliance as well as an insufficient INR adjustment. A number of new drugs for oral anticoagulation including direct factor Xa inhibitors, such as rivaroxaban and direct thrombin inhibitors, such as dabigatran have shown promising results, including higher efficacy and significantly lower incidences of intracranial bleeding compared with warfarin. The new substances show similar results in secondary as well as in primary stroke prevention in patients with AF and therefore offer a number of advantages over warfarin, including a favorable bleeding profile and convenience of use. Consideration of these new anticoagulants might be a good option.

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

Topics: Anticoagulants; Atrial Fibrillation; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Kidney Diseases; Male; Stroke; Venous Thromboembolism; Vitamin K

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

About 40% of patients who receive oral anticoagulation would not start treatment with vitamin K antagonists due to the regular control they require and their interference with the diet and other concomitant medications.. To analyze the preferences of patients with non valvular atrial fibrillation for oral anticoagulants (OAs) for the stroke prevention.. Observational, multicentric study on preferences and maximum willingness to pay based on conjoint analysis: literature review, focus groups and semi-structured interviews with physicians and patients (n = 295) to define the attributes of OAs and their levels. Definition of scenarios that patients ordered according to their preferences. Clusters analysis to identify population groups by their preferences.. Eight scenarios were defined based on five attributes: efficacy, security, a fixed dose, need for coagulation controls and interactions with diet and medication. The most preferred attribute was the smaller number of embolisms in a year (importance: 30.15%) followed by the fixed dose of the OA (25.45%) and the smaller number of intracranial hemorrhage in a year (21.57%). Three clusters population were identified. The maximum amount patients' were willingness to pay for the OA was 66.76 ± 54.64 euros (mean) per month.. Efficacy and a fixed dose are the attributes of OA most valued by non valvular atrial fibrillation patients. There are groups of patients who differ in their preferences. This differences should be taken into account when deciding instauration or change on the OA treatment to ameliorate the accomplishment and prevention in this patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Drug Interactions; Factor Xa Inhibitors; Food-Drug Interactions; Humans; Medication Adherence; Middle Aged; Patient Preference; Prescription Fees; Stroke; Thrombophilia; Time Factors; Vitamin K

Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment.. Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90-360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40).. High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Comorbidity; Denmark; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Registries; Risk Factors; Stroke; Ticlopidine; Vitamin K

Assessment of the cost-effectiveness of dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in Spain, from the perspective of the National Health System.. Adaptation of a Markov chain model that simulates the natural history of the disease over the lifetime of a cohort of 10,000 patients with non-valvular atrial fibrillation. Model comparators were warfarin in a first scenario, and a real world prescribing pattern in a second scenario, in which 60% of the patients were treated with vitamin K antagonists, 30% with acetylsalicylic acid, and 10% received no treatment. Deterministic and probabilistic sensitivity analyses were performed.. Dabigatran reduced the occurrence of clinical events in both scenarios, providing gains in quantity and quality of life. The incremental cost-effectiveness ratio for dabigatran compared to warfarin was 17,581 euros/quality-adjusted life year gained and 14,118 euros/quality-adjusted life year gained when compared to the real world prescribing pattern. Efficiency in subgroups was demonstrated. When the social costs were incorporated into the analysis, dabigatran was found to be a dominant strategy (ie, more effective and less costly). The model proved to be robust.. From the perspective of the Spanish National Health System, dabigatran is an efficient strategy for the prevention of stroke in patients with non-valvular atrial fibrillation compared to warfarin and to the real-world prescribing pattern; incremental cost-effectiveness ratios were below the 30,000 euros/quality-adjusted life year threshold in both scenarios. Dabigatran would also be a dominant strategy from the societal perspective, providing society with a more effective therapy at a lower cost compared to the other 2 alternatives. Full English text available from:www.revespcardiol.org.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Embolism; Female; Humans; Male; Markov Chains; Spain; Stroke; Vitamin K; Warfarin

Topics: Amiodarone; Anticoagulants; Atrial Fibrillation; Dronedarone; Germany; Humans; Long-Term Care; Practice Guidelines as Topic; Risk Assessment; Stroke; Thromboembolism; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Health Services Accessibility; Humans; Inappropriate Prescribing; Practice Guidelines as Topic; Registries; South Africa; Stroke; Vitamin K

We investigated whether CHADS2 or CHA2DS2-VASc scores could be used to predict 1-year prognosis in stroke recurrence, mortality, and mortality of ischemic stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF).. Patients were selected from a national prospective registry in China. The clinical prediction of the scores was examined using the C statistic. Univariate and multivariate logistic regressions were performed to analyze the relevant risk factors.. Thousand two hundred and ninety-seven of 22,216 patients were enrolled in the study. For stroke recurrence rate, the C statistic value was 0.53 (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.01 to 1.32) for CHADS2 and 0.55 (OR 1.14, 95% CI: 1.05 to 1.24) for CHA2DS2-VASc; adding baseline National Institutes of Health Stroke Scale (NIHSS) score to these two scores, the value of C statistic was 0.58 (OR 1.25 95% CI: 1.14 to 1.37) and 0.58 (OR 1.19, 95% CI: 1.11 to 1.27), respectively.. Both CHADS2 and CHA2DS2-VASc scores have limitations in predicting the 1-year prognosis of stroke/TIA patients with NVAF in China. The predictive value of these two scores improved by adding the baseline NIHSS score.

Topics: Aged; Aged, 80 and over; Area Under Curve; Atrial Fibrillation; China; Female; Follow-Up Studies; Humans; Ischemic Attack, Transient; Logistic Models; Male; Predictive Value of Tests; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Self Report; Severity of Illness Index; Stroke; Survival Rate; Vitamin K

New oral anticoagulants are already or will be soon available. They have shown good efficacy and safety in various studies (prevention and treatment of venous thromboembolism, atrial fibrillation). Their arrival will probably modify the prescription of the current anticoagulant agents. However some precaution should be given in their use pending post marketing studies. Although these new drugs are intended to replace mostly vitamin K antagonists, a place will remain for "old" anticoagulants during the next years.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Evidence-Based Medicine; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Atrial fibrillation (AF) is the most prevalent arrhythmia in man. Incidence increases with age, risk of ischemic stroke as a result of AF disproportionally so. Anticoagulation is therefore one of the cornerstones of treatment. Perceived severity of bleeding risk on anticoagulants is, however, one of the main reasons that the elderly population at highest risk is relatively undertreated.This article describes both risks for the traditional vitamin K antagonists,in addition to the new direct thrombin and factor Xa antagonists.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Incidence; Male; Stroke; Thrombin; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke; Vitamin K

Systemic thromboembolism is a severe complication in patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Vitamin K antagonists greatly reduce the risk of thromboembolic events, but the administration scheme before ECV is troublesome as difficulties in reaching and maintaining the target therapeutic range for 3 weeks often delay the restoration and likelihood of maintaining sinus rhythm. Low molecular weight heparins (LMWHs) do not need dose adjustment, and may be preferable in this clinical setting. In this multicentre study, the LMWH parnaparin was used at a dose of 85 anti-factor Xa U/kg b.i.d. 2 weeks before and 3 weeks after ECV of AF. In an intention to treat analysis of 102 patients, there was no systemic thromboembolism or major bleeding (0%, 95% CI 0-3.6). Two clinically relevant non-major bleeds (2.5%, 95% CI 0.7-8.8) and three minor bleeds (3.8%, 95% CI 1.3-10.6) were recorded. No heparin-induced thrombocytopenia or other major adverse events were recorded. Parnaparin appears effective and safe for thromboprophylaxis of elective ECV in patients with AF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Confidence Intervals; Electric Countershock; Female; Heparin, Low-Molecular-Weight; Humans; Male; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Vitamin K

Although currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low molecular weight heparin and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa. The new agents produce such a predictable anticoagulant response that they can be given in fixed doses without monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drug Discovery; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombin; Venous Thromboembolism; Vitamin K

To report a case of a critically elevated international normalized ratio (INR) following discontinuation of a vitamin K supplement in a patient receiving warfarin.. A 64-year-old man with atrial fibrillation received warfarin for primary stroke prevention. He was initiated on low-dose vitamin K supplementation therapy secondary to a high level of INR variability. The patient was stabilized on this therapy for approximately 9 months with a mean INR of 2.02 and a warfarin dose ranging from 6.5 to 7.5 mg/week. At a visit with his primary care physician, the patient's INR was subtherapeutic at 1.5. He had not been taking his vitamin K supplement for nearly a week, but had not missed any doses of warfarin. The vitamin K supplement was discontinued and his warfarin dose was increased by 14.3%. Nearly 2 weeks later the patient presented with a critically elevated INR of 8.5, but no acute bleeding. No other factors affecting the INR could be determined. After a dose of 2.5 mg of vitamin K was administered and warfarin was withheld for 2 days, the patient's INR returned to 2.9. Low-dose vitamin K supplementation and warfarin at a lower dose of 7 mg/week were restarted. His INR remained relatively stable, with no ensuing critical INR changes or other sequelae.. Vitamin K supplement removal was believed to be a major contributor to the critically elevated INR. While the warfarin dose had been increased according to the clinic protocol (14.3% for an INR of 1.5), the timing of the INR elevation following supplement removal follows pharmacodynamic expectations of clotting factor synthesis. This case is labeled a category D error.. Discontinuation of vitamin K supplementation therapy might result in elevation of INR.

Topics: Anticoagulants; Atrial Fibrillation; Dietary Supplements; Drug Interactions; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Risk Factors; Stroke; Vitamin K; Warfarin

To evaluate the individual risk factors composing the CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score and the CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism.. Registry based cohort study.. Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006.. Stroke and thromboembolism.. Of 121,280 patients with non-valvular atrial fibrillation, 73,538 (60.6%) fulfilled the study inclusion criteria. In patients at "low risk" (score = 0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS(2) and 0.78 (0.58 to 1.04) with CHA(2)DS(2)-VASc at one year's follow-up. In patients at "intermediate risk" (score = 1), this rate was 4.75 (4.45 to 5.07) with CHADS(2) and 2.01 (1.70 to 2.36) with CHA(2)DS(2)-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years' follow-up were 0.812 (0.796 to 0.827) with CHADS(2) and 0.888 (0.875 to 0.900) with CHA(2)DS(2)-VASc.. The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA(2)DS(2)-VASc performed better than CHADS(2) in predicting patients at high risk, and those categorised as low risk by CHA(2)DS(2)-VASc were truly at low risk for thromboembolism.

Topics: Aged; Atrial Fibrillation; Female; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Risk Assessment; Stroke; Thromboembolism; Vitamin K

Patients with atrial fibrillation (AF) at risk of stroke are not always anticoagulated with vitamin K antagonists (VKA) despite lack of contraindication. Dabigatran, an oral direct thrombin inhibitor, is a new option with proven safety and effectiveness in these patients. The advantages of dabigatran are its more predictable response, obviating coagulation monitoring and possible lower frequency of bleedings. Its drawbacks are cost, lack of antidote and long-term data, frequency of dyspepsia and the twice daily dosage.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Risk Assessment; Stroke; Vitamin K

All stroke risk stratification schemes categorize a history of stroke as a "truly high" risk factor. Therefore, stratifying stroke risk in atrial fibrillation (AF) should perhaps concentrate on primary prevention. However, the risk factors for stroke also lead to an increase in the risk of bleeding. Our objective was to evaluate the agreement among the currently used stroke risk stratification schemes in "real-world" patients with AF in the primary prevention setting, their correlation with adverse events recorded during warfarin treatment, and the relationship between stroke and bleeding risk.. We prospectively followed up 3,302 patients with AF taking warfarin for primary prevention. Stroke risk was assessed using the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke or transient ischemic attack), Atrial Fibrillation Investigators, American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy, American College of Cardiology/American Heart Association/European Society of Cardiology, and National Institute for Health and Clinical Excellence schemas, and for bleeding risk, the outpatient bleeding risk index was calculated. Bleeding and thrombotic events occurring during follow-up were recorded.. Patients classified into various stroke risk categories differed widely for different schemes, especially for the moderate- and high-risk categories. The rates of bleeding and thrombotic events during follow-up were 1.24 and 0.76 per 100 patient-years, respectively. All stroke stratification schemes correlated closely to bleeding risk. Stroke rate increased progressively from low- to moderate- to high-risk patients.. Stroke risk stratification models differed widely when categorizing subjects into the moderate- and high-stroke-risk categories. Bleeding and stroke risk were closely correlated and both were low among low-risk patients and were similarly high among moderate/high-risk groups.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Primary Prevention; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Vitamin K; Warfarin

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Evidence-Based Medicine; Fibrinolytic Agents; Germany; Hemorrhage; Humans; International Normalized Ratio; Practice Guidelines as Topic; Risk Assessment; Stroke; Thromboembolism; Vitamin K

Vitamin K antagonists (VKA) are currently the most frequently used drug to prevent ischaemic stroke in atrial fibrillation (AF) patients. However, VKA use has been associated with increased vascular calcification. The aim of this study was to investigate the contribution of VKA use to coronary artery calcification in low-risk AF patients.. A prospective coronary calcium scan was performed in 157 AF patients without significant cardiovascular disease (108 males; mean age 57 ± 9 years). A total of 71 (45%) patients were chronic VKA users. The duration of VKA treatment varied between 6 and 143 months (mean 46 months). No significant differences in clinical characteristics were found between patients on VKA treatment and non-anticoagulated patients. However, median coronary artery calcium scores differed significantly between patients without and patients with VKA treatment [0, inter-quartile range (IQR) 0-40, vs. 29, IQR 0-184; P = 0.001]. Mean coronary calcium scores increased with the duration of VKA use (no VKA: 53 ± 115, 6-60 months on VKA: 90 ± 167, and >60 months on VKA: 236 ± 278; P < 0.001). Multivariable logistic regression analysis revealed that age and VKA treatment were significantly related to increased coronary calcium score.. Patients using VKA show increased levels of coronary calcification. Age and VKA treatment were independently related to increased coronary calcium score.

Topics: Aged; Atrial Fibrillation; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multidetector Computed Tomography; Prospective Studies; Risk Factors; Stroke; Vascular Calcification; Vitamin K

RECORDAF is the first worldwide, prospective, observational survey of management of atrial fibrillation (AF) in unselected, community-based patients.. Primary outcomes were therapeutic success and clinical outcomes associated with rhythm-control and rate-control strategies.. Patients with recent-onset AF were included (n = 5,604). Treatment strategy (rhythm control or rate control) was noted at baseline. Follow-up was 12 months. Therapeutic success required that strategy was unchanged without clinical events. Further maintenance of sinus rhythm was required in the rhythm-control group, and heart rate ≤80 beats/min in the rate-control group.. Data from 5,171 patients were assessable. Therapeutic success was 54% overall (rhythm control 60% vs. rate control 47%), a result driven by control of AF: rhythm control, 81% vs. rate control, 74%. After adjustment for propensity score quintiles, the rhythm-control strategy was significantly related to superior therapeutic success (odds ratio: 1.34, 95% confidence interval: 1.15 to 1.55; p = 0.0002). Clinical events occurred in 18% of patients. The arrhythmia management strategy was not predictive of clinical events. The type (persistent), presence at baseline visit, and duration (>3 months) of AF, together with age older than 75 years and the presence of heart failure, predicted progression to permanent AF. The choice of rhythm control reduced the likelihood of AF progression (odds ratio: 0.20, 95% confidence interval: 0.17 to 0.25; p < 0.0001).. Clinical outcomes in AF patients were driven mainly by hospitalizations for arrhythmia/proarrhythmia and other cardiovascular causes, but not by the choice of rate or rhythm strategy. Rhythm-control patients progressed less rapidly to permanent AF.

Topics: Age Factors; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Glycosides; Catheter Ablation; Disease Progression; Electric Countershock; Electrocardiography; Female; Heart Failure; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Pacemaker, Artificial; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Registries; Stroke; Time Factors; Vitamin K

Topics: Atrial Fibrillation; Coronary Artery Disease; Female; Humans; Male; Stroke; Vascular Calcification; Vitamin K

Vitamin K antagonist (VKA) therapy is increasingly being used for the prevention of venous thromboembolism and stroke in atrial fibrillation. Bleeds are the major concern for VKA prescription, especially in very old patients who carry many risk factors for bleeding. We performed a large multicenter prospective observational study that enrolled very old patients to evaluate the quality of anticoagulation and the incidence of bleedings.. The study included 4093 patients ≥80 years of age who were naïve to VKA for thromboprophylaxis of atrial fibrillation or after venous thromboembolism. Patients' demographic and clinical data were collected, and the quality of anticoagulation and the incidence of bleeding were recorded. The follow-up was 9603 patient-years; median age at the beginning of follow-up was 84 years (range, 80 to 102 years). We recorded 179 major bleedings (rate, 1.87 per 100 patient-years), 26 fatal (rate, 0.27 per 100 patient-years). The rate of bleeding was higher in men compared with women (relative risk, 1.4; 95% confidence interval, 1.12 to 1.72; P=0.002) and among patients ≥85 years of age compared with younger patients (relative risk, 1.3; 95% confidence interval, 1.0 to 1.65; P=0.048). Time in therapeutic range was 62% (interquartile range, 49% to 75%). History of bleeding, active cancer, and history of falls were independently associated with bleeding risk in Cox regression analysis.. In this large study on very old patients on VKA carefully monitored by anticoagulation clinics, the rate of bleedings was low, suggesting that age in itself should not be considered a contraindication to treatment. Adequate management of VKA therapy in specifically trained center allows very old and frail patients to benefit from VKA thromboprophylaxis.

Topics: Age Distribution; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cooperative Behavior; Female; Hemorrhage; Humans; Incidence; Italy; Male; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Venous Thromboembolism; Vitamin K

Vitamin K antagonists (VKA) are the only registered oral anticoagulants for the treatment of venous thromboembolism (VTE). VKA have an unpredictable and highly variable effect on coagulation, with a high risk of under- and over-treatment. Novel anticoagulants, such as dabigatran and rivaroxaban, could be a very welcome replacement for VKA, as they show a predictable anticoagulant effect. Results of several phase II and III studies have shown the efficacy and safety of dabigatran and rivaroxaban in the prophylaxis and treatment of VTE, and for the prevention of stroke in atrial fibrillation. It remains to be shown whether these new anticoagulants have the same safety profile in daily clinical practice, where more vulnerable patients will be treated. Lack of information on the proper monitoring method or antidote in case of bleeding may also hinder the translation from science to clinical practice.

Topics: Acute Coronary Syndrome; Anticoagulants; Arthroplasty, Replacement, Hip; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Diet; Drug Interactions; Factor VIIa; Factor Xa Inhibitors; Humans; Kidney; Life Style; Monitoring, Physiologic; Morpholines; Recombinant Proteins; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Risk; Stroke; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Brain Ischemia; Humans; International Normalized Ratio; Prospective Studies; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Vitamin K

The superior efficacy of oral anticoagulation over aspirin for prevention of recurrent stroke in patients with atrial fibrillation is widely acknowledged. However, oral anticoagulation therapy is notorious for having a narrow therapeutic index, numerous drug and dietary interactions, and a significant risk of serious bleeding. The value of dual antiplatelet therapy for stroke prevention in patients with atrial fibrillation has been assessed in the ACTIVE A trial. In this study, the relative risk of primary events was significantly decreased in patients allocated clopidogrel and aspirin compared with patients receiving aspirin alone. However, the relative risk of major bleeding was also significantly increased. This article analyses critically the role of dual antiplatelet therapy for stroke prevention in patients with atrial fibrillation.

Topics: Atrial Fibrillation; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Vitamin K

Topics: Algorithms; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Cause of Death; Humans; Stroke; Vitamin K

Current guidelines for ischemic stroke prevention in atrial fibrillation or flutter (AFF) recommend Vitamin K antagonists (VKAs) for patients at high-intermediate risk and aspirin for those at intermediate-low risk. The cost-effectiveness of these treatments was demonstrated also in elderly patients. However, there are several reports that emphasize the underuse of pharmacological prophylaxis of cardio-embolism in patients with AFF in different health care settings.. To evaluate the adherence to current guidelines on cardio-embolic prophylaxis in elderly (> 65 years old) patients admitted with an established diagnosis of AFF to the Italian internal medicine wards participating in REPOSI registry, a project on polypathologies/polytherapies stemming from the collaboration between the Italian Society of Internal Medicine and the Mario Negri Institute of Pharmacological Research; to investigate whether or not hospitalization had an impact on guidelines adherence; to test the role of possible modifiers of VKAs prescription.. We retrospectively analyzed registry data collected from January to December 2008 and assessed the prevalence of patients with AFF at admission and the prevalence of risk factors for cardio-embolism. After stratifying the patients according to their CHADS(2) score the percentage of appropriateness of antithrombotic therapy prescription was evaluated both at admission and at discharge. Univariable and multivariable logistic regression models were employed to verify whether or not socio-demographic (age >80years, living alone) and clinical features (previous or recent bleeding, cranio-facial trauma, cancer, dementia) modified the frequency and modalities of antithrombotic drugs prescription at admission and discharge.. Among the 1332 REPOSI patients, 247 were admitted with AFF. At admission, CHADS(2) score was ≥ 2 in 68.4% of patients, at discharge in 75.9%. Among patients with AFF 26.5% at admission and 32.8% at discharge were not on any antithrombotic therapy, and 43.7% at admission and 40.9% at discharge were not taking an appropriate therapy according to the CHADS(2) score. The higher the level of cardio-embolic risk the higher was the percentage of antiplatelet- but not of VKAs-treated patients. At admission or at discharge, both at univariable and at multivariable logistic regression, only an age >80 years and a diagnosis of cancer, previous or active, had a statistically significant negative effect on VKAs prescription. Moreover, only a positive history of bleeding events (past or present) was independently associated to no VKA prescription at discharge in patients who were on VKA therapy at admission. If heparin was considered as an appropriate therapy for patients with indication for VKAs, the percentage of patients admitted or discharged on appropriate therapy became respectively 43.7% and 53.4%.. Among elderly patients admitted with a diagnosis of AFF to internal medicine wards, an appropriate antithrombotic prophylaxis was taken by less than 50%, with an underuse of VKAs prescription independently of the level of cardio-embolic risk. Hospitalization did not improve the adherence to guidelines.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Female; Fibrinolytic Agents; Guideline Adherence; Humans; Internal Medicine; Intracranial Embolism; Italy; Male; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Risk Factors; Stroke; Vitamin K

The RE-LY trial has shown that the oral direct thrombin inhibitor dabigatran etexilate is a valid replacement for oral anticoagulation with vitamin K antagonists (VKA) in patients with atrial fibrillation at thromboembolic risk. After a decade of failures, these results signify a breakthrough in anticoagulation management. This article summarizes the available evidence from the perspective of the practicing clinician: do the results apply to all patients with AF? And what considerations should we make when prescribing this new oral anticoagulant?. We review the trials searching for oral alternatives to VKA therapy, with emphasis on the RE-LY data.We have integrated available interaction data, and data on how to deal with side effects and (bleeding) complications with the direct thrombin inhibitor dabigatran etexilate.. abigatran etexilate is a viable alternative to VKA, improving efficacy and safety in many respects, for many patients, and likely preferred by most patients themselves. Choosing the dose should be based on patient-specific factors. These include the presence of coronary artery disease (with potential requirement of concomitant aspirin +/- clopidogrel), decreased renal function, age, low body weight, administration of otherAF drugs or P-glycoprotein inhibitors, a history of gastro-intestinal bleeding, and patient compliance.

Topics: Administration, Oral; Anticoagulants; Antithrombin Proteins; Atrial Fibrillation; Benzimidazoles; Dabigatran; Humans; International Normalized Ratio; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Vitamin K; Warfarin

Use of vitamin K antagonists (VKAs) for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) necessitates frequent monitoring of the international normalized ratio (INR) to avoid the increased risk of hemorrhage associated with excess anticoagulation, or ischemic stroke due to insufficient anticoagulation. We therefore developed a model to estimate the excess morbidity attributable to inadequate INR control in NVAF populations.. Equations expressing the risk of cerebrovascular events as a function of INR were generated using published data. Additional functions were developed to estimate the excess risk attributable to inferior INR control, using the clinical trial setting as the reference.. The derived risk functions were applied to French NVAF patients receiving anticoagulation in routine medical practice. This population achieved a time in therapeutic range (INR 2.0-3.0) of 59%, compared with 68% time in therapeutic range (TTR) in the SPORTIF III and V clinical trials. However, there was considerable variation in the TTR among patients in routine care, of whom 36% were in range for less than 50% of the time. Among this latter group, the relative risk, compared with the clinical trial setting, was 1.47 for ischemic stroke and 2.68 for intracranial hemorrhage. Conversely, for patients achieving a TTR greater than 50%, the relative risks for ischemic stroke and intracranial hemorrhage were 0.99 and 1.16, respectively.. This model permits estimation of the excess risk attributable to inferior INR control in NVAF populations receiving VKA anticoagulation, and has implications for public health planning and management.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Cerebral Hemorrhage; France; Humans; International Normalized Ratio; Models, Statistical; Morbidity; Public Health; Quality of Health Care; Risk Factors; Stroke; Vitamin K

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Stroke; Ticlopidine; Vitamin K

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Humans; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticlopidine; Treatment Outcome; Vitamin K; Warfarin

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

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Contraindications; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Stroke; Ticlopidine; Vitamin K; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Stroke; Ticlopidine; Vitamin K

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Incidence; Platelet Aggregation Inhibitors; Risk; Stroke; Ticlopidine; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Humans; International Normalized Ratio; Intracranial Embolism; Pyridines; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Hemorrhage; Humans; Phenprocoumon; Pyridines; Randomized Controlled Trials as Topic; Stroke; Vitamin K

In primary prevention, aspirin reduces the risk of stroke but not of myocardial infarction in women while in men only the risk of myocardial infarction but not stroke could be significantly reduced. Only aspirin has been shown to be safe and effective in large randomized trials in the first 48 hours after ischemic stroke. Aspirin/dipyridamole and clopidogrel both reduce the risk of a combined cardiovascular outcome in long-term secondary prevention compared to aspirin alone. More potent antiplatelet drugs or combination of aspirin and clopidogrel prevent more ischemic events, but also lead to more bleeding complications. No benefit of oral anticoagulants could be shown in patients with non-cardioembolic stroke. In patients with atrial fibrillation oral anticoagulation is more effective than aspirin in stroke prevention. The choice between oral anticoagulants and aspirin in these patients depends on age and the individual risk factor profile. Patients with symptomatic intracranial stenosis have a higher risk of intracerebral bleeding with oral anticoagulation compared to high dose aspirin. Aspirin is the recommended treatment in stroke patients with a patent foramen ovale.

Topics: Aged; Aspirin; Female; Humans; Ischemic Attack, Transient; Male; Platelet Aggregation Inhibitors; Primary Prevention; Recurrence; Safety; Stroke; Survival Analysis; Vitamin K

Patients with atrial fibrillation taking vitamin-K antagonists and undergoing invasive interventions or large surgery procedures are at highest risk of bleeding complications. Therefore, the temporary interruption of vitamin-K antagonists and bridging with heparin is a frequent clinical need, particularly in patients with high risk for stroke. The management of such patients is challenging because of the lack of randomized clinical trials assessing different periprocedural anticoagulation approaches and inconsistent recommendations from consensus groups. Recent non-randomized trials have helped to estimate the risks of thromboembolism and bleeding with "bridging" anticoagulation involving either low-molecular-weight heparin or intravenous unfractioned heparin. Nevertheless, there is still a clear need for randomized double-blinded controlled trials comparing efficacy and safety of the different "bridging" strategies, including unfractionated heparin and placebo comparators, in preventing thromboembolism for specific patients and procedures.

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

In this overview the actual guideline-recommendations for anticoagulation in atrial fibrillation and the problems of the currently available therapy are discussed. Furthermore an outlook over future developments in this field is given. Effective anticoagulation can prohibit thrombembolic events and is thus essential for the prognosis of patients suffering from atrial fibrillation. Until now vitamin-K-antagonists (VKAs) and acetylsalicylic acid (ASA) are available for oral anticoagulation in these patients. VKAs demonstrate a satisfying efficiency combined with rather high bleeding hazard. ASA on the other hand allows only moderate risk reduction with minimal side effects. Thus the guidelines recommend anticoagulation tailored to the individual risk, which can be evaluated by the CHADS2-Score. New therapeutic strategies, like the factor Xa inhibitor rivaroxaban or the factor II inhibitor dabigatran, are actually evaluated in phase III studies. These drugs bear the hope of higher efficiency combined with improved safety and much more comfortable use in the daily practice (e. g. no need for INR measurement, no dose adaptation).

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; Blood Coagulation; Blood Coagulation Factors; Dabigatran; Female; Humans; Middle Aged; Pyridines; Risk Factors; Stroke; Vitamin K

Transesophageal echocardiography (TEE) has been used to document the incidence of non-obstructive thrombosis (NOT) after mechanical prosthetic mitral valve replacement (MVR). The postoperative occurrence and unpredictable evolution of NOT complicate its management. The study aim was to examine the safety and efficacy of prolonged, combined administration of heparin and vitamin K antagonists (VKA) recommended for this indication.. All patients who underwent mechanical prosthetic MVR between July 1999 and December 2004 at the authors' institution were systematically studied with TEE immediately after surgery. Patients who presented with > or = 5 mm NOT were treated with combined heparin and VKA until TEE-confirmed resolution of the thrombus.. Among 256 patients who underwent 263 MVRs (seven reinterventions), 47 (17.9%) presenting with > or = 5 mm NOT received combined heparin and VKA for between 7 and 115 days (median 17 days). No thromboembolic or hemorrhagic events or deaths were observed during this period of observation. Four patients were treated with danaparoid and VKA because of thrombocytopenia induced by heparin before the diagnosis of NOT. Over a mean follow up of 39 months, one patient died from cancer and another from the sequelae of a stroke. In total, there were five NOT recurrences, three of which were complicated by embolic events without sequelae within eight months, and one by a recurrent stroke. In addition, three patients without demonstrable NOT recurrence suffered transient ischemic attacks.. Among this small sample of patients, combined heparin and VKA was well tolerated and effective, and could prevent reoperation or thrombolysis. These observations may warrant further study in a larger patient population.

Topics: Adult; Aged; Anticoagulants; Cause of Death; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Long-Term Care; Male; Middle Aged; Mitral Valve; Postoperative Complications; Stroke; Thrombosis; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cerebral Hemorrhage; Dose-Response Relationship, Drug; Humans; Intracranial Thrombosis; Phenotype; Risk Assessment; Stroke; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Oligosaccharides; Stroke; Thromboembolism; Vitamin K; Warfarin

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Incidence; Martinique; Nurse's Role; Nursing Assessment; Patient Compliance; Patient Education as Topic; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Quality of Health Care; Stroke; Treatment Outcome; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Risk Assessment; Stroke; Thromboembolism; Vitamin K

Topics: Administration, Oral; Antifibrinolytic Agents; Aspirin; Dipyridamole; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Stroke; Vitamin K

Anticoagulation therapy is recommended in patients with atrial fibrillation (AF) and risk factors for stroke. We studied the temporal trends in the prescription of vitamin K antagonists (VKA) in patients with a first hospital diagnosis of AF in Denmark, 1995-2002.. The Danish National Hospital Registry was used to identify subjects with a first hospital diagnosis of AF and the Danish Register of Medical Products Statistics to determine the proportion of these patients who claimed a prescription of VKA within 3 months from discharge.. Amongst 68 546 patients aged 50-99 years with a diagnosis of AF who survived 3 months following discharge, 24 991 (36%) patients claimed a prescription of VKA within 3 months. In both men and women a gradual increase in the use of VKA with time was observed, the relative increase being largest amongst the 80- to 99-year olds. In all age groups, the prescription of VKA was lower in women than in men, including patients with a prior or concurrent stroke.. From 1995 to 2002 the proportion of AF patients receiving VKA therapy increased significantly but the use of VKA therapy amongst women was lagging behind that of men. Even in patients with AF and prior stroke, the use of VKA seems to be less than optimal.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Denmark; Female; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Practice Patterns, Physicians'; Registries; Sex Factors; Stroke; Vitamin K

Patients with a supratherapeutic international normalised ratio (ST-INR) are at risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often by supplementing vitamin K or providing vitamin K-dependent factors; the exact therapeutic decision is based on the extent of the prolonged INR. Currently, ST-INRs are frequently observed in clinical practice due to the use of sensitive recombinant tissue thromboplastin reagents and automation. However, there are scant data correlating an ST-INR with various vitamin K-dependent factors. This prospective cohort study, set in a large tertiary care teaching hospital for the University of Texas Southwestern Medical Center at Dallas, defined the relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin therapy for more than 2 months. There was no significant relationship between the ST-INR and levels of important vitamin K-dependent factors II and X. These data support the recent guidelines that the management of an INR > 5.0 should be driven by the clinical determinants rather than specific INR values per se.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Blood Coagulation Factors; Factor X; Female; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Prospective Studies; Prothrombin; Regression Analysis; Stroke; Venous Thrombosis; Vitamin K; Warfarin

Atrial fibrillation, the most frequent arrhythmia, has a growing incidence with increasing age and the most important complication of the disease is thromboembolic events that may be prevented by antivitamin K. They are the most efficient therapeutic class for the prevention of these events but they are associated with an increased haemorrhagic risk leading to a reduced prescription in general practice. Optimisation of the management should be based on an individual evaluation of the thromboembolic and haemorrhagic risks, taking into account age, the presence of an associated heart disease, hypertension, diabetes, history of cerebrovascular event, history of previous haemorrhagic event and the ability to achieve a stable target INR. The challenge in ventricular arrhythmias lies in identifying a high risk of sudden death, mainly related to ventricular fibrillation. In patients with structural heart disease, left ventricular dysfunction is the strongest predictor of sudden death. Non invasive markers such as non sustained ventricular tachycardia, late ventricular potentials, decreased heart rate variability and baroreflex sensitivity, and repolarization altemans are further elements to assess risk. However, most of these markers have a poor positive predictive value and a low specificity. In patients with normal hearts, genetic predisposition may in the future identify high risk patients. The electrophysiologic study with programmed ventricular stimulation remains a costly and invasive method and only has a strong positive predictive value in ischemic cardiomyopathy. More precise algorithms for risk stratification are thus needed that may help the strategy of therapy with prophylactic implantable cardioverter defibrillator in the future.

Topics: 4-Hydroxycoumarins; Age Factors; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Baroreflex; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Diabetes Complications; Electrocardiography; Heart Diseases; Heart Rate; Hemorrhage; Humans; Hypertension; Indenes; International Normalized Ratio; Myocardial Ischemia; Risk Assessment; Risk Factors; Stroke; Tachycardia, Ventricular; Thromboembolism; Ventricular Dysfunction, Left; Ventricular Fibrillation; Vitamin K

Topics: Atrial Fibrillation; Blood Coagulation Tests; Capillaries; Diagnostic Errors; Female; Humans; International Normalized Ratio; Middle Aged; Stroke; Veins; Vitamin K

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

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Azetidines; Benzylamines; Drug Therapy, Combination; Humans; Prodrugs; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

The product of the growth arrest-specific gene 6 (GAS6), a ligand for the Axl, Sky, and Mer tyrosine kinase receptors, is a vitamin K-dependent protein, structurally related to anticoagulant protein S. Gas6-deficient mice are protected against thrombosis, demonstrating the importance of this protein in the cardiovascular system. The present study was aimed at determining the human GAS6 intron-exon structure and analyzing the gene for the presence of allelic variants that could be associated with atherothrombotic disease. Online analyses allowed us to localize 15 GAS6 exons and to determine the sequence of their intron-flanking regions, in a chromosome 13 region spanning 43.8 kb of DNA. SSCP analysis of PCR-amplified GAS6 exons with their intron-flanking regions from a minimum of 12 control DNA samples, revealed the presence of eight different variants, which were confirmed to be single nucleotide polymorphisms (SNPs). Three of them (c.1263G>C, c.1332C>T, and c.1869T>C) are localized in exons 11, 12, and 14, and appear to be neutral since they do not modify the encoded amino acid. The other SNPs (c.280+170C>G, c.712+26G>A, c.713-155C>T, c.834+7G>A, and c.1478-94C>G) are in introns 3, 7, 8, and 12. A preliminary analysis of five of these SNPs in a group of 110 healthy controls and 188 patients with atherothrombotic disease has revealed statistically significant differences between controls and stroke patients in the allelic distributions of one of these variants (c.834+7G>A in intron 8). The SNP identification in GAS6 reported here would be very useful in future association studies aimed at determining the physiologic role of GAS6 in stroke and other human diseases.

Topics: Alleles; Angina Pectoris; Animals; Base Sequence; Exons; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Humans; Intercellular Signaling Peptides and Proteins; Introns; Mice; Molecular Sequence Data; Myocardial Infarction; Polymorphism, Single Nucleotide; Rats; RNA Splice Sites; Stroke; Vitamin K

Peripheral vascular occlusive disease (PAOD) is frequently seen in patients suffering from coronary heart or cerebrovascular disease and is, considered as a prognostic predictor for the morbidity and mortality of this patient group. Thus, secondary antithrombotic and antiplatelet prophylaxis in these patients is not limited to achievement of long-term patency of the revascularized or recanalized arterial segment, but plays as well a pivotal role for the prevention of myocardial infarction and stroke. Generally, claudicants as well as patients undergoing percutaneous transluminal angioplasty (PTA), supragenicular femoro-popliteal artificial bypass surgery, aortofemoral, iliaco-femoral unilateral bypass, or aortobifemoral Y-graft implantation with unimpaired arterial outflow are treated life-long with low dose acetylsalicylic acid (ASA) 75-250 mg. On the other hand, those undergoing axillo-femoral, femoro-femoral crossover, aorto-profundal or femoro-popliteal infragenicular and femoro-distal venous bypass surgery should be treated with vitamin K antagonists. The role of Clopidogrel in secondary prevention after peripheral revascularization and recanalization still needs to be defined.

Topics: Administration, Oral; Angioplasty, Balloon; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Confidence Intervals; Dipyridamole; Drug Therapy, Combination; Embolectomy; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Iloprost; Intermittent Claudication; Leg; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thrombectomy; Ticlopidine; Time Factors; Vitamin K

Topics: Decision Making; Evidence-Based Medicine; Humans; Stroke; Treatment Outcome; Vitamin K