warfarin and Embolism

Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.. Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.. Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.. The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.

Topics: Administration, Oral; Amiodarone; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Cytochrome P-450 CYP3A Inhibitors; Embolism; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

Left ventricular thrombus (LVT) is a recognized complication of acute myocardial infarction which is associated with stroke. There has yet to be a published systematic review that focuses on outcomes for patients with LVT. We conducted a systematic review on treatments, adverse events and thrombus resolution in patients with LVT. Meta-analysis and numerical pooling were used to evaluate the difference in outcomes based on treatment and the presence or absence of LVT. A total of 39 studies were included (5475 patients with LVT and 356 589 patients with no LVT). The use of direct oral anticoagulants (DOACs) was associated with reduced mortality [RR, 0.66; 95% confidence interval (CI), 0.45-0.97; I2  = 9%] and bleeding (RR, 0.64; 95% CI, 0.48-0.85; I2  = 0%) compared to warfarin but there was a nonsignificant reduction in stroke/embolic events (RR, 0.95; 95% CI, 0.76-1.19; I2  = 3%). For patients with any treatment, the rate of stroke/embolic events, bleeding and mortality at follow-up of up to 12 months was 6.4, 3.7 and 7.9%, respectively. Pooled results from six studies that evaluated resolution at 6 months suggest that 80% of LVT were resolved. Apixaban was associated with the highest rate of (93.3%) whereas warfarin exhibited the lowest rate of resolution 73.1%. LVT is best managed with DOAC compared to warfarin therapy. An individualized approach to antithrombotic therapy is warranted as there appears to be no duration of therapy that clearly results in the resolution of all cases of LVT so follow-up imaging after discontinuation of anticoagulant is needed.

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

Findings of prior studies about the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients (≥80 years of age) with atrial fibrillation (AF) are controversial. So we performed a meta-analysis to evaluate the efficacy and safety of NOACs versus vitamin K antagonists (VKAs) in patients (≥80 years of age) with AF. A systematic review of PubMed, Cochrane, Embase, Web of Science and Chinese BioMedical databases was conducted until 1 October 2022. Studies reporting the effects and safety of NOACs versus warfarin in patients (≥80 years of age) with AF were included. Two authors independently performed study selection and data extraction. Discrepancies were resolved by consensus or through an independent third reviewer. Data were synthesised according to the Preferred Reporting Items for Systematic Reviews guidelines. We identified 15 studies providing data of 70 446 participants (≥80 years of age) suffering from AF. According to the meta-analysis (odds ratio (OR) (95% confidence interval, CI)), NOACs conferred better efficacy profile than VKAs in stroke and systemic embolism (0.8 (0.73-0.88)) and all-cause mortality (0.61 (0.57-0.65)). Otherwise, NOACs conferred a better safety profile than VKAs in major bleeding (0.76 (0.70-0.83)) and intracranial haemorrhage (ICH; 0.57 (0.47-0.68)). In conclusion, for patients (≥80 years of age) with AF, the risks of stroke and systemic embolism, all-cause mortality, were lower in NOACs compared to warfarin. The risks of major bleeding and ICH were also lower in NOACs compared to warfarin. NOACs showed better efficacy and safety than warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Stroke; Warfarin

Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke risk. This study aimed to evaluate the efficacy and safety of DOAC versus warfarin in patients with low stroke risk. An online literature search was conducted to retrieve studies comparing clinical outcomes between patients treated with DOAC versus warfarin for AF, reporting outcomes for patients at low or minimal risk of stroke (CHA

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Intracranial Hemorrhages; Risk Factors; Stroke; Treatment Outcome; Warfarin

Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US).. We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin.. Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs.. This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Retrospective Studies; Rivaroxaban; Stroke; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear.. We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3).. From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment.. DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Insurance Claim Review; Male; Patient Acuity; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; Taiwan; Warfarin

Topics: Anticoagulants; Antithrombins; Dabigatran; Embolism; Factor Xa Inhibitors; Heart Diseases; Heart Ventricles; Hemorrhage; Humans; Odds Ratio; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Warfarin

Anticoagulant treatment in non-valvular atrial fibrillation (AF) patients with severe chronic kidney disease (CKD) or on dialysis remains a matter of debate. The object of this study was to quantify the benefit-risk profiles of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis.. A comprehensive search of the Cochrane Library, PubMed, Ovid, and Google Scholar databases was performed for eligible studies that comparing the effect and safety of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were abstracted, and then pooled using a random-effects model.. A total of seven studies, one post hoc analysis of RCT and six observational cohorts, were included in this meta-analysis. Compared with warfarin use, the use of rivaroxaban or apixaban was significantly associated with reduced risks of all-cause death (HR = 0.82, 95% CI 0.72-0.93) and gastrointestinal bleeding (HR = 0.87, 95% CI 0.80-0.95). There were no significant differences in the risks of stroke or systemic embolism (rivaroxaban, HR = 0.71, 95% CI 0.43-1.19; apixaban, HR = 0.86, 95%CI 0.68-1.09) and major bleeding (rivaroxaban, HR = 0.96, 95% CI 0.64-1.45; apixaban, HR = 0.56, 95%CI 0.28-1.12).. Current evidence suggests that rivaroxaban or apixaban are safe and at least as effective as warfarin in patients with AF and stage 4-5 CKD or on dialysis.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Patient Acuity; Pyrazoles; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Warfarin

Data on the efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer are limited. Therefore, we conducted a meta-analysis to compare the efficacy and safety between NOACs and warfarin in this population.. A comprehensive search of the PubMed, Embase, and Cochrane databases for articles published through July 2020 was performed. An evaluation of each study was conducted, and data were extracted. Pooled odds ratio (OR) estimates and 95% CIs were calculated.. Eight studies (3 randomized controlled trials (RCTs) and 5 retrospective cohort studies) involving a total of 24,665 patients were included. Among the RCTs, there were no significant differences in the rates of stroke or systemic embolism (OR=0.69; 95% CI, 0.45-1.06; P=0.09), venous thromboembolism (OR=0.91; 95% CI, 0.33-2.52; P=0.86), myocardial infarction (OR=0.74; 95% CI, 0.44-1.23; P=0.24), major bleeding (OR=0.81; 95% CI, 0.61-1.06; P=0.12), or major or nonmajor clinically relevant bleeding (OR= 0.98; 95% CI, 0.82-1.19; P=0.86) between the NOAC and warfarin groups. Among the observational studies, patients who used NOACs had a significantly lower risk than those who used warfarin. The prevalence rates of ischemic stroke (OR=0.51; 95% CI, 0.28-0.92; P=0.02), VTE (OR=0.50; 95% CI, 0.41-0.60; P<0.00001), major bleeding (OR=0.28; 95% CI, 0.14-0.55; P=0.0002), and intracranial or gastrointestinal bleeding (OR=0.59; 95% CI, 0.37-0.92; P=0.02) were significantly reduced in the NOAC group.. Our meta-analysis confirms that NOACs are as safe and effective as warfarin and can be applied in the real world; this data can serve as a reference for clinical doctors for formulating treatment strategies.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Observational Studies as Topic; Randomized Controlled Trials as Topic; Stroke; Warfarin

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

We performed this meta-analysis to compare the efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF). The PubMed and Embase databases were systematically searched until July 2019 for eligible studies that comparing the effect between any reduced-dose NOAC and warfarin in patients with AF. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled by using a random-effects model. A total of 14 observational cohorts were included. Compared with warfarin use, the use of reduced-dose NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.83; 95% CI 0.74-0.93), ischemic stroke (RR, 0.87; 95% CI 0.77-0.98), major bleeding (RR, 0.71; 95% CI 0.60-0.84), intracranial hemorrhage (RR, 0.51; 95% CI 0.44-0.60), and gastrointestinal bleeding (RR, 0.72; 95% CI 0.54-0.94), but not all cause death (RR, 0.84; 95% CI 0.67-1.06). In the subgroup analyses, all NOAC users had lower or similar rates of thromboembolic and bleeding events; and the reductions in stroke or systemic embolism, all-cause death, major bleeding, and gastrointestinal bleeding were more prominent in Asians than non-Asians. In conclusion, current published data suggest that the use of reduced-dose NOACs is non-inferior to warfarin in patients with AF (in particular Asians).

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Humans; Warfarin

Data of non-vitamin K antagonist oral anticoagulants (NOACs) in current management of atrial fibrillation (AF) are predominantly derived from North American and European regions. However, the effects of NOACs for stroke prevention in Latin America remain unclear. Therefore, we aimed to compare the efficacy and safety of NOACs with warfarin in Latin American patients with AF.. The PubMed and Embase databases were systematically searched until July 12, 2019 for applicable randomized clinical trials. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model.. Four trials involving 8943 Latin American patients were included in this meta-analysis. In anticoagulated patients with AF, Latin American patients had higher rates of stroke or systemic embolism and all-cause death compared with non-Latin American subjects. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism, major bleeding, intracranial bleeding, and any bleeding in Latin American patients. There were no significant differences in the risks of ischemic stroke, all-cause death, and gastrointestinal bleeding between Latin and non-Latin American groups. All the interactions between Latin and non-Latin American groups about efficacy and safety outcomes of NOACs compared with warfarin were non-significant (all Pinteraction > .05).. Our meta-analysis suggested that the use of NOACs was at least non-inferior to warfarin use for stroke prevention in Latin American patients with AF.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Hispanic or Latino; Humans; Latin America; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

Given the huge burden of atrial fibrillation (AF) and AF-related stroke in Asia, stroke prevention represents an urgent issue in this region. We herein performed a network meta-analysis to examine the role of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with AF.. A systematic search of the publications was conducted in PubMed and Embase databases for eligible studies until July 2019. The odds ratios (ORs) and 95% confidence intervals (CIs) were regarded as the effect estimates. The surface under the cumulative ranking area (SUCRA) for the ranking probabilities was calculated.. A total of 17 studies were included. For comparisons of NOACs vs warfarin, dabigatran (OR = 0.77, 95% CI 0.68-0.86), rivaroxaban (OR = 0.72, 95% CI 0.65-0.81), apixaban (OR = 0.56, 95% CI 0.49-0.65), but not edoxaban reduced the risk of stroke or systemic embolism, wheres dabigatran (OR = 0.56, 95% CI 0.41-0.76), rivaroxaban (OR = 0.66, 95% CI 0.50-0.86), apixaban (OR = 0.49, 95% CI 0.36-0.66), and edoxaban (OR = 0.34, 95% CI 0.24-0.49) decreased the risk of major bleeding. In reducing the risk of stroke or systemic embolism, apixaban and rivaroxaban ranked the best and second best (SUCRA 0.2% and 31.4%, respectively), followed by dabigatran (50.2%), edoxaban (75.2%), and warfarin (93.0%). In reducing the risk of major bleeding, edoxaban, and apixaban ranked the best and second best (1.5% and 30.8%, respectively), followed by dabigatran (48.4%), rivaroxaban (69.2%), and warfarin (100%).. NOACs were at least as effective as warfarin, but more safer in Asians with AF. Apixaban was superior to other NOACs for reducing stroke or systemic embolism, while edoxaban showed a better safety profile than other NOACs.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Asia; Asian People; Atrial Fibrillation; Cost of Illness; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Network Meta-Analysis; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Safety; Stroke; Thiazoles; Warfarin

There is a lack of clear benefit and a potential risk of bleeding with direct oral anticoagulant (DOAC) use in chronic kidney disease (CKD) and dialysis patients with atrial fibrillation. The objective of this study was to evaluate how treatment with DOACs affects stroke and bleeding outcomes compared with warfarin or aspirin.. We conducted a systematic review of randomized controlled trials, cohort studies and case series, and searched electronic databases from 1946 to 2017. Studies evaluating stroke and bleeding outcomes with DOAC use in CKD and dialysis patients were included.. From 8008 studies, 10 met the inclusion criteria. For moderate CKD patients (estimated glomerular filtration rate  <60 mL/min/1.73 m2), there was no difference in stroke outcomes between dabigatran 110 mg [hazard ratio (HR) 0.78, 95% confidence interval (95% CI) 0.51-1.21], rivaroxaban (HR 0.82-0.84, 95% CI 0.25-2.69) and edoxaban (HR 0.87, 95% CI 0.65-1.18) versus warfarin. Dabigatran (150 mg twice daily) and apixaban reduced risk of stroke or systemic embolism significantly more than warfarin for moderate CKD patients (HR 0.55, 95% CI 0.34-0.89 and HR 0.61, 95% CI 0.39-0.94, respectively). Edoxaban and apixaban were associated with reduced major bleeding events (HR 0.50-0.76) compared with warfarin. Rivaroxaban and dabigatran 110 mg and 150 mg showed no significant difference in major bleeding versus warfarin. In hemodialysis (HD) patients, there was no difference in stroke outcomes between apixaban, dabigatran [relative risk (RR) 1.71, 95% CI 0.97-2.99] or rivaroxaban (RR 1.8, 95% CI 0.89-3.64) versus warfarin. In HD patients, rivaroxaban and dabigatran were associated with an increased major bleeding risk (RR 1.45-1.76), whereas there was no major bleeding difference with apixaban compared to warfarin.. The heterogeneity of major bleeding and stroke definitions of the 10 included studies.. Clinicians should continue to weigh the risk of stroke versus bleeding before prescribing DOACs in the CKD and dialysis population.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Dabigatran; Embolism; Glomerular Filtration Rate; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical factors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dose NOACs when given as pre-specified in pivotal trials.. Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69-1.03)] and on major bleeding [RR 0.70 (95% CI 0.50-0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77-0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70-1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each).. Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.

Topics: Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiazoles; Warfarin

Data regarding the efficacy and safety of warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce.. Fifteen studies (7 comparing NOAC vs warfarin and 8 comparing warfarin vs no anticoagulant) were identified comprising 78,053 patients. Warfarin (vs no anticoagulant) was associated with reduced risk of ischemic stroke (risk ratio [RR] = 0.68; 95% confidence interval [CI] 0.55-0.84]) and mortality (RR = 0.70; 95% CI 0.62-0.78). In comparison to warfarin, NOAC use lowered the risk of ICH (RR = 0.43; 95% CI 0.33-0.56), stroke. Among patients with CKD treated with oral anticoagulants, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Intracranial Hemorrhages; Mortality; Renal Insufficiency, Chronic; Stroke; Warfarin

Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Interventional left atrial appendage occlusion (LAAO) has emerged as a valid alternative to oral anticoagulation (OAC) therapy for the prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). Areas covered: Antithrombotic therapy following interventional LAAO is critical in balancing the risk of thromboembolism and bleeding during the endothelialization of the implanted devices. In this article, the most recent clinical trials are reviewed and the current real-world antithrombotic strategies following LAAO device implantation are discussed. Expert commentary: For patients eligible for OAC and receiving a Watchman device, the most solid scientific evidence exists for warfarin plus aspirin for 45 days followed by dual antiplatelet therapy (DAPT) for 6 months and a lifelong aspirin therapy. In real-world most patients are being treated with DAPT for 3-6 months. Alternatively, the Watchman was approved for 3 months of novel OAC (NOAC) therapy in conjunction with aspirin. For all other devices, DAPT for 1-6 months has been used in the vast majority of cases. Considering major bleeding as the predominant complication following LAAO, evidence suggests that short-term DAPT (6 weeks) or single antiplatelet therapy using aspirin may be a viable option.

Topics: Anticoagulants; Antifibrinolytic Agents; Aspirin; Atrial Appendage; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Dabigatran is a kind of oral anticoagulant and there was little review only about dabigatran and warfarin used in patients with atrial fibrillation. This meta-analysis only assesses the dabigatran and warfarin used in patients with atrial fibrillation.. Cochrane Library, PubMed, Clinical Trials.gov, CNKI, and WanFang databases were searched. The primary endpoint was the incidence of stroke and the second endpoints were the incidence of bleeding and embolic events.. Six RCTs and 20086 patients were included in our meta-analysis. No significant difference was obtained between 110 mg dabigatran and warfarin on the endpoint of stroke (risk ratio (RR), 0.90; 95% confidence interval [CI], 0.71-1.12; P = .34; I = 0%) and embolic events p (RR, 0.89; 95% CI, 0.71-1.12; P = .32; I = 0%). However, the 110 mg dabigatran associated lower incidence of bleeding (RR, 0.81; 95% CI, 0.69-0.95; P = .01; I = 0%) compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower rate of stroke (RR, 0.96; 95% CI, 0.83-1.12; P = .62; I = 0%) and embolic events (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%) but similar in the incidence of bleeding (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%).. No significant difference was obtained between 110 mg dabigatran and warfarin in the incidence of stroke and embolic events. However, the 110 mg dabigatran associated lower incidence of bleeding compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower incidence of stroke and embolic events but similar in the incidence of bleeding.

Topics: Adult; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

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

To determine the role of warfarin (WF) prophylaxis in the prevention of left ventricular thrombus (LVT) formation and subsequent embolic complications following an anterior ST elevation myocardial infarction (STEMI) complicated by reduced left ventricular ejection fraction (LVEF) and wall motion abnormalities.. The role of oral anticoagulation prophylaxis, in addition to dual antiplatelet therapy (DAPT), in the current era of percutaneous coronary intervention has not been well studied, despite being a class IIb recommendation in the AHA/ACC STEMI guidelines.. The Cochrane search strategy was used to search PubMed, Embase and the Cochrane library for relevant results. Four studies, two retrospective, one prospective registry, and a randomized feasibility control trial met criteria for inclusion. Data was pooled using a random effects model and reported as odds ratios (OR) with their 95% confidence intervals (CI). Primary outcomes of interest were rate of stroke, major bleeding and mortality.. Pooled analysis included 526 patients in the No WF group and 347 patients in the WF group. No statistical difference in rate of stroke (OR: 2.72 [95% CI: 0.47-15.88; p=0.21]) or mortality (OR: 1.50 [95% CI 0.29-7.71; p=0.63]) was observed. Major bleeding was significantly higher in the WF group (OR: 2.56 [95% CI: 1.34-4.89; p=0.004]).. The routine use of DAPT and WF for prophylaxis against LVT formation following an anterior STEMI with associated decrease in LVEF and wall motion abnormalities, appears to result in no mortality benefit or reduction in stroke rates, but may increase the frequency of major bleeding.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anterior Wall Myocardial Infarction; Anticoagulants; Chi-Square Distribution; Embolism; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Contraction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Stroke Volume; Thrombosis; Treatment Outcome; Ventricular Function, Left; Warfarin; Young Adult

Renal impairment increases risk of stroke and systemic embolic events and bleeding in patients with atrial fibrillation. Direct oral anticoagulants (DOACs) have varied dependence on renal elimination, magnifying the importance of appropriate patient selection, dosing, and periodic kidney function monitoring. In randomized controlled trials of nonvalvular atrial fibrillation, DOACs were at least as effective and associated with less bleeding compared with warfarin. Each direct oral anticoagulant was associated with reduced risk of stroke and systemic embolic events and major bleeding compared with warfarin in nonvalvular atrial fibrillation patients with mild or moderate renal impairment. Renal function decrease appears less impacted by DOACs, which are associated with a better risk-benefit profile than warfarin in patients with decreasing renal function over time. Limited data address the risk-benefit profile of DOACs in patients with severe impairment or on dialysis.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Pharmaceutical Research; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Risk Assessment; Rivaroxaban; Stroke; Therapeutic Equivalency; Thiazoles; Warfarin

Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin.. To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD.. We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.. We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4).. Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE.. Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin.. Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Thiazoles; Warfarin

Enzalutamide, a novel, oral androgen receptor antagonist used for the treatment of metastatic, castration-resistant prostate cancer, has been shown to improve overall and progression-free survival, prolong time to initiation of chemotherapy, reduce skeletal-related events, and carry a favorable adverse effect profile. Metastatic prostate cancer is a disease of older men, a population with an increased incidence of medical comorbidities warranting anticoagulation. Prostate cancer itself, along with some of its therapies, is also prothrombotic. Enzalutamide interacts with several anticoagulants through various mechanisms, making their concurrent use clinically challenging. As such, complex decisions about anticoagulation in these patients are frequently encountered by treating physicians. In this review, we describe the potential interactions between enzalutamide and various anticoagulants, and suggest management paradigms based on the current body of knowledge for patients with atrial fibrillation, venous thromboembolism, and mechanical heart valves.

Topics: Androgen Receptor Antagonists; Anticoagulants; Atrial Fibrillation; Benzamides; Dabigatran; Drug Interactions; Embolism; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Male; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Despite the information provided by clinical trials is important, there are relevant clinical differences between those patients included in clinical trials and data of daily outpatient clinics. As a result, in some cases, the results of randomized clinical trials could not be directly applied to clinical practice. In this context, to perform «real-life» registries is mandatory. In the ROCKET-AF study, rivaroxaban, a once-daily direct oral anticoagulant, was at least as effective as warfarin for preventing stroke or systemic embolism, with similar rates of major bleeding, but with a lesser risk of intracranial, critical and fatal bleedings. In the last years, different large registries have confirmed that rivaroxaban is effective and even safer in real-life patients than in ROCKET-AF. The aim of this review is to update the current evidence about the efficacy, effectiveness and safety of rivaroxaban in real-life patients.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Rivaroxaban; Stroke; Warfarin

Patients with atrial fibrillation have an increased risk for stroke, systemic embolism and cardiovascular events, including myocardial infarction and cardiovascular death. However, the majority of studies that have analyzed the efficacy of anticoagulants have been focused only on their effects on the risk of stroke. Areas covered: The available evidence about the association between atrial fibrillation and cardiovascular disease as well as the effects of oral anticoagulation on cardiovascular death and myocardial infarction, with a particular focus on direct oral anticoagulants, was updated in this review. Expert opinion: The management of patients with atrial fibrillation should not be limited to the prevention of stroke, but should also include the prevention of cardiovascular events. Despite treatment with vitamin K antagonists, many patients with atrial fibrillation still develop cardiovascular complications, particularly individuals whose anticoagulation is difficult to control. Direct oral anticoagulants overcome the majority of limitations of vitamin K antagonists and compared with warfarin, they lead to a greater reduction in the risk of stroke or systemic embolism, all-cause mortality, and intracranial hemorrhage. Although these drugs can only be compared indirectly, it seems that not all direct oral anticoagulants are equal with regard to the prevention of myocardial infarction.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Embolism; Humans; Myocardial Infarction; Stroke; Warfarin

The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin for stroke prevention in many patients with nonvalvular atrial fibrillation. Edoxaban, an oral factor Xa inhibitor, is the newest entrant in this class. Results of the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation (ENGAGE AF) study demonstrate that edoxaban is noninferior to warfarin for prevention of stroke and systemic embolic events, and is associated with significantly less major bleeding, including intracranial bleeding, and reduced cardiovascular mortality. With a net clinical benefit over warfarin, edoxaban is well positioned as a choice among the NOACs, which include dabigatran, rivaroxaban, and apixaban. But how will clinicians choose amongst them? The purpose of this paper is to (a) place the ENGAGE AF trial results into context with results of the studies with the other NOACs, and (b) aid clinicians in selection of the right anticoagulant for the right atrial fibrillation patient.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Research Design; Rivaroxaban; Stroke; Thiazoles; Warfarin

Atrial fibrillation (AF) and chronic kidney disease (CKD) are disorders with increasing prevalence. The presence of CKD increases the risk of incident AF and vice versa, and the presence of AF may accelerate CKD progression. Nearly a third of patients with established CKD also have AF, whilst half of AF patients may have some degree of renal dysfunction. Both AF and CKD are associated with increased cardiovascular morbidity and mortality, including significantly increased risk of stroke or systemic embolism. Oral anticoagulant therapy (OAC), either with vitamin K antagonists or with non-vitamin K oral anticoagulants (NOACs) is essential to optimise prevention of stroke and systemic embolism in AF patients with one or more stroke risk factors, and NOACs are more convenient and generally safer than vitamin K antagonists mostly due to consistently reduced risk of intracranial bleeding. The use of OAC must be balanced against the risk of OAC-related bleeding, which depends on the presence of bleeding risk factors. Renal failure is a well-established bleeding risk factor and renal function should be routinely assessed in all patients presenting with AF. Since the risk of bleeding increases in parallel with CKD severity, the clinical decision to use OAC in AF patients with severe CKD may be challenging. In this review article we summarize the OAC agents currently used in clinical practice and discuss the role of NOACs for stroke prevention in patients with AF and CKD.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Embolism; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

Direct oral anticoagulants are being presented as alternatives to warfarin for preventing stroke in patients with atrial fibrillation. Yet direct comparative trials between these agents in prevention of acute limb ischemia (ALI) are unavailable so far.. To conduct an adjusted indirect comparison meta-analysis between direct oral agents for prevention of acute limb ischemia in atrial fibrillation.. We conducted a systematic literature review searching electronic databases (MEDLINE and Embase) and the Cochrane Library from January 1990 through November 2014. Two blinded investigators reviewed all potentially relevant articles in a parallel manner by using a priori defined criteria. To assess the long-term efficacy and safety of these agents, only randomized clinical trials (RCTs) with follow-up durations of >1 year were included. The primary efficacy outcome was the end point of acute limb ischemia and/or extremity embolism.. A total of 44,563 patients from three RCTs met criteria for inclusion. Patients randomized to direct oral anticoagulants had a non-significant decreased risk for acute limb ischemia (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.26-1.2). In the analysis between agents, however, rivaroxaban significantly lowered the risk of ALI compared to warfarin (RR: 0.23, 95% CI: 0.064-0.82), apixaban (RR: 0.26, 95% CI: 0.081-0.83), and dabigatran (RR: 0.24, 95% CI: 0.077-0.83).. Significant differences in prevention of acute limb ischemia may exist between oral anticoagulant agents in patients with atrial fibrillation. Rivaroxaban lowers the risk of limb embolism versus warfarin, apixaban and dabigatran.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Humans; Ischemia; Leg; Odds Ratio; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

The management of stroke prevention among patients with atrial fibrillation (AF) has changed in the last few years. Despite the benefits of new oral anticoagulants (NOACs), decisions about the optimal agent remain a challenge. We provide a visual aid tool to guide clinicians and patients in the decision process of selecting oral anticoagulants for stroke prevention.. We created visual plots representing benefits of warfarin versus NOACs from a meta-analysis comprising 58,541 participants. Visual plots (Cates plots) were created using software available at nntonline.net. The primary outcome was stroke or systemic embolism during the study period.. In the chosen meta-analysis, 29,312 participants received a NOAC and 29,229 participants received warfarin. For every 1000 patients with AF, 38 would have a stroke or systemic embolic event in the warfarin group compared to 31 in the NOAC group (RR .81; 95% CI .73-.91). Fifteen patients would develop an intracranial hemorrhage in the warfarin group compared to 7 in the NOAC group (RR .48; 95% CI .39-.59). Conversely, 25 patients would develop gastrointestinal bleeding in the NOAC group compared to 20 in the warfarin group (RR 1.25; 95% CI 1.01-1.55).. For every 1000 treated individuals with AF, NOACs would prevent stroke or systemic embolism in 7 additional patients and cerebral hemorrhage in 8 additional patients compared to warfarin. On the other hand, 5 more patients would develop gastrointestinal bleeding with NOACs compared to warfarin. These data are visually shown in Cates plots, facilitating conversations with patients regarding anticoagulation decisions.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Audiovisual Aids; Decision Support Techniques; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Odds Ratio; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Software; Stroke; Treatment Outcome; Warfarin

Cryptogenic stroke is one-fourth among cerebral infarction, but most of them could be ascribed to embolic stroke. ESUS was proposed for unifying embolic stroke of undetermined sources by Hart et al. in 2014. The etiologies underlying ESUS included minor-risk potential cardioembolic sources, covert paroxysmal atrial fibrillation, cancer-associated coagulopathy and embolism, arteriogenic emboli, and paroxysmal embolism. Extensive evaluation including transesophageal echocardiography and cardiac monitoring for long time could identify the etiology of these patients. Although anti-platelet drug is recommended in ESUS in the current guideline, clinical trials are ongoing to determine the efficacy of non-vitamin K antagonist oral anticoagulant in ESUS patients.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Blood Coagulation Disorders; Clinical Trials as Topic; Embolism; Foramen Ovale, Patent; Humans; Intracranial Embolism; Neoplastic Cells, Circulating; Platelet Aggregation Inhibitors; Stroke; Thrombolytic Therapy; Warfarin

This study investigated the efficacy and safety of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF) by a meta-analysis.. AF is quite prevalent in patients with HF.. Four phase III clinical trials comparing NOACs to warfarin in patients with AF were included. Each patient was defined as affected by HF according to the criteria of the trial in which the patient was enrolled. Pre-specified outcomes were the composite of stroke/systemic embolism (SSE); major, intracranial, and any bleeding; and cardiovascular (CV) and all-cause death.. A total of 55,011 patients were enrolled, 26,384 (48%) with HF, and 28,627 (52%) without HF; 27,518 receiving NOACs and 27,493 receiving warfarin (median, 70 years of age; 36% females; follow-up: 1.5 to 2.8 years). Rates of SSE (relative risk [RR]: 0.98; 95% confidence interval [CI]: 0.90 to 1.07]; p = 0.68) and major bleeding (RR: 0.95; 95% CI: 0.88 to 1.03; p = 0.21) were comparable in patients with and without HF. HF patients had reduced rates of any (RR: 0.86; 95% CI: 0.81 to 0.91; p < 0.01) and intracranial (RR: 0.74 95% CI: 0.63 to 0.88; p < 0.01) bleeding but increased rates of all-cause (RR: 1.70 95% CI: 1.31 to 2.19; p < 0.01) and CV death (RR: 2.05 95% CI: 1.66 to 2.55; p < 0.01). NOACs, compared with warfarin significantly reduced SSE and major, intracranial, and any bleeding, regardless of the presence or absence of HF (p. Patients with AF and HF had increased mortality but reduced rates of intracranial and any bleeding compared with the no-HF patients, with no differences in rates of SSE and major bleeding. NOACs significantly reduced SSE, major bleeding, and intracranial hemorrhage in HF patients. No interactions in efficacy and safety of NOACs were observed between AF patients with and without HF.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Dabigatran; Embolism; Factor Xa Inhibitors; Heart Failure; Hemorrhage; Humans; Intracranial Hemorrhages; Mortality; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Warfarin

The WATCHMAN left atrial appendage closure (LAAC) technology is a percutaneously delivered permanent cardiac implant placed in the LAA. This device is designed to reduce the risk of stroke and systemic embolism in warfarin-eligible patients with nonvalvular atrial fibrillation. The first circulatory system device panel reviewed the Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) study in 2009, and a "not approvable" letter was issued by the US Food and Drug Administration (FDA) based on safety concerns. Subsequently, the FDA, collaboratively with the sponsor, designed a new Prospective Randomized Evaluation of the WATCHMAN LAAC Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy (PREVAIL) trial to address the earlier study limitations. A second panel was convened in December 2013 to review the results of PREVAIL and additional long-term follow-up data from PROTECT AF. The second panel voted favorably 13 to 1 that the benefits of the WATCHMAN LAAC therapy do outweigh the risks for use in patients who meet the criteria specified in the proposed indication. Subsequently, and during the premarket approval review, updated data from the PREVIAL study revealed more ischemic strokes in the WATCHMAN group, corresponding to a total of 13 ischemic strokes in the WATCHMAN group versus 1 in the control group. As a result of these strokes, the FDA called for a third panel to assess the benefit-risk profile of the WATCHMAN device. This summary aims to describe the discussions and recommendations made during the panel meetings.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Device Approval; Embolism; Humans; Prostheses and Implants; Risk Assessment; Septal Occluder Device; Stroke; United States; United States Food and Drug Administration; Warfarin

Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter.

Topics: Anticoagulants; Antithrombins; Embolism; Emergency Service, Hospital; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Thrombosis; 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

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

Despite its lack of efficacy, aspirin is commonly used for stroke prevention in atrial fibrillation. Since prior studies have suggested a benefit of low-intensity anticoagulation over aspirin in the prevention of vascular events, the aim of this systematic review was to compare the outcomes of patients with non-valvular atrial fibrillation treated with low-intensity anticoagulation with Vitamin K antagonists or aspirin.. We conducted a systematic review searching Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, from 1946 to October 14th, 2015. Randomized controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a low-intensity anticoagulation compared to patients treated with aspirin. The primary outcome was a combination of ischemic stroke or systemic embolism. The random-effects model odds ratio was used as the outcome measure.. Our initial search identified 6309relevant articles of which three satisfied our inclusion criteria and were included. Compared to low-intensity anticoagulation, aspirin alone did not reduce the incidence of ischemic stroke or systemic embolism OR 0.94 (95% CI 0.57-1.56), major bleeding OR 1.06 (95% CI 0.42-2.62) or vascular death OR 1.04 (95% CI 0.61-1.75). The use of aspirin was associated with a significant increase in all-cause mortality OR 1.66 (95% CI 1.12-2.48).. In patients with non-valvular atrial fibrillation, aspirin provides no benefits over low-intensity anticoagulation. Furthermore, the use of aspirin appears to be associated with an increased risk in all-cause mortality. Our study provides more evidence against the use aspirin in patients with non-valvular atrial fibrillation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Atrial Fibrillation; Embolism; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Stroke; Warfarin

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes.. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity.. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045).. This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.. None.

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

Published data on the association between vitamin K epoxide reductase complex 1 (VKORC1)-1639G > A polymorphism and warfarin dose requirement are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed.. Studies were identified in English-language articles by search of PubMed and Embase database (inception to July 2013). A total of 32 prospective clinical trials involving 5005 patients were identified and included for analysis. Overall, the weighted mean maintenance dosage of warfarin in patients with the -1639AA genotype decreased 2.62 mg/d compared with that in the -1639GG genotype patients (95% CI -3.10 to -2.14; P < 0.00001) when 24 eligible studies were pooled into the meta-analysis. Furthermore, significantly lower warfarin dose requirement was found in patients with GA genotype versus GG genotype (WMD, -1.32; 95% CI -1.67 to -0.96; P < 0.00001). In the subgroup analysis by ethnicity, statistically significant lower maintenance dosage of warfarin in patients with the AA genotype versus GG genotype were found in both Caucasians (WMD, -2.47; 95% CI -2.92 to -2.03; P < 0.00001) and Asians (WMD, -2.84; 95% CI -4.57 to -1.11; P = 0.001).. This meta-analysis indicated that the VKORC1-1639G > A genetic polymorphism is associated with the variation of interindividual warfarin dose requirement in different ethnic populations.

Topics: Anticoagulants; Asian People; Atrial Fibrillation; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Embolism; Genetic Markers; Genotype; Humans; Polymorphism, Single Nucleotide; Stroke; Thrombosis; Vitamin K Epoxide Reductases; Warfarin; White People

In patients with non-valvular atrial fibrillation (AF), direct-acting oral anticoagulants (DOACs) are at least non-inferior to warfarin for the prevention of stroke and systemic embolism. The main objective of this study was to obtain reliable and precise estimates for all-cause mortality, vascular mortality and bleeding mortality in patients with AF receiving a DOAC or warfarin for stroke prevention.. A meta-analysis was performed on phase 3 randomized trials that compared a DOAC with warfarin for stroke prevention in AF. Published data were pooled by use of the DerSimonian random-effect model, with revman 5.2 and comprehensive meta analysis software version 2. The results were presented as risk ratios (RRs), absolute risk reduction (ARR), and number-needed-to-treat (NNT).. A total of 71 683 patients were included in this meta-analysis from four randomized controlled trials (median patient follow-up: 1.8-2.8 years) that compared a DOAC with warfarin for stroke prevention in AF. As compared with warfarin, DOACs significantly reduced all-cause mortality (RR 0.89, 95% confidence interval [CI] 0.85-0.94; ARR 0.76%, 95% CI 0.39-1.13%; NNT = 132), vascular mortality (RR 0.88, 95% CI 0.82-0.94; ARR 0.53%, 95% CI 0.23-0.83%; NNT = 189), and bleeding mortality (RR 0.54, 95% CI 0.44-0.67; ARR 0.32%, 95% CI 0.21-0.43%; NNT = 313).. As compared with warfarin therapy for stroke prevention in patients with AF, DOACs significantly reduce all-cause mortality, vascular mortality, and bleeding mortality. This mortality benefit appears to be driven by the reduction in vascular-related and bleeding-related mortality, which, in turn, may be related to the reduction in intracranial bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Randomized Controlled Trials as Topic; Risk; Stroke; Treatment Outcome; Warfarin

Patients with non-valvular atrial fibrillation (NVAF) are at risk for stroke and systemic embolism (SSE), and this risk can be decreased with adjusted-dose warfarin. Warfarin, however, is cumbersome to use and requires at least monthly laboratory monitoring. Three new oral anticoagulants (NOACs) that are less cumbersome have been approved as alternatives to warfarin for SSE prevention in NVAF. Selecting a patient-specific alternative to warfarin can be confusing for pharmacists and clinicians. This review details clinical parameters to consider when choosing an alternative to warfarin for a specific patient and summarizes them in a Comparison Table.. Using available clinical evidence from pivotal trials, US FDA- and Health Canada-approved prescribing information and post-marketing observations, this review provides a summary of important clinical variables for clinicians to consider when choosing patient-centred anticoagulant alternatives to warfarin for prevention of SSE in NVAF.. Dabigatran, rivaroxaban and apixaban are approved alternatives to warfarin for primary and secondary prevention of SSE in patients with NVAF. Additionally, apixaban has also been compared to aspirin in patients with NVAF that were considered unsuitable for vitamin K antagonist therapy. Prospective consideration of age, weight, hepatic function, renal function and drug interactions are important clinical parameters to consider when selecting patient-centred alternatives to adjusted-dose warfarin.. Several NOACs are now alternatives to warfarin for SSE prevention in NVAF but require providers to make a shift in strategy from tailoring anticoagulant dose based on anticoagulant effect to selection of the anticoagulant based on clinical variables that affect anticoagulant exposure. These variables and their interactions should be considered in choosing an alternative to warfarin and are summarized in a simple table comparing the new anticoagulants.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Humans; Patient-Centered Care; Stroke; Warfarin

The management of cardiomyopathy in pediatric patients is complicated by the risk of cardiac-associated embolism. This review examines the incidence, risk factors, and treatment of embolism in dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), and noncompaction of the left ventricular myocardium (NLVM) in children. The reported incidence of embolism for DCM ranges from 1 to 16%. Left ventricular ejection fraction below 25% or fractional shortening below 15% are major risk factors for intracardiac thrombus formation in this group. The risk of embolism for RCM ranges from 12 to 33%. Atrial dilation is considered the major risk factor. The reported incidence of embolism for NLVM ranges from 0 to 38%, with most studies indicating an absence of detectable thrombus or embolus. Severe systolic dysfunction exacerbates the risk of embolism in this group. On the basis of these risk factors, we propose an algorithm for the management of embolism in these groups of patients.

Topics: Anticoagulants; Aspirin; Cardiomyopathy, Dilated; Cardiomyopathy, Restrictive; Child; Disease Management; Embolism; Humans; Risk Factors; Thrombosis; Ventricular Dysfunction, Left; Ventricular Function, Left; Warfarin

Although oral anticoagulants (OACs) are highly effective in reducing stroke risk in atrial fibrillation, some patients still sustain stroke despite being on an OAC. Our aim was to identify the risk factors that contribute to stroke risk in atrial fibrillation, although patients were taking OACs in a clinical trial setting.. We identified contemporary clinical trials that investigated OACs in patients with atrial fibrillation. Event rates per year from each study and pooled event rates and relative risks, all with a 95% confidence interval, were calculated. Statistical heterogeneity was assessed using the I(2) test.. Six trials were included in the meta-analysis, with a total of 58 883 patients randomized. Characteristics associated with a higher relative risk of stroke while on an OAC included age ≥ 75 years (relative risk, 1.46 [95% confidence interval, 1.25-1.69]), female sex (1.30 [1.15-1.49]), previous stroke/transient ischemic attack (1.85 [1.32-2.60]), vitamin K-antagonist naive status (for vitamin K antagonist experienced, 0.85 [0.74-0.97]), moderate and severe renal impairment (1.54 [1.30-1.81] and 2.22 [1.85-2.66], respectively, compared with normal renal function), previous aspirin use (1.19 [1.04-1.37]), Asian race (1.70 [1.42-2.03]), and a CHADS2 score of ≥ 3 (1.64 [1.18-2.27]).. Stroke rates are higher on OACs with some patient clinical characteristics, that is, older age, female sex, previous stroke/transient ischemic attack, vitamin K-antagonist naive status, renal impairment, previous aspirin use, and higher CHADS2 score. The identified risk factors for stroke while on an OAC could potentially be used to consider a risk assessment tool to flag up high-risk patients while on an OAC (in this case, warfarin). Whether these risk factors apply to novel OACs is uncertain.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Male; Middle Aged; Risk; Risk Assessment; Stroke; Warfarin

For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzimidazoles; Benzylamines; beta-Alanine; Dabigatran; Embolism; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Treatment Outcome; Warfarin

Dabigatran was the first of a new generation of anticoagulation drugs for the indication of non-valvular atrial fibrillation (AF) to be approved. Evidence show that dabigatran 150 mg twice daily significantly reduces the risk of stroke and systemic embolism (RR = 0.65; p < 0.001) and shows a comparable rate of major bleedings (RR = 0.93; p = 0.32), whereas dabigatran 110 mg twice daily was associated with a comparable rate of stroke and systemic embolism (RR = 0.90; p = 0.30) and a significantly lower rate of major bleedings compared to warfarin treatment (RR = 0.80; p = 0.003). The purpose is to review current economic evaluations of these alternatives for healthcare professionals to include these findings in their decision-making.. A systematic literature search identified 43 economic evaluations, of which 10 were included and evaluated according to the Consensus Health Economic Criteria list (CHEC-list) and the Oxford model.. Six economic evaluations concluded that dabigatran was a cost-effective alternative to warfarin. One evaluation concluded the same except when quality in warfarin treatment was excellent, with a mean time in therapeutic range (TTR) > 73%. Three evaluations concluded that dabigatran was a cost-effective alternative to warfarin in patient sub-groups; TTR ≤ 64%, congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack (CHADS2 score) ≥3, or a CHADS2 score = 2 unless international normalized ratio (INR) control was excellent, and with high risk of stroke or in a low-quality warfarin treatment. Dabigatran 110 mg twice daily was in general dominated by dabigatran 150 mg twice daily.. The evaluations were not fully homogeneous, as some did not include loss of productivity, costs of dyspepsia, and annual costs of dabigatran patient management.. In the majority of the economic evaluations, dabigatran is a cost-effective alternative to warfarin treatment. In some evaluations dabigatran is only cost-effective in sub-groups, such as patients with a low TTR-value in warfarin treatment and a CHADS2 score ≥2.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Embolism; Hemorrhage; Humans; Quality-Adjusted Life Years; Stroke; Warfarin

Chronic kidney disease and atrial fibrillation (AF) commonly coexist, and data suggest that renal patients have AF rates in excess of double that encountered in the general population. These patients are at increased risk of stroke, regardless of the presence or absence of AF. Furthermore, a lower GFR causes increased thromboembolic risk in patients with AF - independent of other risk factors. The dilemma facing clinicians treating this cohort of patients is that renal insufficiency confers both a thromboembolic and a bleeding risk. Renal disease also commonly coexists with other risk factors for stroke and bleeding such as hypertension and advanced age. Furthermore, bleeding risk tracks stroke risk and many risk factors are common to both thromboembolism and haemorrhage. Patients with severe renal impairment are also actively excluded from the majority of trials for stroke prevention in AF, including those trials which informed the development of stroke risk factor scoring schemes. Therefore, patients with renal disease and AF present a unique management challenge. The available data suggests that the benefit from warfarin in terms of stroke reduction is not as clear as in the general population, and there is an increased risk of bleeding complications and even ectopic vascular calcification. Thus, it is problematic to extrapolate the benefits of warfarin in the general population to a subgroup that has been actively excluded from clinical trials. The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion. There is a need for large randomised control trials in patients with renal insufficiency and on haemodialysis to provide a bank of high-quality scientific data on which clinicians can base their management decisions. Until then, we must adopt a pragmatic approach which involves careful consideration of the relative risk of stroke and bleeding in each individual patient.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Comorbidity; Dabigatran; Disease Management; Embolism; Female; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension; Intracranial Embolism; Male; Morpholines; Patient Selection; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Risk; Risk Factors; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Warfarin

The direct factor Xa inhibitor apixaban (Eliquis(®)) has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring. This article reviews the efficacy and tolerability of oral apixaban to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial in patients with AF and at least one additional risk factor for stroke, apixaban recipients were significantly less likely than warfarin recipients to experience stroke or systemic embolism, major bleeding or death; the beneficial effects of treatment with apixaban versus warfarin were generally maintained across various patient subgroups. Apixaban recipients also had a significantly lower risk of intracranial haemorrhage than warfarin recipients. In the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients who have Failed or are Unsuitable for Vitamin K Antagonist Therapy) trial in patients with AF and at least one additional risk factor for stroke for whom vitamin K antagonist therapy was unsuitable, apixaban was associated with a significantly lower risk of stroke or systemic embolism than aspirin, without an increase in the risk of major bleeding. In conclusion, although longer-term efficacy and safety data are needed, apixaban is an important new option for use in patients with nonvalvular AF to reduce the risk of stroke or systemic embolism.

Topics: Aspirin; Atrial Fibrillation; Embolism; Fibrinolytic Agents; Humans; Pyrazoles; Pyridones; Stroke; Warfarin

The review analyzes the role of atrial fibrillation concurrent with stable manifestations of coronary heart disease when novel oral anticoagulants are used. It gives the results of comparison of the efficacy and safety of warfarin and rivaroxaban in such patients in the large controlled ROCKET-AF trial.

Topics: Anticoagulants; Atrial Fibrillation; Controlled Clinical Trials as Topic; Embolism; Humans; Morpholines; Rivaroxaban; Thiophenes; Warfarin

Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings.. Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism.. Phase III randomized warfarin-controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all-cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel-Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed-effects (if homogenous) or random-effects models (if heterogeneous).. In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.69-0.98; P = 0.03) and all-cause mortality (RR: 0.91; 95% CI: 0.85-0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74-0.94; P = 0.004) and all-cause mortality (RR: 0.91; 95% CI: 0.84 - 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta-analysis (drug class-outcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41-0.64; P < 0.0001).. Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all-cause mortality. The benefit is largely due to fewer hemorrhagic strokes.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Clinical Trials, Phase III as Topic; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

Dabigatran is a direct inhibitor of thrombin that has recently been approved for primary and secondary stroke prevention and prevention of systemic embolism in patients with atrial fibrillation. The RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy [with Dabigatran Etexilate]) study showed that dabigatran given at a dose of 110 mg twice a day (bid) was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin (International Normalized Ratio target 2.0-3.0), and lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg bid was significantly more effective compared with warfarin and showed a similar rate of major hemorrhages. Both dosages resulted in an approximately 60% to 70% relative reduction of intracranial hemorrhage. The dosage of 110 mg bid should be preferably used in patients older than 75 years at a higher bleeding risk. The Hemoclot (Hyphen BioMed, Mason, OH) test to measure dabigatran serum concentration is commercially available, but presence of the drug may also be detected using the activated partial thromboplastin time or thrombin time.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Embolism; Hemorrhage; Humans; Myocardial Infarction; Stroke; Warfarin

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Embolism; Humans; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Warfarin

This article provides an overview of the clinical profile of oral dabigatran etexilate (Pradaxa®, Pradax™) [hereafter referred to as dabigatran] when used for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF), followed by a review of cost-utility analyses of dabigatran in this patient population. Dabigatran (110 or 150 mg twice daily) demonstrated noninferiority versus adjusted-dose warfarin with regard to the prevention of stroke and systemic embolism (primary endpoint) in patients with AF in the RE-LY trial, and the 150 mg twice-daily dosage was significantly more effective than warfarin for this endpoint, as well as most other efficacy endpoints. The incidence of major bleeding was generally similar in patients receiving dabigatran 150 mg twice daily or warfarin, but was lower in patients receiving dabigatran 110 mg twice daily. With regard to other bleeding endpoints, dabigatran was generally associated with lower rates than warfarin, except for gastrointestinal major bleeding. Dabigatran (both dosages) was associated with a higher incidence of dyspepsia than warfarin. Results of modelled cost-utility analyses from several countries from the perspective of a healthcare payer over a lifetime (or 20-year) time horizon and primarily based on data from the RE-LY trial were generally consistent. All but one analysis demonstrated that twice-daily dabigatran 150 mg (or age-adjusted, sequential dosing) was cost effective with regard to the incremental cost per QALY gained relative to adjusted-dose warfarin in the prevention of stroke and systemic embolism in AF patients, as the results were below generally accepted cost-effectiveness thresholds. In contrast, the incremental cost per QALY gained for dabigatran 110 mg twice daily versus warfarin exceeded cost-effectiveness thresholds in all studies except one. Sensitivity analyses suggested that the cost utility of dabigatran versus warfarin was generally robust to variations in the majority of parameters. However, the incremental cost per QALY gained for dabigatran versus warfarin improved when levels of international normalized ratio control in warfarin recipients decreased and when the baseline level of risk of stroke increased.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Economics, Pharmaceutical; Embolism; Humans; Pyridines; Quality-Adjusted Life Years; Stroke; Warfarin

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

Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis.. Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS).. Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE [OR 0.64 (0.44, 0.94], P=0.02]. Compared to warfarin, NOA were associated with a significantly reduced risk of HS [OR 0.43 (0.34, 0.55), P<0.001, NNT to avoid a HS 153] and all cause death [OR 0.90 [0.84, 0.96], P=0.03, NNT to save one fatality 43]. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps>0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA.. Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Biological Availability; Comparative Effectiveness Research; Dabigatran; Drug Monitoring; Embolism; Female; Humans; Male; Middle Aged; Morpholines; Outcome and Process Assessment, Health Care; Pharmacovigilance; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Stroke; Thiophenes; Warfarin

The objective of this review is to summarize data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trials of apixaban for stroke prevention in patients with atrial fibrillation (AF). The ARISTOTLE trial compared apixaban with warfarin in 18 201 patients with AF and ≥ 1 additional risk factor for stroke. The AVERROES trial compared apixaban with aspirin in 5599 patients with AF who were at increased risk of stroke and for whom vitamin K antagonists were unsuitable. In ARISTOTLE, apixaban reduced the risk of stroke or systemic embolism by 21% compared with warfarin (1.27% vs 1.60% per year; hazard ratio, 0.79; 95% confidence interval, 0.66-0.95). The reduction was significant and demonstrated the superiority of apixaban over warfarin for the primary outcome of preventing stroke or systemic embolism (P = 0.01 for superiority). Apixaban also reduced all-cause mortality by 11% (P = 0.047) and major bleeding by 31% (P < 0.001) compared with warfarin. The benefits of apixaban observed in ARISTOTLE are further supported by the results from AVERROES, which demonstrated a 55% reduction in the risk of stroke or systemic embolism compared with aspirin. Risk of major bleeding was not significantly different between apixaban and aspirin. Subgroup analyses in both trials demonstrated that the effects of apixaban are highly consistent across various patient subpopulations. Discontinuation of study medication was significantly lower with apixaban than with either warfarin in ARISTOTLE or aspirin in AVERROES. Apixaban is the first new oral anticoagulant that has been shown to be superior to warfarin in reducing stroke or systemic embolism, all-cause mortality, and major bleeding in patients with AF. Moreover, in patients with AF who are considered unsuitable for warfarin therapy, apixaban was more effective than aspirin for stroke prevention and had a similar rate of major bleeding.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Humans; Pyrazoles; Pyridones; Risk Factors; Stroke; Warfarin

Acute renal artery embolism is an uncommon clinical diagnosis. We present a case report of a patient who was treated with transcatheter thrombolysis and a literature review and discussion of this condition and its management.

Topics: Abdomen, Acute; Acute Disease; Anticoagulants; Embolism; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Radiography; Renal Artery Obstruction; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Vascular Patency; Warfarin

Warfarin for stroke prevention in patients with atrial fibrillation (AF) is well documented. However, it has not been examined in the prevention of systemic embolism.. To evaluate the efficacy of warfarin in preventing systemic embolism (embolism to limbs or viscera) in patients with AF.. A combined Medline, Embase, Cochrane Library and SveMed+ search were made. Fifteen studies were included. Warfarin was better than antiplatelet agents for preventing systemic embolism with a 50% reduction of risk (odds ratio (OR) = 0.50, 95% CI 0.33 to 0.75) without increasing the risk of major bleeding (OR = 1.07; 95% CI 0.85 to 1.34). Warfarin compared with placebo resulted in a risk reduction of 71% (OR = 0.29; 95% CI 0.08 to 1.07) with higher risk of major bleeding with warfarin (OR = 3.01; 95% CI 1.31 to 6.92). Results of a comparison of warfarin with low-dose warfarin (OR = 1.52; 95% CI 0.40 to 5.81) or low-dose warfarin with aspirin (OR = 1.00; 95% CI 0.17 to 5.81) were inconclusive.. Warfarin not only reduces the risk of stroke but is also better than placebo and antiplatelet agents in prevention of systemic embolism in patients with non-valvular AF. Warfarin increases the risk of major bleeding compared with placebo but not compared with antiplatelet agents.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Embolism; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Warfarin; Young Adult

Renal artery embolism was first described in 1940, but it is only recently becoming recognized as a clinically significant entity. Although relatively uncommon, it is clearly responsible for considerable morbidity in patients who experience it. The pathogenesis is typically related to cardiac thrombus formation with subsequent embolization, although other etiologies have been described. The authors present a case report followed by a review of the literature to highlight the clinical characteristics of this phenomena. Presentation, diagnostics, and treatment options will be reviewed with the aim of increasing awareness of renal artery embolism. As clinicians become more familiar with this condition, they will be more likely to consider it as a possible diagnosis in patients with a typical presentation. This will hopefully lead to improved care through prompt diagnosis and treatment, particularly as one treatment option may be time sensitive.

Topics: Aged; Aged, 80 and over; Anticoagulants; Biomarkers; Embolism; Female; Flank Pain; Heparin; Humans; Kidney Function Tests; Magnetic Resonance Imaging; Male; Radiography; Renal Artery Obstruction; Ultrasonics; Warfarin

Deep vein thrombosis and its lethal complication pulmonary embolism are manifestations of venous thromboembolism (VTE), which is typically associated with cancer and recent major surgery. Certain solid tumors and hematologic malignancies impose an inherently elevated risk of VTE that is compounded by chemotherapy and other risk factors. Multiple myeloma (MM) and other plasma cell dyscrasias are thrombogenic as a consequence of their multiple hemostatic effects, including elevated interleukin-6 levels, pro-coagulant antibody formation, paraprotein interference with fibrin structure, activated protein C resistance, and endothelial damage. The oral immunomodulatory drugs thalidomide and lenalidomide have produced major therapeutic responses in patients with MM when used in combination with oral steroids and chemotherapy, but a high incidence of VTE has been reported. Various VTE prophylaxis strategies with thalidomide- and lenalidomide-containing combinations have been investigated in clinical studies. This review discusses emerging results on the use of VTE prophylaxis to minimize VTE risks associated with MM treatment regimens containing thalidomide and lenalidomide.

Topics: Anticoagulants; Aspirin; Clinical Trials as Topic; Drug Therapy, Combination; Embolism; Factor V; Heparin, Low-Molecular-Weight; Humans; Immunologic Factors; Multiple Myeloma; Mutation; Prothrombin; Risk Reduction Behavior; Treatment Outcome; Venous Thrombosis; Warfarin

Atrial fibrillation is the most frequently encountered tachyarrhythmia requiring therapy. Treatment issues include therapy for any reversible cause; the identification and treatment of any underlying structural disorder; control of the ventricular rate, both for symptom reduction and prevention of tachycardic-induced cardiomyopathy; restoration and maintenance of sinus rhythm when symptoms persist despite rhythm control; and anticoagulation in patients with high-risk markers for systemic embolization: age over 65 years, hypertension, diabetes, ventricular failure, rheumatic valvular disease, and prior stroke or other embolic event. In such patients, anticoagulation with warfarin is currently recommended. Warfarin therapy carries significant risks (especially bleeding), inconveniences (the cost of prothrombin time monitoring, the need for rigid dietary stability, the concerns of drug and herbal interactions), and other concerns (the issue of generic formulation substitution).. Under development are oral thrombin inhibitors. The first to reach clinical approval will likely be ximelagatran. In clinical trials to date, ximelagatran has proven to be equal to or superior to warfarin in the prevention and treatment of thrombophlebitis. In atrial fibrillation patients, the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) trials completed so far appear to show a similar or better efficacy for ximelagatran versus warfarin as regards both prevention of embolic events and lower risks of major bleeding, with no serious adverse effects except for apparently reversible alterations in liver function tests in approximately 6% of subjects, all occurring early in therapy to date. If the remaining SPORTIF trial (SPORTIF V) is confirmatory (results to be available in late 2003), it is expected that this exciting new product will be submitted this winter to the Food and Drug Administration for approval. Recent findings also include the observations in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control Versus Electrical Cardioversion (RACE) trials that anticoagulation should not be discontinued despite the restoration and maintenance of sinus rhythm.. Oral direct thrombin inhibitors, such as ximelagatran, appear likely to replace the use of warfarin in most patients in the near future, because of a better risk-benefit profile.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials as Topic; Embolism; Fibrinolytic Agents; Humans; Prothrombin Time; Randomized Controlled Trials as Topic; Stroke; Venous Thrombosis; Warfarin

A 56-year-old man presented with sustained chest pain. Coronary angiography revealed total occlusion of the distal right coronary artery and left anterior descending branch. Left ventriculography depicted a mobile mass in the right sinus of Valsalva originating from the ostium of the right coronary artery. Transesophageal echocardiography (TEE) showed a mobile mass in the sinus of Valsalva and another mobile mass in the aortic arch. The mass at the right sinus of Valsalva was surgically resected, and histologic examination revealed an organized thrombus. Coagulation study showed protein S deficiency. This is the first case of acute myocardial infarction as a result of multiple coronary embolism caused by thrombosis in the right sinus of Valsalva with a second aortic arch thrombosis, contributed by protein S deficiency.

Topics: Anticoagulants; Coronary Angiography; Coronary Thrombosis; Echocardiography, Transesophageal; Embolism; Humans; Male; Middle Aged; Myocardial Infarction; Sinus of Valsalva; Warfarin

Intracardiac thrombosis and cardioembolisms may have impressive effects on quality of life, prognosis and therapeutic costs in patients with valve disease or replacement devices. Distinct pathophysiological differences exist regarding intracardiac thrombus formation in low-versus high-pressure areas. Important cardiac confounders for low-pressure areas are left atrial geometry and function, including atrial fibrillation or loss of active atrial contraction. In high-pressure areas, flow velocity and shear stress are raised, and this may result in flow turbulence, for example when blood passes a stenotic area. Other major factors which correlate with intracardiac thrombus formation are implantation of polymer material and the degree of endocardial damage resulting for example, from infective or rheumatic endocarditis. Because of the interaction of platelets and the plasma clotting system, a combination of oral anticoagulation therapy and antiplatelet drugs should prevent more thromboembolic events than might anticoagulation alone. Recent studies in patients with prosthetic heart valves have indicated a positive risk-benefit profile if low-dose antiplatelet drugs are added to moderate intensive oral anticoagulation therapy. Thromboembolic events and bleeding complications due to oral anticoagulation therapy are accepted key parameters to demonstrate the superiority of one replacement device over another. However, there is no consistent system for reporting morbid events. In order to organize low and narrow target INR ranges, point-of-care patient self-testing modalities have been introduced and used effectively in large sample sizes. In the near future, some promising new drugs--including direct thrombin or factor Xa inhibitors with broader therapeutic ranges and thus fewer side effects--will become available. The test for these drugs will be their potential to prevent intracardiac thrombosis and cardioembolism in a patient population which is under significant risk.

Topics: Anticoagulants; Coronary Thrombosis; Drug Therapy, Combination; Embolism; Heart Valve Diseases; Humans; Platelet Aggregation Inhibitors; Thrombolytic Therapy; Warfarin

Topics: Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Echocardiography, Transesophageal; Embolism; Humans; Middle Aged; Practice Guidelines as Topic; Warfarin

The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) trial compared cardioversion following transesophageal echocardiography (TEE) against conventional management of atrial fibrillation (ie, cardioversion following 3 weeks of anticoagulation) in patients scheduled to undergo electrical cardioversion.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Protocols; Combined Modality Therapy; Decision Trees; Echocardiography, Transesophageal; Electric Countershock; Embolism; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Thrombosis; Time Factors; Warfarin

Thrombosis and the complicating emboli that can result are important causes of illness and death. Thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined. Agents such as heparin, low-molecular weight heparin, warfarin, aspirin, ticlopidine, clopidogrel, and tirofiban are used to prevent venous or arterial thrombosis. Patients taking these antithrombotic agents may be at risk for excessive bleeding after invasive dental procedures. The current antithrombotic agents used in medicine are reviewed, and the dental management of patients taking these agents is discussed.

Topics: Anticoagulants; Aspirin; Blood Coagulation Tests; Clopidogrel; Dental Care; Drug Interactions; Embolism; Fibrinolytic Agents; Hemostasis; Heparin; Heparin, Low-Molecular-Weight; Humans; Oral Hemorrhage; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombosis; Ticlopidine; Tirofiban; Tyrosine; Venous Thrombosis; Warfarin

Because of its prevalence in the population and its associated underlying diseases and morbidity, atrial fibrillation (AF) is an important and costly health problem. Advancing age, diabetes, heart failure, valvular disease, hypertension, and myocardial infarction predict the occurrence of AF within a population. The management of AF is complex and involves prevention of thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke occurs in 4.5% of untreated patients with AF per year. Independent risk factors for stroke in nonrheumatic patients with AF are advanced age; a history of prior embolism, hypertension, or diabetes; and echocardiographic findings of left atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by two-thirds and death by one-third; aspirin is only about half as effective overall and is insufficient therapy for those with risk factors for stroke. Options for thromboembolic prophylaxis are use of warfarin for all in whom it is safe or, alternatively, warfarin for those with risk factors and aspirin for those without risk factors. One-half of the patients with AF are 75 years of age or older. The uniform applicability and relative safety of warfarin therapy in this age-group are controversial. Specific therapy for the arrhythmia should be dictated by the need to control symptoms. Symptomatic treatments include rate-control medications and strategies designed to terminate and prevent arrhythmia recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow excessive ventricular rates in patients with AF and may favorably manage comorbid conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per year in preventing recurrences of AF, and these agents, except amiodarone, may increase the risk of sudden death in patients with certain types of organic heart disease and AF. The use of nonpharmacologic symptomatic therapies such as atrioventricular node modification or ablation with a rate-response pacemaker or surgical intervention is increasing.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Anti-Arrhythmia Agents; Aspirin; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Diabetes Complications; Digoxin; Diltiazem; Embolism; Humans; Hypertension; Thromboembolism; Verapamil; Warfarin

Anticoagulation with warfarin has been shown to be effective in preventing ischemic stroke in patients with atrial fibrillation. However, physicians have been reluctant to prescribe this therapy for patients age 60 and older because of the associated risk of bleeding during antithrombotic therapy. Four clinical features independently increase the risk of stroke in individuals with atrial fibrillation: previous stroke or transient ischemic attack, diabetes, history of hypertension, and advancing age. In individual patients, bleeding complications can be reduced by eliminating loading doses, monitoring therapy frequently during the initiation phase, targeting lower INRs, recognizing the potential for drug interactions, and identifying clinical risk factors.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Embolism; Heart; Humans; Middle Aged; Risk Factors; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Embolism; Fibrinolytic Agents; Hemorrhage; Humans; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Deep venous thrombosis (DVT) is responsible for approximately 200,000 hospitalizations annually in the United States. DVT is easier and less expensive to prevent than to diagnose and treat. For every one million patients undergoing surgery who do receive prophylaxis against venous thrombosis, approximately $60 million will be saved in direct health care costs because effective mechanical and pharmacologic modalities are available to prevent most venous thrombi. The therapy for DVT should be based upon the anatomic extent of the thrombus as well as upon the patient's risk for pulmonary embolism, recurrent DVT, and chronic venous insufficiency. In patients with paradoxical embolism, a patent foramen ovale, occult leg vein thrombosis (particularly isolated calf vein thrombosis) is frequently present.

Topics: Animals; Anticoagulants; Embolism; Female; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Premedication; Thrombolytic Therapy; Thrombophlebitis; Warfarin

A 1987 survey of U.S. orthopedic surgeons found that 84% used some form of DVT prophylaxis. Ten percent used prophylaxis only for their "high-risk patients," and 6% never used prophylaxis. Twenty percent of the surgeons had at least one THR patient die from a fatal PE in the last five years. Fifty percent of the surgeons using warfarin had subsequently discontinued its use because of bleeding complications and monitoring difficulties. Compared with a survey done 13 years previously, this recent study showed a dramatic rise in the number of surgeons using DVT prophylaxis. The majority, however, were using methods that are ineffective: 67% used aspirin and 17% used fixed doses of subcutaneous heparin. Because the incidences of DVT and PE in THR patients are high, all of these patients should receive prophylaxis. The standard LDH regimen, effective for patients receiving gynecologic, general, and most orthopedic procedures, is ineffective for THR patients. The available prophylactic methods proven to reduce DVT and PE in THR patients are adjusted-dose subcutaneous heparin, dextrans, low-dose warfarin, and EPC. Comparative studies have not clearly demonstrated superiority of any one method. However, low-dose warfarin may offer better protection in very high-risk patients. External pneumatic compression offers protection without increasing bleeding risks. Dextrans are effective but are expensive and may be associated with significant side effects. Adjusted-dose subcutaneous heparin is also effective but is cumbersome to use. Low-molecular-weight heparin appears to be a promising alternative. We recommend the routine use of EPC and reserve low-dose warfarin fro patients with histories of prior thromboembolic or venous disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bandages; Dextrans; Embolism; Heparin; Hip Prosthesis; Humans; Postoperative Care; Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebral Infarction; Chronic Disease; Clinical Trials as Topic; Embolism; Fibrinolytic Agents; Humans; Middle Aged; Warfarin

Topics: Administration, Oral; Embolism; Humans; Thrombosis; Warfarin

Topics: Aspirin; Atrial Fibrillation; Embolism; Heart Diseases; Humans; Thrombolytic Therapy; Warfarin

The sudden development of cyanotic lesions on the feet may be a result of atheroembolic disease or a number of medical conditions. A careful history and physical examination, basic laboratory tests, and noninvasive vascular assessment usually distinguish between medical and surgical causes and direct the choice of further investigations. Specific therapy is often available for medical conditions causing this syndrome. The management of atheroembolic disease is more controversial. In particular, further research is necessary to determine which patients need surgical intervention and which patients can be managed safely by medical therapy.

Topics: Adrenal Cortex Hormones; Blood Coagulation Disorders; Calcinosis; Cyanosis; Embolism; Humans; Ischemia; Postoperative Complications; Skin Diseases; Syndrome; Toes; Vasculitis; Warfarin

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Therapy, Combination; Embolism; Humans; Meta-Analysis as Topic; Research Design; Warfarin

A man aged 50 presented with a history of a cerebrovascular accident and arterial embolism at two discrete peripheral sites. Echocardiography showed thrombus trapped in an interatrial site and impending paradoxical embolism was diagnosed. Treatment with heparin was started and the potentially embolic intracardiac material was removed at open heart surgery. The patient was treated with warfarin and made a good recovery. This is only the third case report of impending paradoxical embolism diagnosed in life.

Topics: Echocardiography; Embolism; Heart Septal Defects, Atrial; Humans; Male; Middle Aged; Warfarin

The long-term use of oral anticoagulants like warfarin in artery disease has long been controversial. Possible aims of treatment include the primary or secondary prevention of systemic embolism, preventing recurrence after myocardial infarction or the progression of transient cerebral ischemia to a complete stroke, and the prevention of artery graft occlusion. The value of long-term anticoagulation is generally accepted in the few situations where, as in patients with mechanical heart valve prostheses, mitral valve disease and atrial fibrillation, or idiopathic dilated cardiomyopathy, the risk of arterial thromboembolism without anticoagulation is known to be high and there is good evidence that anticoagulants are effective, so the benefit:risk balance strongly favours their use. In many settings, however, it is hard to justify long-term warfarin treatment as the benefit:risk balance remains unknown; either because the risk of thromboembolism without anticoagulation remains to be clearly defined (as in the case of patients with 'lone' atrial fibrillation), or because possible benefits have not been well documented (as after transient cerebral ischemia or peripheral vascular surgery). Finally, there is the difficult problem of estimating the benefit from long-term anticoagulation after myocardial infarction. It seems that warfarin can reduce the likelihood of non-fatal reinfarction with relative safety in highly selected patients, but whether it reduces mortality, and how its effect compares with that of other, more recent, therapies aimed at preventing reinfarction, remains unknown.

Topics: Cerebrovascular Disorders; Embolism; Humans; Myocardial Infarction; Vascular Diseases; Warfarin

Approximately 20,000 heart valve prostheses are inserted yearly in the United States. Even after successful heart operations, the patients who receive them cannot be regarded as healthy individuals but are a special group with special problems who need close medical attention for the rest of their lives. They are susceptible to many unusual complications because of their implanted foreign body, and it is a challenge to all physicians in contact with them to be aware of their peculiar problems in order to prevent complications if possible and to treat them immediately if they occur. General therapy, surgical complications, infection, and mechanical problems are reviewed, with means for management outlined. These difficulties can be dealt with only by careful follow-up and well-coordinated teamwork between the family physician and the institution where the operation was performed.

Topics: Activities of Daily Living; Anti-Arrhythmia Agents; Diet, Sodium-Restricted; Digitalis Glycosides; Diuretics; Embolism; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Postoperative Care; Postoperative Complications; Thrombosis; Time Factors; Warfarin

Topics: Animals; Blood Coagulation; Capillaries; Embolism; Heparin; Humans; Immunotherapy; Lung Neoplasms; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Neoplastic Cells, Circulating; Thrombin; Warfarin

Topics: Barbiturates; Biotransformation; Depression, Chemical; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance; Embolism; Enzyme Induction; Hemorrhage; Humans; Liver; Male; Middle Aged; Thrombosis; Vitamin K; Warfarin

Topics: Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Embolism; Factor IX; Factor VII; Factor X; Heparin; Humans; Myocardial Infarction; Prothrombin; Prothrombin Time; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Vitamin K; Warfarin

The neutrophil-to-lymphocyte ratio (NLR) is the ratio between neutrophil and lymphocyte counts measured in peripheral blood. NLR is easily calculable based on a routine blood test available worldwide and may reflect systemic inflammation. However, the relationship between NLR and clinical outcomes in atrial fibrillation (AF) patients is not well-described.. We calculated NLR at baseline in ENGAGE AF-TIMI 48, a randomized trial comparing edoxaban versus warfarin in patients with AF followed for 2.8 years (median). The association of baseline NLR with major bleeding events, major adverse cardiac events (MACE), cardiovascular death, stroke/systemic embolism, and all-cause mortality were calculated.. The median baseline NLR in 19,697 patients was 2.53 (interquartile range 1.89-3.41). NLR was associated with major bleeding events (HR 1.60; 95% CI 1.41-1.80), stroke/systemic embolism (HR 1.25; 95% CI, 1.09-1.44), MI (HR 1.73; 95% CI 1.41-2.12), MACE (HR 1.70; 95% CI 1.56-1.84), CV (HR 1.93; 95% CI 1.74-2.13) and all-cause mortality (HR 2.00; 95% CI 1.83-2.18). The relationships between NLR and outcomes remained significant after adjustment for risk factors. Edoxaban consistently reduced major bleeding. MACE, and CV death across NLR groups vs. warfarin.. NLR represents a widely available, simple, arithmetic calculation that could be immediately and automatically reported during a white blood cell differential measurement to identify patients with AF at increased risk of bleeding, CV events, and mortality.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Lymphocytes; Neutrophils; Stroke; Treatment Outcome; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Medicare; Stroke; Treatment Outcome; United States; Warfarin

In patients with atrial fibrillation (AF), peripheral artery disease (PAD) is associated with higher rates of stroke and bleeding. Both higher dose edoxaban (60/30 mg) and lower dose edoxaban (30/15 mg) were non-inferior to warfarin for stroke and systemic embolism (SSE) and significantly reduced major bleeding in AF patients in the global study to assess the safety and effectiveness of edoxaban vs standard practice of dosing with warfarin in patients with atrial fibrillation (ENGAGE AF-TIMI 48) trial. Whether the efficacy and safety of these dosing strategies vs. warfarin are consistent in patients with AF and PAD has not been described.. Of 21 105 patients with AF randomized to warfarin, edoxaban 60/30 mg, or edoxaban 30/15 mg, 841 were identified with PAD. Endpoints included major adverse cardiovascular events (MACEs), SSE, and major bleeding. Patients with PAD had higher risk of MACEs [adjusted hazard ratio (HRadj) 1.33, 95% confidence interval (CI) 1.12-1.57, P = 0.001] and cardiovascular (CV) death (HRadj 1.49, 95% CI 1.21-1.83, P < 0.001) than those without PAD, but not major bleeding. The efficacy of edoxaban 60/30 mg vs. warfarin was consistent regardless of PAD (SSE HR; PAD 1.16, 95% CI 0.42-3.20; no-PAD 0.86, 95% CI 0.74-1.02, P-interaction 0.57) as was major bleeding (PAD 0.96, 95% CI 0.54-1.70; no-PAD 0.80, 95% CI 0.70-0.91, P-interaction 0.54). Edoxaban 30/15 mg was inferior for SSE, with significant heterogeneity when stratified by PAD status (P-interaction 0.039).. Patients with AF and PAD are at heightened risk of MACEs and CV death vs. those without PAD. The efficacy and safety of edoxaban 60/30 mg vs. warfarin in AF are consistent regardless of PAD; however, edoxaban 30/15 mg is inferior for stroke prevention in AF patients with PAD. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00781391.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Peripheral Arterial Disease; Pyridines; Stroke; Thiazoles; Warfarin

Long-term use of oral anticoagulants (OACs) is necessary for stroke prevention in patients with atrial fibrillation (AF). The effectiveness and safety of OACs in extremely older patients (ie, aged 80 years or older) with AF and at high risk of bleeding needs to be elucidated.. To examine the effects of very low-dose edoxaban (15 mg) vs placebo across 3 age strata (80-84 years, 85-89 years, and ≥90 years) among patients with AF who were a part of the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial.. This prespecified subanalysis of a phase 3, randomized, double-blind, placebo-controlled trial was conducted from August 5, 2016, to December 27, 2019. Patients with AF aged 80 years or older who were not considered candidates for standard-dose OACs were included in the study; reasons these patients could not take standard-dose OACs included low creatinine clearance (<30 mL per minute), low body weight (≤45 kg), history of bleeding from critical organs, continuous use of nonsteroidal anti-inflammatory drugs, or concomitant use of antiplatelet drugs. Eligible patients were recruited randomly from 164 hospitals in Japan and were randomly assigned 1:1 to edoxaban or placebo.. Edoxaban (15 mg once daily) or placebo.. The primary efficacy end point was the composite of stroke or systemic embolism. The primary safety end point was International Society on Thrombosis and Hemostasis-defined major bleeding.. A total of 984 patients (mean [SD] age: age group 80-84 years, 82.2 [1.4] years; age group 85-89 years, 86.8 [1.4] years; age group ≥90 years, 92.3 [2.1] years; 565 women [57.4%]) were included in this study. In the placebo group, estimated (SE) event rates for stroke or systemic embolism increased with age and were 3.9% (1.2%) per patient-year in the group aged 80 to 84 years (n = 181), 7.3% (1.7%) per patient-year in the group aged 85 to 89 years (n = 184), and 10.1% (2.5%) per patient-year in the group aged 90 years or older (n = 127). A 15-mg dose of edoxaban consistently decreased the event rates for stroke or systemic embolism with no interaction with age (80-84 years, hazard ratio [HR], 0.41; 95% CI, 0.13-1.31; P = .13; 85-89 years, HR, 0.42; 95% CI, 0.17-0.99; P = .05; ≥90 years, HR, 0.23; 95% CI, 0.08-0.68; P = .008; interaction P = .65). Major bleeding and major or clinically relevant nonmajor bleeding events were numerically higher with edoxaban, but the differences did not reach statistical significance, and there was no interaction with age. There was no difference in the event rate for all-cause death between the edoxaban and placebo groups in all age strata.. Results of this subanalysis of the ELDERCARE-AF randomized clinical trial revealed that among Japanese patients aged 80 years or older with AF who were not considered candidates for standard OACs, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism consistently across all 3 age strata, including those aged 90 years or older, albeit with a higher but nonstatistically significant incidence of bleeding.. ClinicalTrials.gov Identifier: NCT02801669.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Pyridines; Stroke; Thiazoles; Warfarin

There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF).. The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA. From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event.. There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis.. URL: https://www.. gov; Unique identifier: NCT02942407.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis; Stroke; Treatment Outcome; Warfarin

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Topics: Administration, Oral; Aspirin; Atrial Fibrillation; Atrial Flutter; Bioprosthesis; Brazil; Cause of Death; Creatinine; Embolism; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Mitral Valve; Rivaroxaban; Sample Size; Stroke; Surgical Procedures, Operative; Thrombosis; Treatment Outcome; Warfarin

To date, vitamin K antagonists are the only available oral anticoagulants in patients with mechanical heart valves. In this way, we developed a pilot trial with rivaroxaban..  The RIWA study was a proof-of-concept, open-label, randomized clinical trial and was designed to assess the incidence of thromboembolic and bleeding events of the rivaroxaban-based strategy (15 mg twice daily) in comparison to dose-adjusted warfarin. Patients were randomly assigned in a 1:1 ratio and were followed prospectively for 90 days..  A total of 72 patients were enrolled in the present study. Of these, 44 patients were randomized: 23 patients were allocated to the rivaroxaban group and 21 to the warfarin group. After 90 days of follow-up, the primary outcome occurred in one patient (4.3%) in the rivaroxaban group and three patients (14.3%) in the warfarin group (risk ratio [RR] 0.27; 95% confidence interval [CI] 0.02-2.85; P = 0.25). Minor bleeding (without discontinuation of medical therapy) occurred in six patients (26.1%) in the rivaroxaban group versus six patients (28.6%) in the warfarin group (RR 0.88; 95% CI 0.23-3.32; P = 0.85). One patient in the warfarin group died from myocardial infarction. No cases of hemorrhagic stroke, valve thrombosis, peripheral embolic events, or new intracardiac thrombus were related in both groups.. In this pilot study, rivaroxaban 15 mg twice daily had thromboembolic and bleeding events similar to warfarin in patients with mechanical heart valves. These data confirm the authors' proof-of-concept and suggest that a larger trial with a similar design is not unreasonable. CLINICALTRIAL.. NCT03566303.

Topics: Adult; Brain Infarction; Dose-Response Relationship, Drug; Embolism; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Pilot Projects; Rivaroxaban; Stroke; Thromboembolism; Warfarin

ROCKET AF demonstrated the efficacy and safety of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). We examined baseline characteristics and outcomes in patients enrolled in Latin America compared with the rest of the world (ROW).. ROCKET AF enrolled 14,264 patients from 45 countries. Of these, 1,878 (13.2%) were from 7 Latin American countries. The clinical characteristics and outcomes (adjusted by baseline characteristics) of these patients were compared with 12,293 patients from the ROW. Treatment outcomes of rivaroxaban compared with warfarin were also stratified by region.. The annual rate of stroke/SE was similar in those from Latin American and ROW (P= .63), but all-cause and vascular death were significantly higher than in ROW (HR 1.40, 95% CI 1.20-1.64; HR 1.38, 95% CI 1.14-1.68; P< .001). Rates of major or nonmajor clinically relevant bleeding tended to be lower in Latin America (HR 0.89, 95% CI 0.80-1.0; P= .05). Rates of stroke and/or SE were similar with rivaroxaban and warfarin in patients from Latin America and ROW (HR 0.83, 95% CI 0.54-1.29 vs HR 0.89, 95% CI 0.75-1.07; interaction P= .77).. Patients with AF in Latin America had similar rates of stroke and/or SE, higher rates of vascular death, and lower rates of bleeding compared with patients in the ROW. The effect of rivaroxaban compared with warfarin in Latin America was similar to the ROW. Further studies analyzing patient- and country-specific determinants of these regional differences in Latin America are warranted.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Latin America; Male; Mortality; Risk Assessment; Rivaroxaban; Stroke; Treatment Outcome; 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

Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.. In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.. Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.

Topics: Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Multimorbidity; Polypharmacy; Pyrazoles; Pyridones; Stroke; Warfarin

To investigate the relationship between body mass index (BMI) and outcomes in patients with atrial fibrillation (AF).. In the ENGAGE AF-TIMI 48 trial, patients with AF were randomized to warfarin (international normalized ratio 2.0-3.0) or edoxaban. The cohort (N = 21 028) included patients across BMI categories (kg/m2): underweight (<18.5) in 0.8%, normal (18.5 to <25) in 21.4%, overweight (25 to <30) in 37.6%, moderately obese (30 to <35) in 24.8%, severely obese (35 to <40) in 10.0%, and very severely obese (≥40) in 5.5%. In an adjusted analysis, higher BMI (continuous, per 5 kg/m2 increase) was significantly and independently associated with lower risks of stroke/systemic embolic event (SEE) [hazard ratio (HR) 0.88, P = 0.0001], ischaemic stroke/SEE (HR 0.87, P < 0.0001), and death (HR 0.91, P < 0.0001), but with increased risks of major (HR 1.06, P = 0.025) and major or clinically relevant non-major bleeding (HR 1.05, P = 0.0007). There was a significant interaction between sex and increasing BMI category, with lower risk of ischaemic stroke/SEE in males and increased risk of bleeding in women. Trough edoxaban concentration and anti-Factor Xa activity were similar across BMI groups >18.5 kg/m2, while time in therapeutic range for warfarin improved significantly as BMI increased (P < 0.0001). The effects of edoxaban vs. warfarin on stroke/SEE, major bleeding, and net clinical outcome were similar across BMI groups.. An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding. The efficacy and safety profiles of edoxaban were similar across BMI categories ranging from 18.5 to >40.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Obesity; Overweight; Proportional Hazards Models; Pyridines; Stroke; Thiazoles; Treatment Outcome; Warfarin

Warfarin is dependent on multiple hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 metabolism. The aim of this analysis was to assess the impact of interacting medication use on the treatment effects of apixaban versus warfarin. Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications at randomization in ARISTOTLE (n = 18,201). Interacting medications for apixaban were identified as combined P-gp and 3A4 inhibitors or inducers while interacting medications for warfarin were defined as those highly probable for warfarin potentiation or inhibition. At randomization, 5547 (30.5%) patients were on an interacting medication, including 2722 on apixaban and 2825 on warfarin. Patients using an interacting medication were more likely to be female, taking aspirin, and have a history of prior bleeding and were less likely to have a prior stroke or transient ischemic attack. No significant differences were observed on the treatment effect of apixaban compared with warfarin in patients on and off interacting medications for outcomes including the primary efficacy outcome of stroke or systemic embolism (P for interaction = 0.79) or the primary safety outcome of major bleeding (P for interaction = 0.75). Use of interacting medications with anticoagulants occurs often in patients with atrial fibrillation. Despite the potential for altered exposure, interacting medication use was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in the ARISTOTLE trial.Trial registration ClinicalTrials.gov, NCT00412984.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Drug Interactions; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Stroke; Treatment Outcome; Warfarin; Young Adult

Uninterrupted dabigatran therapy reduces stroke risk in patients with nonvalvular atrial fibrillation (NVAF) undergoing ablation and is associated with a lower bleeding risk than uninterrupted warfarin therapy. Minimally interrupted direct oral anticoagulant therapy is widely used, but data from controlled studies are insufficient.. To compare the safety and efficacy of minimally interrupted dabigatran vs uninterrupted warfarin therapy in patients undergoing catheter ablation for NVAF.. The ABRIDGE-J (ABlation peRIoperative DabiGatran in use Envisioning in Japan) trial is a open-label, randomized clinical trial performed in 28 Japanese treatment centers. A total of 504 patients scheduled for NVAF ablation were enrolled; 500 were randomized to the study treatments; 499 received at least 1 dose of dabigatran etexilate (n = 248) or warfarin potassium (n = 251); and 442 underwent ablation (220 in the dabigatran group and 222 in the warfarin group). Data were collected from May 1, 2014, through September 14, 2015, and analyzed from March 7, 2017, through January 28, 2019.. Appropriate dose anticoagulation was administered 4 weeks before and at least 3 months after ablation in all patients. Dabigatran therapy was interrupted before catheter ablation (holding of 1-2 doses) and resumed after ablation.. Primary end points were the incidence of embolism during the perioperative period and atrial thrombus just before the ablation. The main secondary end point was the incidence of major bleeding events until 3 months after ablation.. Of the 442 patients who underwent ablation, 74.9% were men and the median age was 66 years (interquartile range, 59-71 years). Before ablation, 1 cerebral infarction and 1 thrombus in the left atrium occurred in the warfarin group, but no events occurred in the interrupted dabigatran group. After ablation, the mean (SD) incidence of major bleeding events was significantly lower with dabigatran (3 patients [1.4% {0.8%}; 95% CI, 0.4%-4.2%]) vs warfarin (11 patients [5.0% {1.5%}; 95% CI, 2.8%-8.8%]; P = .03). No thromboembolic events occurred after ablation in the dabigatran group; 1 (0.5%) occurred in the warfarin group.. In patients undergoing ablation for NVAF, anticoagulation with minimally interrupted dabigatran therapy did not increase thromboembolic events and was associated with fewer bleeding complications than uninterrupted warfarin therapy.. umin.ac.jp Identifier: UMIN000013129.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Embolism; Female; Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Perioperative Period; Prospective Studies; Thromboembolism; Treatment Outcome; Warfarin

Atrial fibrillation (AF) increases risk of stroke 5-fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD.. Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke.. This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]).. A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66-1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88-1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64).. Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Carotid Artery Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

There is limited information about the use of antithrombotic therapies and outcomes of Latin American (LatAm) subjects with atrial fibrillation. The global ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial compared the efficacy and safety of edoxaban versus warfarin over a median follow-up of 2.8 years.. The authors aimed to compare adjusted outcomes in Latin America versus outside Latin America and to compare outcomes stratified by anticoagulant treatment and region.. The authors analyzed clinical characteristics and outcomes, adjusted for baseline characteristics, the Human Development Index, and randomized treatment of 2,661 LatAm versus 18,444 non-Latin American subjects (nLAS).. After multivariable adjustment, LatAm subjects with atrial fibrillation had higher rates of intracranial hemorrhage and death than nLAS. Outcomes with higher-dose edoxaban versus warfarin were at least as favorable in LatAm subjects as in nLAS, with an even greater reduction in hemorrhagic stroke seen in LatAm.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hospitalization; Humans; Intracranial Hemorrhages; Latin America; Male; Myocardial Infarction; Pyridines; Stroke; Thiazoles; Warfarin

The impact of different types of extracranial bleeding events on health-related quality of life and health-state utility among patients with atrial fibrillation is not well understood.. The ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol-5D (EQ-5D-3L) questionnaire, prospectively collected at 3-month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health-state utility over 12 months following the event. Longitudinal mixed-effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (-0.029 [-0.044 to -0.014;. All categories of bleeding events were associated with negative impacts on health-state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months.. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Embolism; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Health Status; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyridines; Quality of Life; Risk Factors; Stroke; Surveys and Questionnaires; Thiazoles; Time Factors; Treatment Outcome; Warfarin

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

Gastrointestinal (GI) bleeding in patients receiving anticoagulation agents can be caused by occult malignancies. We investigated the proportions and features of major GI bleeding (MGIB) events related to occult GI cancers in patients receiving anticoagulation therapy.. We analyzed data from the Randomized Evaluation of Long Term Anticoagulant Therapy study (conducted between December 2005 and March 2009 in 951 clinical centers in 44 countries worldwide), which compared the abilities of dabigatran vs warfarin to prevent stroke and systemic embolism in 18,113 patients with atrial fibrillation. Two blinded gastroenterologists independently reviewed source documents of MGIB events (n = 595) that occurred during the study period. We collected data on MGIB events caused by previously unidentified GI malignancies, and compared characteristics of MGIB events in patients who received dabigatran vs warfarin (primary end point), and in patients with bleeding from cancer, vs patients bleeding from a nonmalignant or unidentified source.. Of 546 unique MGIB events, 44 (8.1%) were found to be from GI cancers (34 of 398 MGIB events in dabigatran users and 10 of 148 MGIB events in warfarin users; P = .60). Colorectal cancer accounted for 35 of 44 of all cancers identified. There were more colorectal cancer-associated MGIB events in the dabigatran group (30 of 34) than in the warfarin group (5 of 10) (P = .02), but more gastric cancer-associated MGIB events in the warfarin group (5 of 10) than in the dabigatran group (1 of 34) (P = .001). There were no differences in the short-term outcomes of cancer-related MGIB events in the dabigatran vs the warfarin group, but 75% of all cancer-related MGIB events required at least 1 blood transfusion and the mean hospital stay was 10.1 days. Compared with MGIB events from a nonmalignant or unidentified source, MGIB from cancer occurred sooner (343.0 vs 223.1 d; P = .003), but the bleeding was more likely to be chronic (for >7 d) (27.3% vs 63.6%; P < .001).. In evaluating data from a study of the effects of anticoagulation therapy, we found approximately 1 of every 12 MGIB events to be related to an occult cancer. Approximately two thirds of cancer-related MGIB presents with chronic bleeding, and morbidity, and resource utilization is high.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chemoprevention; Dabigatran; Embolism; Female; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Male; Prevalence; Prospective Studies; Stroke; Warfarin

The use of non-vitamin K antagonist oral anticoagulants (NOACs) instead of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and coexisting valvular heart disease (VHD) is of substantial interest.. This study explored outcomes in patients with AF with and without VHD in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, comparing edoxaban with warfarin.. Valvular heart disease was defined as history or baseline echocardiography evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery (bioprosthesis replacement, valve repair, valvuloplasty). Patients with moderate to severe mitral stenosis or mechanical heart valves were excluded from the trial. Comparisons were made of rates of stroke/systemic embolic event (SSEE), major bleeding, additional efficacy and safety outcomes, as well as net clinical outcomes, in patients with or without VHD treated with edoxaban or warfarin, using adjusted Cox proportional hazards.. After adjustment for multiple baseline characteristics, compared with no-VHD patients (n = 18,222), VHD patients (n = 2,824) had a similar rate of SSEE but higher rates of death (hazard ratio [HR]: 1.40; 95% confidence interval [CI]:1.26 to 1.56; p <0.001), major adverse cardiovascular events (HR: 1.29; 95% CI: 1.16 to 1.43; p <0.001), and major bleeding (HR: 1.21; 95% CI: 1.03 to 1.42; p = 0.02). Higher-dose edoxaban regimen had efficacy similar to warfarin in the presence of VHD (for SSEE, HR: 0.69; 95% CI: 0.44 to 1.07, in patients with VHD, and HR: 0.91; 95% CI: 0.77 to 1.07, in patients without VHD; p interaction [p. The presence of VHD increased the risk of death, major adverse cardiovascular events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF. (Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs. Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391).

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Heart Valve Diseases; Hemorrhage; Humans; Male; Middle Aged; Pyridines; Stroke; Thiazoles; Warfarin

Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood.. We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors.. COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p=0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p<0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p=0.617).. COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

Obesity has been associated with increased cardiovascular risk in atrial fibrillation, but little is known in elderly patients with atrial fibrillation.. Post hoc analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial.. We studied 1588 elderly patients, who were categorized as normal body mass index (BMI, 18.5-25 kg/m(2); n=515 [32.4%]), overweight (BMI, 25-30 kg/m(2); n=711 [44.8%]), and obese (BMI≥30 kg/m(2); n=362 [22.8%]). There was a significant reduction in the composite outcome of cardiovascular death and stroke/systemic embolism with increasing BMI category, being 5.0%, 3.2%, and 1.5% per 100 patient-years, respectively (P for trend=0.01). Cox proportional hazards analysis found obesity to be associated with a lower risk of the primary composite outcome (hazard ratio, 0.29; 95% confidence interval, 0.11-0.77; P=0.01). In the warfarin arm (n=814), multivariate logistic regression analysis demonstrated that obesity was independently related to higher odds of time in therapeutic range ≥60% (odds ratio, 1.84; 95% confidence interval, 1.21-2.80; P=0.004).. Obesity was associated with a lower stroke and mortality rate in elderly anticoagulated atrial fibrillation patients. Obesity was related to good quality anticoagulation control.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Humans; Logistic Models; Male; Multivariate Analysis; Obesity; Oligosaccharides; Overweight; Proportional Hazards Models; Risk Factors; Stroke; Warfarin

Coagulation markers may improve monitoring the risk of stroke and bleeding in patients with atrial fibrillation (AF) during anticoagulant treatment. We examined baseline levels of D-dimer and their association with stroke, cardiovascular death and major bleeding in 6,202 AF patients randomised to dabigatran or warfarin in the RE-LY trial. The effects of treatment on serial levels of D-dimer and coagulation factor (F) VIIa in 2,567 patients were also analysed. Baseline D-dimer levels were related to the rate of stroke/systemic embolism (SEE) with 0.64 % in the lowest quartile (Q1, as reference) (D-dimer < 298 µg/l), 1.38 % Q2 (D-dimer 298-473 µg/l), 1.71 % Q3 (D-dimer 474-822 µg/l) and 2.00 % in Q4 (D-dimer > 822 µg/l) (p=0.0007). Similar associations were shown for cardiovascular death and major bleeding. Addition of baseline D-dimer to established clinical risk factors improved prediction of stroke/SEE, cardiovascular death and major bleeding (C-index increased from 0.66 to 0.68, 0.71 to 0.73 and 0.66 to 0.67, respectively). Dabigatran provided a greater reduction of D-dimer levels than warfarin regardless of baseline anticoagulant treatment. On-treatment levels of FVIIa were markedly reduced by warfarin (median 12.1-13.8 mU/ml) but significantly higher with dabigatran (median 39.4-49.0 mU/ml) at all-time points. Dabigatran is associated with greater reduction in D-dimer without the pronounced reduction of FVIIa seen with warfarin. These different effects on the coagulation system might explain the better efficacy and less intracranial bleeding observed with dabigatran compared with warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor VIIa; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Prognosis; Risk Factors; Stroke; Warfarin

In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia.. Patients aged ≥21 years with documented AF and CHADS score ≥2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0-3.0. Patients with a creatinine clearance of 30-50 ml/min, weighing ≤60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.34% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31-0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63-1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41-0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21-0.54, P<0.001).. Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population.

Topics: Aged; Aged, 80 and over; Asia, Eastern; Atrial Fibrillation; Double-Blind Method; Embolism; Hemorrhage; Humans; Pyridines; Stroke; Thiazoles; Warfarin

Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF-TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age.. Twenty-one thousand one-hundred and five patients enrolled in the ENGAGE AF-TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P<0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups (Ptrend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66-1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70-0.99]). The absolute risk difference in major bleeding (-82 events/10 000 pt-yrs) and in intracranial hemorrhage (-73 events/10 000 pt-yrs) both favored edoxaban over warfarin in older patients.. Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients.. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyridines; Stroke; Thiazoles; Treatment Outcome; Warfarin

Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin.. After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models.. Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban.. Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Topics: Aged; Atrial Fibrillation; Creatinine; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kidney; Male; Middle Aged; Proportional Hazards Models; Rivaroxaban; Stroke; Thrombophilia; Warfarin

In 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) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial.. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted.. TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported.. URL: ClinicalTrials.gov. Unique identifier: NCT00403767.

Topics: Aged; Anticoagulants; Asia; Atrial Fibrillation; Blood Coagulation; Drug Dosage Calculations; Drug Monitoring; Embolism; Europe; Female; Humans; International Normalized Ratio; Latin America; Male; North America; Predictive Value of Tests; South Africa; Stroke; Time Factors; Treatment Outcome; Warfarin

In Asian patients in RE-LY, dabigatran etexilate (DE) was as effective as warfarin, with a significantly lower bleeding risk. We evaluated the relationship between baseline renal function or CHADS2 score and efficacy or safety outcomes in these patients.. Asian patients (n=2,782) were categorized according to baseline renal function or CHADS2 score, and efficacy and safety outcomes were analyzed for DE (110 mg and 150 mg b.i.d.) vs. warfarin. There was an increase in the rates of stroke/systemic embolism and major bleeding with worsening renal function and CHADS2 score. For stroke/systemic embolism (primary efficacy endpoint), there was no treatment interaction for dabigatran at either 110 or 150 mg b.i.d. compared with warfarin related to patients' baseline renal function (Pinteraction=0.56 for DE 110 mg and 0.62 for DE 150 mg vs. warfarin) or CHADS2 score (Pinteraction=0.68 for DE 110 mg and 0.31 for DE 150 mg vs. warfarin). For major bleeding, there was no treatment interaction by creatinine clearance category observed for either dose (Pinteraction=0.60 and 0.62 for DE 110 mg and DE 150 mg, respectively). Baseline CHADS2 score had no significant effect on bleeding event rates with DE vs. warfarin.. Bleeding and stroke rates in Asian patients varied according to renal function and CHADS2 score, but the relative benefits of DE over warfarin were preserved when analyzed by subcategories.

Topics: Aged; Asian People; Creatinine; Dabigatran; Embolism; Female; Hemorrhage; Humans; Kidney; Male; Middle Aged; Stroke; Warfarin

Atrial fibrillation (AF) is a major risk factor for stroke and systemic embolism. Trials comparing warfarin with non-vitamin K oral anticoagulants (NOACs) have demonstrated that, when compared with warfarin, the NOACs are at least as effective in preventing stroke, although detailed analyses characterizing systemic embolic events (SEEs) are lacking.. We performed a prespecified analysis in 21,105 patients with AF enrolled in the ENGAGE AF-TIMI 48 trial, which compared 2 once-daily regimens of edoxaban with warfarin for the prevention of stroke and SEE. Of 1,016 patients who met the primary end point, 67 (6.6%) experienced an SEE of which 13% were fatal. Of 73 total SEEs (including recurrent events), 85% involved the extremities, and 41% required a surgical or percutaneous intervention. There were 23 (0.12%/year) SEEs with warfarin versus 15 with higher dose edoxaban (0.08%/year; hazard ratio vs warfarin 0.65; 95% CI 0.34-1.24; P = .19) and 29 with lower dose edoxaban (0.15%/year; hazard ratio vs warfarin 1.24; 95% CI 0.72-2.15; P = .43). In a meta-analysis of 4 warfarin-controlled phase 3 AF trials, NOACs significantly reduced the risk of SEE by 37% (relative risk 0.63; 95% CI 0.43-0.91; P = .01).. Although considerably less frequent than stroke, systemic embolism is associated with significant morbidity and mortality in patients with AF. Although the overall number of events was too small to show a significant difference in the risk of SEE between edoxaban and warfarin, a meta-analysis of all the NOAC trials demonstrates that NOACs significantly reduce the risk of SEE compared with warfarin.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Double-Blind Method; Embolism; Factor Xa; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Middle Aged; Myocardial Infarction; Pyridines; Retrospective Studies; Thiazoles; Thrombolytic Therapy; Treatment Outcome; Warfarin

In 21,105 patients with atrial fibrillation (AF), the ENGAGE AF-TIMI 48 trial demonstrated that both higher dose (60mg/30mg dose reduced) and lower dose (30mg/15mg dose reduced) once-daily regimens of edoxaban were non-inferior to warfarin for the prevention of stroke or systemic embolism (SE), with significantly lower rates of bleeding and cardiovascular death. Higher dose edoxaban was associated with a greater reduction in the risk of ischemic stroke than lower dose edoxaban, and the FDA approved higher dose edoxaban in patients with creatinine clearance ≤95mL/min. This study evaluated the economic value of higher dose edoxaban vs warfarin based on data from patients in ENGAGE within the FDA-approved population.. We assessed the cost-effectiveness of edoxaban vs warfarin over a lifetime horizon from the US healthcare system perspective using a Markov model based on a combination of ENGAGE AF-TIMI 48 trial data, US life tables, and published literature on the costs and long-term outcomes of non-fatal cardiovascular and bleeding events. Data from the ENGAGE AF-TIMI 48 trial were used to calculate age-adjusted event rates for warfarin and hazard ratios (HRs) for the relative impact of edoxaban on embolic and bleeding complications. Based on the wholesale acquisition price, edoxaban and warfarin were assumed to cost $9.24 and $0.36/day, respectively.. For edoxaban vs warfarin, lifetime incremental costs and QALYs were $16,384 and 0.444, respectively, yielding an incremental cost-effectiveness ratio (ICER) of $36,862/QALY gained, using data from patients with creatinine clearance ≤95mL/min in ENGAGE AF-TIMI 48. ICERs were more favorable for patients without compared to those with prior warfarin use; ICERs differed minimally by CHADS2 score.. Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SE in patients with atrial fibrillation and creatinine clearance ≤95mL/min. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of-life impact of stroke and bleeding events, and were favorable across both CHADS2 score stroke-risk categories.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Monitoring; Embolism; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Selection; Pyridines; Risk Assessment; Stroke; Survival Analysis; Thiazoles; Treatment Outcome; Warfarin

This study assessed the effects and safety of rivaroxaban versus warfarin in Chinese patients with atrial fibrillation. In this double-blind clinical trial, a total of 353 consecutive patients with atrial fibrillation who were at risk of stroke or systemic embolism were enrolled to receive either rivaroxaban or warfarin. The primary effect endpoint occurred in five patients in the rivaroxaban group (2.29% per year) and in seven patients in the warfarin group (2.91% per year) (hazard ratio with warfarin, 0.76, 95% CI, 0.64-0.91; p = 0.03). Major and non-major clinically relevant bleeding occurred in 38 patients (14.3% per year) in the rivaroxaban group and in 36 patients (13.7% per year) in the warfarin group (hazard ratio rivaroxaban versus warfarin, 1.07; 95% CI, 0.93-1.14; p = 0.39). Adverse events were similar between these two arms (p > 0.05). In conclusion, oral administration of rivaroxaban reduced the risk of stroke or systemic embolism without significantly increasing the safety concern.

Topics: Administration, Oral; Aged; Anticoagulants; Asian People; Atrial Fibrillation; China; Double-Blind Method; Embolism; Female; Hemorrhage; Humans; Male; Morpholines; Primary Prevention; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Time Factors; Treatment Outcome; Warfarin

We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients.. In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10).. Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Double-Blind Method; Embolism; Female; Humans; Kaplan-Meier Estimate; Male; Morpholines; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Rivaroxaban; Stroke; Thiophenes; Ticlopidine; Treatment Outcome; Warfarin

We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF).. In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91%, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10% vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78%, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease.. Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Double-Blind Method; Drug Therapy, Combination; Embolism; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Stroke; Treatment Outcome; Warfarin

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm.. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037).. Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Humans; Male; Morpholines; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

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

Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function.. Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to <80, and <50 mL/min was estimated in 32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism, major bleeding, and all-cause mortality increased as renal function decreased. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction P>0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively (P<0.05). The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate ≥80 mL/min.. The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate ≥80 mL/min.. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Dose-Response Relationship, Drug; Embolism; Female; Glomerular Filtration Rate; Humans; Internationality; Kidney; Male; Middle Aged; Models, Biological; Risk Factors; Stroke; Treatment Outcome; Warfarin

The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age.. A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes.. The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Drug Administration Schedule; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pyrazoles; Pyridones; Risk Factors; Stroke; Treatment Outcome; Warfarin; Young Adult

Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear.. This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta>4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization.. The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups.. Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating.. http://www.clinicaltrials.gov. Unique identifier: NCT00235248.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aorta, Thoracic; Aortic Diseases; Aspirin; Brain Ischemia; Clopidogrel; Drug Therapy, Combination; Embolism; Female; Humans; Male; Middle Aged; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Prospective Studies; Single-Blind Method; Stroke; Ticlopidine; Treatment Outcome; 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

Time in therapeutic range (TTR) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (cTTR) since such analysis preserves randomized comparisons.. TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio (INR) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INRs were performed via standardized finger-stick point-of-care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non-central nervous system embolism) was examined by quartiles of cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower-risk patients as reflected by lower CHADS2 scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of cTTRs (P value for interaction=0.71). The hazard of major and non-major clinically relevant bleeding increased with cTTR (P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold cTTR values.. The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Double-Blind Method; Drug Monitoring; Embolism; Europe; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Morpholines; North America; Point-of-Care Systems; Predictive Value of Tests; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Time Factors; Treatment Outcome; 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

Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted preprocedure, whether bridging therapy was used, and the proportion of patients who experienced important clinical outcomes during the 30 days postprocedure. Of 10 674 procedures performed during follow-up in 5924 patients, 9260 were included in this analysis. Anticoagulant treatment was not interrupted preprocedure 37.5% of the time. During the 30 days postprocedure, stroke or systemic embolism occurred after 16/4624 (0.35%) procedures among apixaban-treated patients and 26/4530 (0.57%) procedures among warfarin-treated patients (odds ratio [OR] 0.601; 95% confidence interval [CI] 0.322-1.120). Major bleeding occurred in 74/4560 (1.62%) procedures in the apixaban arm and 86/4454 (1.93%) in the warfarin arm (OR 0.846; 95% CI 0.614-1.166). The risk of death was similar with apixaban (54/4624 [1.17%]) and warfarin (49/4530 [1.08%]) (OR 1.082; 95% CI 0.733-1.598). Among patients in ARISTOTLE, the 30-day postprocedure stroke, death, and major bleeding rates were low and similar in apixaban- and warfarin-treated patients, regardless of whether anticoagulation was stopped beforehand. Our findings suggest that many patients on chronic anticoagulation can safely undergo procedures; some will not require a preprocedure interruption of anticoagulation. ARISTOTLE was registered at www.clinicaltrials.gov as #NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Postoperative Complications; Pyrazoles; Pyridones; Stroke; Treatment Outcome; Warfarin

While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions.. To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin.. PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2 score ≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5% and superiority a probability of 95% or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups.. Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3).. A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat.. At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95% credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, >99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95% CI, 0.21-0.75; P = .005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95% CI, 0.45-0.98; P = .04).. After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.. clinicaltrials.gov Identifier: NCT00129545.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Bayes Theorem; Cardiac Catheterization; Cardiovascular Diseases; Embolism; Female; Humans; Male; Middle Aged; Prosthesis Implantation; Risk Factors; Stroke; Survival Analysis; Treatment Outcome; Warfarin

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984).

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Embolism; Female; Fibrinolytic Agents; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Assessment; Stroke; Warfarin

It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF).. A total of 18 201 patients with AF [2786 (15.3%) with paroxysmal and 15 412 (84.7%) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction = 0.71), all-cause mortality (P for interaction = 0.75), and major bleeding (P for interaction = 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions >0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98%; P = 0.003, adjusted P = 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81%; P = 0.0002, adjusted P = 0.066).. The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Cause of Death; Electric Countershock; Electrocardiography; Embolism; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Stroke; Treatment Outcome; Warfarin

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

A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD.. In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD.. In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Embolism; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Factors; Stroke; Treatment Outcome; Warfarin

Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known.. We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding.. The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32).. Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Double-Blind Method; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pyridines; Stroke; Thiazoles; Warfarin

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

The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial showed that dabigatran etexilate 150 mg BID was superior and dabigatran etexilate 110 mg BID was noninferior to warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation. In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and did not receive concomitant antiplatelets.. All comparisons used a Cox proportional hazards model with adjustments made for risk factors for bleeding. A time-dependent analysis was performed when comparing patients with concomitant antiplatelets with those without. Of 18 113 patients, 6952 (38.4%) received concomitant aspirin or clopidogrel at some time during the study. Dabigatran etexilate 110 mg BID was noninferior to warfarin in reducing stroke and systemic embolism, whether patients received antiplatelets (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.70-1.25) or not (HR, 0.87; 95% CI, 0.66-1.15; interaction P=0.738). There were fewer major bleeds than warfarin in both subgroups (HR, 0.82; 95% CI, 0.67-1.00 for patients who used antiplatelets; HR, 0.79; 95% CI, 0.64-0.96 for patients who did not; interaction P=0.794). Dabigatran etexilate 150 mg BID reduced the primary outcome of stroke and systemic embolism in comparison with warfarin. This effect seemed attenuated among patients who used antiplatelets (HR, 0.80; 95% CI, 0.59-1.08) in comparison with those who did not (HR, 0.52; 95% CI, 0.38-0.72; P for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR, 0.93; 95% CI, 0.76-1.12 for patients who used antiplatelets; HR, 0.94; 95% CI, 0.78-1.15 for patients who did not; P for interaction=0.875). In the time-dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR, 1.60; 95% CI, 1.42-1.82). Dual antiplatelet seemed to increased this even more (HR, 2.31; 95% CI, 1.79-2.98). The absolute risks were lowest on dabigatran etexilate 110 mg BID in comparison with dabigatran etexilate 150 mg BID or warfarin.. Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between dabigatran etexilate 110 mg BID and dabigatran etexilate 150 mg BID requires a careful assessment of characteristics that influence the balance between benefit and harm.. URL: http://clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Drug Therapy, Combination; Embolism; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyridines; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

The multicenter PROTECT AF study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) was conducted to determine whether percutaneous left atrial appendage closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation.. Patients (n=707) with nonvalvular atrial fibrillation and at least 1 risk factor (age >75 years, hypertension, heart failure, diabetes, or prior stroke/transient ischemic attack) were randomized to either the Watchman device (n=463) or continued warfarin (n=244) in a 2:1 ratio. After device implantation, warfarin was continued for ≈45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups, respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy end point included stroke, systemic embolism, and cardiovascular death, and the primary analysis was by intention to treat. After 1588 patient-years of follow-up (mean 2.3±1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100 patient-years) in the Watchman and warfarin groups, respectively (relative risk, 0.71; 95% confidence interval, 0.44%-1.30% per year), which met the criteria for noninferiority (probability of noninferiority >0.999). There were more primary safety events in the Watchman group (5.5% per year; 95% confidence interval, 4.2%-7.1% per year) than in the control group (3.6% per year; 95% confidence interval, 2.2%-5.3% per year; relative risk, 1.53; 95% confidence interval, 0.95-2.70).. The "local" strategy of left atrial appendage closure is noninferior to "systemic" anticoagulation with warfarin. PROTECT AF has, for the first time, implicated the left atrial appendage in the pathogenesis of stroke in atrial fibrillation.. : URL: http://www.clinicaltrials.gov. Unique identifier: NCT00129545.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Appendage; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Embolism; Female; Follow-Up Studies; Humans; Male; Prostheses and Implants; Stroke; Ticlopidine; Treatment Outcome; Warfarin

The purpose of this study was to investigate the frequency and clinical impact of incomplete left atrial appendage (LAA) sealing and consequent peri-device residual blood flow in patients undergoing percutaneous LAA closure with the Watchman device (Atritech, Inc., Plymouth, Minnesota).. During percutaneous LAA closure for stroke prophylaxis, the geometric variability of the LAA ostium may result in an incomplete seal of the LAA. On the one hand, this could enhance thrombus formation and embolization of thrombi around the device into the circulation; on the other hand, the relatively small size of these leaks may preclude clinically relevant embolizations.. Patients randomly assigned to device implantation in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial were analyzed. Transesophageal echocardiography was performed at 45 days, 6 months, and 12 months. Per the study protocol, patients discontinued warfarin therapy if the 45-day Transesophageal echocardiogram revealed either minimal or no peri-device flow (jet ≤5 mm width). The impact of peri-device flow severity, defined as minor, moderate, or major (<1 mm, 1 mm to 3 mm, >3 mm, respectively) on the composite primary efficacy endpoint (stroke, systemic embolism, and cardiovascular death) is expressed as hazard ratio (HR) with 95% confidence interval (CI).. Transesophageal echocardiography follow-up revealed that 32.0% of implanted patients had at least some degree of peri-device flow at 12 months. The HR of the primary efficacy endpoint per 1 mm larger per-device flow was 0.84 (95% CI: 0.62 to 1.14; p = 0.256). Compared to patients with no peri-device flow, the HRs were 0.85 (95% CI: 0.11 to 6.40), 0.83 (95% CI: 0.33 to 2.09), and 0.48 (95% CI: 0.11 to 2.09) for minor, moderate, and major peri-device flow, respectively (p = 0.798). Compared to patients with no peri-device flow who discontinued warfarin, the HR for patients with any peri-device flow and continuing warfarin was 0.63 (95% CI: 0.14 to 2.71; p = 0.530).. These data indicate that residual peri-device flow into the LAA after percutaneous closure with the Watchman device was common, and is not associated with an increased risk of thromboembolism. This finding should be interpreted with caution as the low event rate decreases the confidence of this conclusion.

Topics: Aged; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Electrocardiography; Embolism; Female; Follow-Up Studies; Humans; Incidence; Male; Prospective Studies; Prostheses and Implants; Prosthesis Design; Risk Factors; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States (1). Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 (2). Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke (3). The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF (3). Rate control is achieved by administration of pharmacological agents, such as β-blockers, that lower the heart rate until it reaches a less symptomatic state (3). Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods (4-6). In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects (3), or even increases in mortality in patients with structural heart defects (7). Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue (8), but don't reliably prevent thromboembolic events (6). Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism (9,10). However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding (2). As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke (10). Other alternatives to warfarin, such as dabigatran (11) or rivaroxaban (12) demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminati

Topics: Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Cardiac Surgical Procedures; Embolism; Humans; Prostheses and Implants; Warfarin

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF.. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050).. J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Morpholines; Prospective Studies; Rivaroxaban; Stroke; Thiophenes; Warfarin

The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin.. RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (R(2)=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65-6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85-1.00).. Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Female; Humans; International Normalized Ratio; Internationality; Male; Proportional Hazards Models; Regression Analysis; Risk Factors; Stroke; Treatment Outcome; Warfarin

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding.. ARISTOTLE was a double-blind, randomised trial that enrolled 18,201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2·0-3·0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984.. Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or ≥3, p for interaction=0·4457; or CHA(2)DS(2)VASc 1, 2, or ≥3, p for interaction=0·1210) or bleeding (HAS-BLED 0-1, 2, or ≥3, p for interaction=0·9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0·4018; CHA(2)DS(2)VASc, p for interaction=0·2059; HAS-BLED, p for interaction=0·7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0·22, 95% CI 0·10-0·48) than in those with HAS-BLED scores of 0-1 (HR 0·66, 0·39-1·12; p for interaction=0·0604).. Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events.. Bristol-Myers Squibb and Pfizer.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Risk Assessment; Stroke; Treatment Outcome; Warfarin

The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) randomized trial compared left atrial appendage closure against warfarin in atrial fibrillation (AF) patients with CHADS₂ ≥1. Although the study met the primary efficacy end point of being noninferior to warfarin therapy for the prevention of stroke/systemic embolism/cardiovascular death, there was a significantly higher risk of complications, predominantly pericardial effusion and procedural stroke related to air embolism. Here, we report the influence of experience on the safety of percutaneous left atrial appendage closure.. The study cohort for this analysis included patients in the PROTECT AF trial who underwent attempted device left atrial appendage closure (n=542 patients) and those from a subsequent nonrandomized registry of patients undergoing Watchman implantation (Continued Access Protocol [CAP] Registry; n=460 patients). The safety end point included bleeding- and procedure-related events (pericardial effusion, stroke, device embolization). There was a significant decline in the rate of procedure- or device-related safety events within 7 days of the procedure across the 2 studies, with 7.7% and 3.7% of patients, respectively, experiencing events (P=0.007), and between the first and second halves of PROTECT AF and CAP, with 10.0%, 5.5%, and 3.7% of patients, respectively, experiencing events (P=0.006). The rate of serious pericardial effusion within 7 days of implantation, which had made up >50% of the safety events in PROTECT AF, was lower in the CAP Registry (5.0% versus 2.2%, respectively; P=0.019). There was a similar experience-related improvement in procedure-related stroke (0.9% versus 0%, respectively; P=0.039). Finally, the functional impact of these safety events, as defined by significant disability or death, was statistically superior in the Watchman group compared with the warfarin group in PROTECT AF. This remained true whether significance was defined as a change in the modified Rankin score of ≥1, ≥2, or ≥3 (1.8 versus 4.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.24 to 0.82; 1.5 versus 3.7 events per 100 patient-years; relative risk, 0.41; 95% confidence interval, 0.22 to 0.82; and 1.4 versus 3.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.22 to 0.88, respectively).. As with all interventional procedures, there is a significant improvement in the safety of Watchman left atrial appendage closure with increased operator experience. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00129545.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Cardiac Catheterization; Echocardiography, Transesophageal; Embolism; Female; Humans; Male; Middle Aged; Pericardial Effusion; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; 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

The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism.. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Hemorrhage; Humans; Intention to Treat Analysis; Male; Middle Aged; Morpholines; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages.. We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [15 mg/day if creatinine clearance (CrCl) 30-49 mL/min] or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Compared with patients with CrCl >50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.57-1.23] in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P = 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P = 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years; P = 0.047) occurred less often with rivaroxaban.. Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function. There was no evidence of heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Hemorrhage; Humans; Male; Morpholines; Renal Insufficiency; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

AZD0837 is an investigational oral anticoagulant which is converted to the active form, AR-H067637, a selective direct thrombin inhibitor. The present study, a multicentre, randomised, parallel-group, dose-guiding study, assessed the safety and tolerability of an immediate-release formulation of AZD0837 compared with dose-adjusted warfarin in the prevention of stroke and systemic embolic events in atrial fibrillation (AF) patients. Two hundred fifty AF patients with at least one additional risk factor for stroke were randomised to receive either immediate-release AZD0837 (150mg twice daily [bid] or 350mg bid, blinded treatment) or dose-adjusted warfarin (international normalised ratio 2.0-3.0, open treatment) for three months. The safety and tolerability of 150mg bid AZD0837 appeared to be as good as that of warfarin. Total bleeding events were six with 150mg bid AZD0837, 15 with 350mg bid AZD0837 and eight with warfarin. Alanine aminotransferase elevations (>3xupper limit of normal) were infrequent, without apparent differences between treatment groups. A numerically higher incidence of serious adverse events was observed with 350mg bid AZD0837 compared with 150mg bid, with six of 13 being cardiac related, all with different diagnoses. An increase in mean serum creatinine of approximately 10% was observed in both AZD0837 groups, which returned to baseline after completion of therapy. There were no strokes, transient ischaemic attacks or cerebral haemorrhages with any of the treatments. In conclusion, the safety and tolerability of 150mg bid immediate-release AZD0837 appeared to be as good as that of dose-adjusted warfarin. However, larger studies will be needed to define the safety profile of AZD0837.

Topics: Amidines; Anticoagulants; Atrial Fibrillation; Azetidines; Dose-Response Relationship, Drug; Embolism; Hemorrhage; Humans; Serine Proteinase Inhibitors; Stroke; Thrombin; Treatment Outcome; Warfarin

In the current era of early revascularization and routine use of dual antiplatelet therapy, the incremental benefit of warfarin to reduce the incidence of left ventricular thrombus (LVT) in patients with impaired left ventricular ejection fraction post anterior ST-elevation myocardial infarction (aSTEMI), remains uncertain. The purpose of this study is to assess the feasibility of evaluating the added benefit and safety of triple therapy (TT-warfarin, ASA, and clopidogrel) versus dual therapy (DT-ASA and clopidogrel) in patients at risk of LVT post aSTEMI.. Open-label randomized controlled trial.. aSTEMI, ejection fraction <40%, and no evidence of LVT. EXCLUSION: contraindication to, or alternate indication for anticoagulation.. TT versus DT.. pre-discharge and 3 month echocardiogram.. composite of death, MI, stroke, systemic embolizarion, LVT or major bleeding at three months. 295 patients with aSTEMI were screened: 27% of patients with LVEF < 40% had an LVT; 20/52 eligible patients were randomized to receive TT (n = 10) or DT (n = 10). Baseline characteristics: mean age 60 years, male gender 65%, diabetics 20%, and in hospital PCI 95%. There was no significant difference in the composite endpoint at 3 months (TT-20% with 1 LVT and 1 major bleed versus DT-10% with 1 MI). The incidence of definite or probable LVT in the screened population of patients post aSTEMI with an LVEF < 40% was 26.6% despite 94% having early revascularization. STEMI patients have a high incidence of LVT despite the routine use of early revascularization and dual antiplatelet therapy. More effective antithrombotic strategies merit evaluation in adequately powered randomized trials.

Topics: Aged; Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Embolism; Feasibility Studies; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Ontario; Platelet Aggregation Inhibitors; Recurrence; Stroke; Thrombosis; Ticlopidine; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; 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

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

There are limited data on the causes and severity of subsequent stroke in patients presenting initially with TIA or stroke attributed to intracranial arterial stenosis.. We evaluated the location, type (lacunar vs nonlacunar), cause, and severity of stroke in patients who had an ischemic stroke endpoint in the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial.. Of the 569 patients enrolled in the WASID trial, 106 patients (18.6%) had an ischemic stroke during a mean follow-up of 1.8 years. Stroke occurred in the territory of the symptomatic artery in 77 (73%) of 106 patients. Among the 77 strokes in the territory, 70 (91%) were nonlacunar and 34 (44%) were disabling. Stroke out of the territory of the symptomatic artery occurred in 29 (27%) of 106 patients. Among these 29 strokes, 24 (83%) were nonlacunar, 14 (48%) were attributed to previously asymptomatic intracranial stenosis, and 9 (31%) were disabling.. Most subsequent strokes in patients with symptomatic intracranial artery stenosis are in the same territory and nonlacunar, and nearly half of the strokes in the territory are disabling. The most commonly identified cause of stroke out of the territory was a previously asymptomatic intracranial stenosis. Penetrating artery disease was responsible for a low number of strokes.

Topics: Anticoagulants; Aspirin; Atherosclerosis; Brain Ischemia; Cerebral Arteries; Cerebrovascular Disorders; Constriction, Pathologic; Double-Blind Method; Embolism; Endpoint Determination; Humans; Platelet Aggregation Inhibitors; Recurrence; Stents; Stroke; Warfarin

In patients with non-valvular atrial fibrillation, embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. We assessed the efficacy and safety of percutaneous closure of the LAA for prevention of stroke compared with warfarin treatment in patients with atrial fibrillation.. Adult patients with non-valvular atrial fibrillation were eligible for inclusion in this multicentre, randomised non-inferiority trial if they had at least one of the following: previous stroke or transient ischaemic attack, congestive heart failure, diabetes, hypertension, or were 75 years or older. 707 eligible patients were randomly assigned in a 2:1 ratio by computer-generated randomisation sequence to percutaneous closure of the LAA and subsequent discontinuation of warfarin (intervention; n=463) or to warfarin treatment with a target international normalised ratio between 2.0 and 3.0 (control; n=244). Efficacy was assessed by a primary composite endpoint of stroke, cardiovascular death, and systemic embolism. We selected a one-sided probability criterion of non-inferiority for the intervention of at least 97.5%, by use of a two-fold non-inferiority margin. Serious adverse events that constituted the primary endpoint for safety included major bleeding, pericardial effusion, and device embolisation. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00129545.. At 1065 patient-years of follow-up, the primary efficacy event rate was 3.0 per 100 patient-years (95% credible interval [CrI] 1.9-4.5) in the intervention group and 4.9 per 100 patient-years (2.8-7.1) in the control group (rate ratio [RR] 0.62, 95% CrI 0.35-1.25). The probability of non-inferiority of the intervention was more than 99.9%. Primary safety events were more frequent in the intervention group than in the control group (7.4 per 100 patient-years, 95% CrI 5.5-9.7, vs 4.4 per 100 patient-years, 95% CrI 2.5-6.7; RR 1.69, 1.01-3.19).. The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than in the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.. Atritech.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Embolism; Europe; Female; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pericardial Effusion; Proportional Hazards Models; Prostheses and Implants; Prosthesis Design; Risk Factors; Safety; Stroke; Treatment Outcome; United States; Warfarin

Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.. In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism.. Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051).. In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Chi-Square Distribution; Dabigatran; Double-Blind Method; Dyspepsia; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Liver; Male; Middle Aged; Myocardial Infarction; Prodrugs; Proportional Hazards Models; Pyridines; Stroke; Warfarin

Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE) may be related to INR control.. We analyzed the relationship between INR control and the rates of death, bleeding, MI, and stroke or SEE among 3587 patients with atrial fibrillation randomized to receive warfarin treatment in the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation) III and V trials. The mean+/-SD follow-up was 16.6 +/- 6.3 months. Patients were divided into 3 equal groups (those with good control [>75%], those with moderate control [60%-75%], or those with poor control [<60%]) according to the percentage time with an INR of 2.0 to 3.0. Outcomes were compared according to INR control. The main outcome measures were death, bleeding, MI, and stroke or SEE.. The poor control group had higher rates of annual mortality (4.20%) and major bleeding (3.85%) compared with the moderate control group (1.84% and 1.96%, respectively) and the good control group (1.69% and 1.58%, respectively) (P<.01 for all). Compared with the good control group, the poor control group had higher rates of MI (1.38% vs 0.62%, P = .04) and of stroke or SEE (2.10% vs 1.07%, P = .02).. In patients with atrial fibrillation taking warfarin, the risks of death, MI, major bleeding, and stroke or SEE are related to INR control. Good INR control is important to improve patient outcomes.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Myocardial Infarction; Stroke; Survival Rate; Treatment Outcome; Warfarin

Warfarin prevents stroke in atrial fibrillation (AF); however, concerns regarding international normalized ratio control and hemorrhage limit its use in the elderly. The oral direct thrombin inhibitors (DTIs) are potential alternatives to warfarin, offering fixed dosing without drug and dietary interactions and the need for international normalized ratio monitoring. Although ximelagatran, a DTI studied in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation trials, has been withdrawn, development of other DTIs continues. We report our experience in elderly high-risk AF patients on ximelagatran compared with warfarin therapy.. Data from patients with AF and stroke risk factors randomized in Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials to ximelagatran or warfarin were analyzed for stroke/systemic emboli, bleeding, and raised alanine aminotransferase levels in those >or=75 (n=2804) and <75 (n=4525) years.. Ximelagatran was as effective as warfarin in reducing stroke/systemic emboli in the elderly (2.23%/y with ximelagatran vs 2.27%/y with warfarin) as in younger patients (1.25%/y vs 1.28%/y). Total bleeds were significantly lower with ximelagatran compared with warfarin in elderly (40% vs 45%, P=0.01) and younger (27% vs 35%, P<0.001) patients. Raised alanine aminotransferase values (>3-fold elevation) among ximelagatran patients were more common in older (7.5% old vs 5.3% young) patients, particularly women (9.5% elderly women vs 6.1% elderly men).. In high-risk elderly AF patients, ximelagatran is as effective as warfarin with less bleeding, but alanine aminotransferase elevations are common, particularly in elderly women. Oral DTIs for stroke prevention show promise in elderly patients.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Alanine Transaminase; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Cerebral Hemorrhage; Double-Blind Method; Embolism; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Sex Characteristics; Sex Factors; Stroke; Thrombin; Treatment Outcome; Up-Regulation; Warfarin

The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors. Methods and results The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions < or =35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization.. Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction.

Topics: Adult; Aged; Anticoagulants; Aspirin; Clopidogrel; Embolism; Female; Heart Failure; Humans; Male; Middle Aged; Patient Selection; Platelet Aggregation Inhibitors; Prospective Studies; Research Design; Ticlopidine; Warfarin

Topics: Adolescent; Ambulatory Care; Ambulatory Care Facilities; Anticoagulants; Australia; Child; Child, Preschool; Clinical Trials as Topic; Embolism; Hemorrhage; Humans; Incidence; Infant; Outcome Assessment, Health Care; Pediatrics; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Warfarin

Secondary prevention studies for cardioembolic strokes show a remarkable variability in stroke recurrence rates. Various reports have raised questions regarding differences in baseline clinical characteristics and in methodology to explain this wide variability.. The purpose of the present study is to examine the 2-year outcome after first cardioembolic stroke of atrial origin and to correlate secondary prognosis with left atrial and left atrial appendage dysfunction.. Baseline evaluation included computed tomographic and/or magnetic resonance scanning, Doppler scanning, digital subtraction angiography, and transthoracic and transesophageal echocardiography to establish the diagnosis of atrial source of emboli. Twenty-six patients in nonrheumatic atrial fibrillation and 13 in sinus rhythm were followed for recurrent stroke and vascular death as endpoints (event +/-).. Patients in sinus rhythm had a total of 23% (standard deviation +/- 12%) recurrence rate. All event (+) patients were on aspirin and died from this second cardioembolic stroke. Of patients in nonrheumatic atrial fibrillation, 50% were event (+) at the end of the first year (death rate 46%). Patients on warfarin therapy had 20% recurrence rate versus 70% on aspirin (relative risk 0, 18, 95% confidence interval, 0.05-0.48, p 0.041). Inward peak velocity of left atrial appendage was the only echocardiographic variable significantly reduced in event (+) patients (21 +/- 7 vs. 31 +/- 17 cm/s, p 0.048).. Patients with nonrheumatic atrial fibrillation and first atrial origin cardioembolic stroke are at increased risk for recurrence if severe dysfunction of the left atrial appendage is present and if they do not receive warfarin treatment. Patients with sinus rhythm and first atrial origin cardioembolic stroke form a small stroke subgroup, in which recurrences are accompanied by a remarkably high death rate.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Echocardiography, Transesophageal; Embolism; Female; Follow-Up Studies; Humans; Male; Prognosis; Secondary Prevention; Sex Factors; Stroke; Survival Analysis; Warfarin

The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy.. In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death.. There was no significant difference between the two treatment groups in the rate of embolic events (five embolic events among 619 patients in the transesophageal-echocardiography group [0.8 percent]) vs. three among 603 patients in the conventional-treatment group [0.5 percent], P=0.50). However, the rate of hemorrhagic events was significantly lower in the transesophageal-echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent], P=0.03). Patients in the transesophageal-echocardiography group also had a shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days, P<0.001) and a greater rate of successful restoration of sinus rhythm (440 patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status.. The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Echocardiography, Transesophageal; Electric Countershock; Embolism; Female; Heart Atria; Heart Diseases; Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Prospective Studies; Stroke; Thromboembolism; Thrombosis; Warfarin

We compared the efficacy of very-low-intensity oral anticoagulation (OA) with that of the recommended standard low-intensity oral anticoagulation, using international normalized ratios (INRs). We enrolled 101 patients into a pilot study--51 patients in the very-low-intensity anticoagulation arm (INR 1.4 to 2.0) and 50 in the standard low-intensity anticoagulation arm (INR 2.0 to 3.0). They were monitored for thrombotic/embolic and hemorrhagic complications for an average follow-up of 1.5 years. Two thrombotic/embolic events occurred in the very-low-intensity group; no thrombotic/embolic events occurred in the standard low-intensity group. No major bleeding occurred in the very-low-intensity group; one major hemorrhagic event occurred in the standard low-intensity group. These findings did not achieve a statistically significant difference in major complications between the two groups. It appears that very-low-intensity OA (INR 1.4 to 2.0) is as effective in preventing thromboses as standard low-intensity OA (INR 2.0 to 3.0).

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Drug Monitoring; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Patient Compliance; Pilot Projects; Pulmonary Embolism; Recurrence; Thrombophlebitis; Thrombosis; Warfarin

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Embolism; Female; Follow-Up Studies; Humans; Isoindoles; Italy; Male; Middle Aged; Phenylbutyrates; Platelet Aggregation Inhibitors; Risk Factors; Time Factors; Warfarin

The hemostatic condition under low-intensity anticoagulation in cardiac disorders is not fully elucidated. The aim of this study was to ascertain whether hemostatic molecular markers are a useful assessment for anticoagulation to detect the hypercoagulable state. A hematologic study was performed in 75 outpatients, without thromboembolic episodes, treated with low-intensity anticoagulation (average international normalized ratio [INR] 1.72) because of potential cardiac sources of arterial emboli, and in 40 age-matched control subjects. The average level of thrombin-antithrombin III complex (TAT) was significantly lower in patients than in control subjects (p = 0.005), and the mean value of D-dimer was not statistically different between patients and control subjects. Although TAT correlated moderately with D-dimer (r = 0.45, p = 0.0001), INR did not correlate with TAT or D-dimer. Elevated TAT > 3.0 ng/ml and/or D-dimer S 150 ng/ml were observed in 15 patients (20.0%), whereas the remaining 60 patients (80.0%) had no obvious increase in the level of TAT or D-dimer at overall INR. Antithrombin III activity did not correlate significantly with INR, but protein C activity and free protein S antigen showed a significant negative relation to INR (r = 0.82, r = 0.62, respectively, p = 0.0001). Low-intensity anticoagulation was sufficient to reduce coagulation and subsequent fibrinolytic activation in cardiac disorders, but may not be sufficient in some patients with elevated TAT or D-dimer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Tests; Embolism; Female; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Male; Middle Aged; Peptide Hydrolases; Warfarin

Despite the use of warfarin, major systemic embolism remains an important complication in patients with heart-valve replacement. Although the addition of antiplatelet agents has the potential to reduce this complication, their efficacy and safety when given in combination with warfarin are uncertain.. In a randomized, double-blind, placebo-controlled trial, we assessed the efficacy and safety of adding aspirin (100 mg per day) to warfarin treatment (target international normalized ratio, 3.0 to 4.5) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism.. A total of 186 patients were randomly assigned to aspirin and 184 to placebo, and they were followed for up to 4 years (average, 2.5). Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients (1.9 percent per year) and 24 placebo-treated patients (8.5 percent per year) (risk reduction with aspirin, 77 percent; 95 percent confidence interval, 44 to 91 percent; P < 0.001). Major systemic embolism, nonfatal intracranial hemorrhage, or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin (3.9 percent per year) and 28 patients assigned to placebo (9.9 percent per year) (risk reduction, 61 per cent; 95 percent confidence interval, 24 to 80 percent; P = 0.005); major systemic embolism or death from any cause occurred in 13 patients (4.2 percent) and 33 patients (11.7 percent), respectively (risk reduction, 65 percent; 95 percent confidence interval, 33 to 82 percent; P < 0.001); and death from all causes occurred in 9 patients (2.8 percent) and 22 patients (7.4 percent), respectively (risk reduction, 63 percent; 95 percent confidence interval, 19 to 83 percent; P = 0.01). Bleeding occurred in 71 patients in the aspirin group (35.0 percent), as compared with 49 patients in the placebo group (22.0 percent) (increase in risk, 55 percent; 95 percent confidence interval, 8 to 124 percent; P = 0.02); major bleeding occurred in 24 and 19 patients, respectively (increase in risk, 27 percent; 95 percent confidence interval, -30 to 132 percent; P = 0.43).. In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves, the addition of aspirin to warfarin therapy reduced mortality, particularly mortality from vascular causes, together with major systemic embolism. Although there was some increase in bleeding, the risk of the combined treatment was more than offset by the considerable benefit.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Confidence Intervals; Double-Blind Method; Drug Therapy, Combination; Embolism; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Likelihood Functions; Male; Middle Aged; Prosthesis Design; Warfarin

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Therapy, Combination; Embolism; Humans; Meta-Analysis as Topic; Research Design; Warfarin

Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.. The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.. Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Warfarin

After tissue heart valve replacement 108 patients were randomised to standard anticoagulant control with rabbit brain thromboplastin (Dade C reagent, therapeutic range 18-24 s; international normalised ratio 2.5-40) and 102 to a less intensive regimen controlled with human brain thromboplastin (Manchester Comparative Reagent, therapeutic range 26-30 s; INR 2.0-2.25). Treatment was continued for three months, outcome measures being major or minor embolism or haemorrhage. 2 patients in each group had major embolic events and 11 in each group had minor embolic events. The 95% confidence intervals on the differences are -3.4% to 3.2% for major embolism and -9.3% to 8.2% for minor embolism. Haemorrhagic complications were significantly more frequent with standard treatment (15 patients) than with the less intensive regimen (6 patients); and of the 5 patients with major haemorrhagic complications, all were in the standard treatment group, again a significant difference. The less intensive regimen is thus no less effective and safer than standard anticoagulant therapy in patients with tissue heart valve replacement.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Drug Evaluation; Embolism; Female; Heart Valves; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prothrombin Time; Random Allocation; Warfarin

A flexible loading dose schedule for inducing anticoagulation with warfarin was assessed in 31 consecutive patients. 55% reached the therapeutic range (prothrombin ratio between 2 and 4:1) by Day 2 (40 hours after the first dose) and this figure rose to 77% on Day 3 and to 87% on Day 4. All patients had a PTR between 1.7 and 4.2 on Day 5. Patients with evidence of cardiac failure and abnormal liver function, and those taking medications known to interact with warfarin required lower doses and ran a higher PTR when compared with the total group of patients. This schedule offers a useful means of safely and rapidly inducing warfarin therapy in all patients.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Embolism; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Thrombophlebitis; Warfarin

Topics: Clinical Trials as Topic; Echocardiography; Embolism; Heart Diseases; Heparin; Humans; Myocardial Infarction; Retrospective Studies; Thrombosis; Warfarin

Topics: Adult; Aortic Valve; Atrial Fibrillation; Dipyridamole; Embolism; Female; Follow-Up Studies; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Placebos; Postoperative Complications; Thromboembolism; Warfarin

Oral anticoagulants (OACs) mitigate stroke and systemic embolism (SE) risk in non-valvular atrial fibrillation (AF) patients but can increase the risk of major bleeding (MB). This study analyzed the gains in event-free time for these outcomes among OAC treatment options represented in the ARISTOPHANES study.. This sub-analysis consisted of NVAF patients who initiated warfarin, apixaban, dabigatran, or rivaroxaban from 01JAN2013-30SEP2015, with data pooled from Medicare and 4 US commercial claims databases. Propensity score matching was conducted between non-vitamin K antagonist OAC (NOAC) and warfarin cohorts in each database and results were pooled. Laplace regression was used to evaluate the delay in time to stroke/SE and MB events between NOACs and warfarin and between NOACs after the first 12-months of follow-up.. The population included 466,991 patients (167,413 warfarin; 108,852 apixaban; 37,724 dabigatran; and 153,002 rivaroxaban). Event-free time gain (95% confidence interval) for apixaban versus warfarin was 101 days (78- 124) for stroke/SE and 116 (103- 130) days for MB. The gain in event-free time for dabigatran versus warfarin was 45 days (3- 87) for stroke/SE and 92 (68- 116) days for MB. The gain in event-free time for rivaroxaban versus warfarin was 63 days (42- 84) for stroke/SE but event-free time decreased by 18 (-31-6) days for MB.. Over 12 months after initiation, apixaban and dabigatran conferred progressive increases in event free time for stroke/SE and MB vs warfarin, whereas rivaroxaban conferred an increase in stroke/SE-free time but a loss in MB-free time vs warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Medicare; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs).. Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models.. Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs.. Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Medicare; Multimorbidity; Pyridones; Risk Assessment; Rivaroxaban; Stroke; United States; Warfarin

Background We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. Conclusions In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Pressure; Critical Pathways; Embolism; Female; Heart Failure; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear.. We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders.. Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46-0.90]) or apixaban (HR, 0.40 [95% CI, 0.19-0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47-1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91-3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58-0.82]), apixaban (HR, 0.60 [95% CI, 0.46-0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62-1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18-2.14]).. Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Embolism; Hemorrhage; Humans; Ischemic Stroke; Liver Diseases; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

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

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Embolism; Humans; Risk Factors; Warfarin

Coronary embolism is a relatively rare but important non-atherosclerotic cause of acute coronary syndrome, mainly caused by atrial fibrillation and mechanical heart valve thrombosis due to subtherapeutic anticoagulation. There have been increasing reports of bioprosthetic valve thrombosis (BPVT), but thromboembolic events are rare and mainly affect the cerebrovascular system. Coronary embolism is an extremely rare complication of BPVT.. A 64-year-old male presented with non-ST-Elevation myocardial infarction (NSTEMI) to an Australian regional health service. Three years ago, he had undergone Bentall procedure with bioprosthetic aortic valve replacement for severe aortic regurgitation and significant aortic root dilatation. Diagnostic coronary angiography revealed embolic occlusion of first diagonal branch in the absence of underlying atherosclerosis. Prior to NSTEMI presentation, the patient was clinically asymptomatic apart from the progressive increase in transaortic mean pressure gradient on transthoracic echocardiography which was first detected seven months after surgical aortic valve replacement. Transoesophageal echocardiography showed restrictions of the aortic leaflet opening but no evidence of mass or vegetation. After eight weeks of warfarin therapy, the raised aortic valve gradient returned to normal. Lifelong warfarin was prescribed, and patient remained clinically well at 39-month follow-up.. We experienced a case of coronary embolism in a patient with probable BPVT. Reversible bioprosthetic valve hemodynamic deterioration after anticoagulation strongly supports the diagnosis in the absence of histopathology. Early moderate-to-severe hemodynamic valve deterioration warrants further investigations, including cardiac computed tomography and sequential echocardiography, to investigate for probable BPVT and consideration of timely anticoagulation initiation to prevent thromboembolic events.

Topics: Anticoagulants; Aortic Valve; Australia; Bioprosthesis; Coronary Artery Disease; Embolism; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Thromboembolism; Thrombosis; Warfarin

To investigate the efficacy and safety outcomes of warfarin and direct oral anticoagulants in Asian octogenarians. A retrospective study was undertaken in 270 patients aged 80 years old and above, between 15 July 2015 and 21 December 2017, prescribed oral anticoagulation (OAC) with warfarin or direct oral anticoagulant (DOAC). Data collection included demographics, bleeding events, cessation of anticoagulation, mortality and hospital utilization up to 2 years post prescription. Thrombotic and embolic events within 30 days of anticoagulation cessation were reviewed. Data was analysed according to initial prescription of either warfarin or DOAC. There were 134 patients on warfarin and 136 patients on DOAC, of which majority of them were on anticoagulation for atrial fibrillation. In the warfarin group, there was a higher rate of minor bleeding events leading to permanent cessation (12.7 vs. 2.9%, P  = 0.035) compared with DOAC. Mortality rate at 2 years was higher in the warfarin group than DOAC (40.3 vs. 28.7%, P  = 0.044). There was no difference in major bleeding events, risk of gastrointestinal bleed or ICH between the two groups. There was no difference in rate of thrombotic and embolic events after cessation of anticoagulation and hospital utilization over 2 years was similar in both groups. In Asian octogenarians on anticoagulation, DOAC appears to have benefit over warfarin in terms of minor bleeding risk and mortality.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Gastrointestinal Hemorrhage; Humans; Octogenarians; Retrospective Studies; Stroke; Warfarin

Harrington J, Carnicelli AP, Hua K, et al.

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

Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding.. Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Fibrinolytic Agents; Hemorrhage; Humans; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed.Methods and Results:In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer.. Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Neoplasms; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

The risk of bleeding and stroke/systemic embolism (SE) events associated with apixaban vs. warfarin among oral anticoagulant-naïve Japanese patients with non-valvular atrial fibrillation (NVAF) has not been well studied in daily clinical practice.Methods and Results:Clinical data for 12,090 patients were retrospectively extracted from the medical records of patients with NVAF (aged ≥20 years, creatinine clearance [CrCl] ≥15 mL/min) newly initiated to apixaban or warfarin treatment between January 1, 2010, and December 31, 2017, at 315 general practitioner clinics and 87 hospitals across Japan. After applying propensity score matching, patient characteristics were well-balanced between the apixaban and warfarin groups (4,523 patients each). The incidence rate (per 100 person-years) of major bleeding was lower in the apixaban vs. warfarin group (1.17 vs. 1.64; hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54-0.93; P=0.01), as was that of stroke/SE (1.14 vs. 1.73; HR, 0.65; 95% CI, 0.50-0.85; P<0.01). When patients were stratified by CrCl (≥50 mL/min and <50 mL/min), the P value for interaction was not statistically significant between subgroups (P=0.31 for major bleeding and P=0.32 for stroke/SE).. The benefit of apixaban over warfarin for the reduction in risk of major bleeding and stroke/SE could be generalizable to daily clinical practice and to patients with reduced renal function.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Japan; Pyrazoles; Pyridones; Retrospective Studies; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Dabigatran; Embolism; Hemorrhage; Humans; Risk Factors; Stroke; Warfarin

Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications.. This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m. A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups.. In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Obesity; Polypharmacy; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Hemoglobin levels and platelet counts have been associated with adverse clinical outcomes in patients with cardiovascular conditions. We aimed to assess the impact of oral anticoagulant use for patients with atrial fibrillation and concomitant anemia or thrombocytopenia.. We used medical data from a multicenter health care system in Taiwan including 37,074 patients with atrial fibrillation. Patients were categorized into 3 groups based on hemoglobin and platelet levels: Group 1 (hemoglobin >10g/dL and platelet>100 K/µL; n = 29,147), Group 2 (hemoglobin<10 g/dL or platelet<100 K/µL; n = 7078), and Group 3 (hemoglobin <10 g/dL and platelet <100 K/µL; n = 849). Patients in each category were further stratified as 3 groups according to their stroke prevention strategies: no oral anticoagulant use (non-OAC), warfarin, or nonvitamin K antagonist oral anticoagulants (NOACs).. A higher hemoglobin or platelet level was associated with a higher risk of ischemic stroke/systemic embolism but lower risks of intracranial hemorrhage and major bleeding. The composite risks of ischemic stroke/systemic embolism, intracranial hemorrhage and major bleeding were higher in Group 3 or Group 2, compared with Group 1 (6.79% a year vs 6.41% year vs 4.13% year). Compared to non-OACs, warfarin was not associated with a lower composite risk in the 3 groups. NOACs were associated with a lower composite risk in Group 1 (adjusted hazard ratio:0.68, [95% confidence interval:0.60-0.76]) and Group 2 (adjusted hazard ratio:0.73, [95% confidence interval:0.53-0.99]) but was nonsignificant in Group 3.. Patients with atrial fibrillation with anemia or thrombocytopenia were a high-risk population. Compared with no OAC use, NOACs were associated with better clinical outcomes for patients with atrial fibrillation and advanced anemia (hemoglobin <10g/dL) or thrombocytopenia (platelet <100 K/µL) but not for those with both conditions.

Topics: Administration, Oral; Anemia; Anticoagulants; Atrial Fibrillation; Embolism; Hemoglobins; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Risk Factors; Stroke; Thrombocytopenia; Warfarin

We determined the long-term event incidence among elderly patients with nonvalvular atrial fibrillation in terms of history of stroke/transient ischemic attack (TIA) and oral anticoagulation.. Patients aged ≥75 years with documented nonvalvular atrial fibrillation enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were divided into 2 groups according to history of stroke/TIA. The primary end point was the occurrence of stroke/systemic embolism within 2 years, and secondary end points were major bleeding and all-cause death within 2 years. Cox models were used to determine whether there was a difference in the hazard of each end point in patients with/without history of stroke/TIA, and in ischemic stroke/TIA survivors taking direct oral anticoagulants versus those taking warfarin.. Of 32 275 evaluable patients (13 793 women [42.7%]; median age, 81.0 years), 7304 (22.6%) had a history of stroke/TIA. The patients with previous stroke/TIA were more likely to be male and older and had higher hazard rates of stroke/systemic embolism (adjusted hazard ratio, 2.25 [95% CI, 1.97-2.58]), major bleeding (1.25, 1.05-1.49), and all-cause death (1.13, 1.02-1.24) than the other groups. Of 6446 patients with prior ischemic stroke/TIA, 4393 (68.2%) were taking direct oral anticoagulants and 1668 (25.9%) were taking warfarin at enrollment. The risk of stroke/systemic embolism was comparable between these 2 groups (adjusted hazard ratio, 0.90 [95% CI, 0.71-1.14]), while the risk of major bleeding (0.67, 0.48-0.94), intracranial hemorrhage (0.57, 0.39-0.85), and cardiovascular death (0.71, 0.51-0.99) was lower among those taking direct oral anticoagulants.. Patients aged ≥75 years with nonvalvular atrial fibrillation and previous stroke/TIA more commonly had subsequent ischemic and hemorrhagic events than those without previous stroke/TIA. Among patients with previous ischemic stroke/TIA, the risk of hemorrhagic events was lower in patients taking direct oral anticoagulants compared with warfarin.. URL: https://www.. gov; Unique Identifier: UMIN000024006.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis.. Retrospective cohort study.. Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin.. First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin.. Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality.. Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring.. Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses.. Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding.. Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Embolism; Hemorrhage; Humans; Medicare; Renal Dialysis; Retrospective Studies; Risk Assessment; Stroke; United States; Warfarin

The aim of this study was to compare outcomes among patients from the PROTECT-AF (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Evaluation of the WATCHMAN Left Atrial Appendage [LAA] Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) left atrial appendage occlusion (LAAO) trials with matched patients from the National Cardiovascular Data Registry LAAO Registry using patient-level data.. Patients undergoing LAAO in clinical practice generally have more comorbidities than trial participants.. Propensity-matched analyses, with up to 3 registry patients matched to each trial patient, were performed using Cox proportional hazards and Fine-Gray models.. A total of 1,904 registry patients were matched to 667 trial LAAO patients; 1,010 registry patients were matched to 348 warfarin patients. Compared with registry patients, trial LAAO patients experienced more pericardial effusion requiring intervention (3.8% vs 0.6%, P < 0.001), periprocedural ischemic stroke (0.9% vs 0.2%, P = 0.005), and failed device implantation (7.5% vs 3.6%, P < 0.001). The 425-day risk of ischemic stroke in trial LAAO patients was higher than in registry patients (2.70% vs 1.21%; HR: 1.951; P = 0.03); warfarin patients had comparable rates of ischemic stroke compared with registry patients (1.15% vs 1.29%; HR: 0.728; P = 0.57). Hemorrhagic stroke risk was similar among trial LAAO and registry patients (P = 0.88). Hemorrhagic stroke risk was greater among warfarin patients versus registry patients (1.44% vs 0.20%; HR: 5.871, P = 0.03). Mortality was lower in trial LAAO patients than in registry patients (2.92% vs 6.23%; HR: 0.477; P = 0.004), a difference attributable to noncardiovascular deaths. Mortality was similar (P = 0.44) among trial warfarin (4.48%) and registry (5.86%) patients.. In clinical practice, patients who meet trial criteria and undergo LAAO experience a lower risk of ischemic stroke, a similar risk of hemorrhagic stroke, and a higher risk of death after implant versus LAAO trial patients. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation [PROTECT-AF], NCT00129545; Evaluation of the WATCHMAN Left Atrial Appendage [LAA] Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy [PREVAIL], NCT01182441).

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Clinical Trials as Topic; Embolism; Hemorrhagic Stroke; Humans; Ischemic Stroke; Treatment Outcome; Warfarin

There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding.. This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB.. A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated with apixaban, 12,500 (5.1%) with dabigatran, 38,246 (15.6%) with rivaroxaban, and 138,723 (56.7%) with warfarin. Apixaban (hazard ratio [HR]: 0.76 [95% CI: 0.70, 0.83]) and rivaroxaban (HR: 0.79 [95% CI: 0.71, 0.87]) had a lower risk of stroke/SE vs. warfarin. Apixaban (HR: 0.67 [95% CI: 0.64, 0.70]) and dabigatran (HR: 0.88 [95% CI: 0.81, 0.96]) had a lower risk of MB vs. warfarin. Apixaban patients had a lower risk of stroke/SE vs. dabigatran (HR: 0.70 [95% CI: 0.57, 0.86]) and rivaroxaban (HR: 0.85 [95% CI: 0.76, 0.96]) and a lower risk of MB than dabigatran (HR: 0.73 [95% CI: 0.67, 0.81]) and rivaroxaban (HR: 0.64 [95% CI: 0.61, 0.68]).. In this real-world analysis of a large sample of NVAF patients with prior bleeding, NOACs were associated with similar or lower risk of stroke/SE and MB vs. warfarin and variable risk of stroke/SE and MB against each other.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

To investigate effects of appropriately and inappropriately dosed apixaban/rivaroxaban versus warfarin on effectiveness and safety outcomes in patients with non-valvular atrial fibrillation (NVAF).. Cohort study with nested case-control analyses using primary care electronic health records (IQVIA Medical Research Data UK database).. UK primary care.. Patients aged ≥18 years with NVAF newly prescribed apixaban (N=14 701), rivaroxaban (N=14 288) or warfarin (N=16 175) between 1 January 2012 and 30 June 2018, and followed up to 31 December 2018.. Incident cases of ischaemic stroke/systemic embolism (IS/SE) and intracranial bleeding (ICB). Cases were matched to controls on age, sex and OAC naïve status. Using logistic regression, adjusted ORs with 95% CIs were calculated for the outcomes comparing apixaban/rivaroxaban use (appropriate or inappropriate dosing based on the product label criteria) and warfarin.. For IS/SE, ORs (95% CIs) for apixaban versus warfarin were 1.19 (0.92-1.52) for appropriate dose and 1.01 (0.67-1.51) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 1.07 (0.83-1.37) for appropriate dose and 1.21 (0.78-1.88) for inappropriate dose. For ICB, ORs (95% CIs) for apixaban versus warfarin were 0.67 (0.44-1.00) for appropriate dose and 0.45 (0.21-0.95) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 0.81 (0.55-1.20) for appropriate dose and 1.14 (0.56-2.31) for inappropriate dose.. Dosing appropriateness in NVAF was not associated with a significant difference in IS/SE risk or increase in ICB risk versus warfarin. These findings may reflect residual confounding and biases that were difficult to control, as also seen in other observational studies. They should, therefore, be interpreted with caution, and prescribers should adhere to the dosing instructions in the respective Summary of Product Characteristics. Further studies on this topic from real-world populations are needed.

Topics: Adolescent; Adult; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Cohort Studies; Embolism; Humans; Intracranial Hemorrhages; Ischemic Stroke; Primary Health Care; Pyrazoles; Pyridones; Rivaroxaban; United Kingdom; Warfarin

Non-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown.. We retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death.. The mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56-2.34), major bleeding (HR 0.80, 95% CI 0.32-2.03) and all-cause death (HR 1.09, 95% CI 0.73-1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76-1.47). These outcomes were not different in various subgroups analyzed.. In this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; Ischemic Stroke; Male; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

To observe the safety and efficacy of warfarin and rivaroxaban in anticoagulation therapy in patients with atrial fibrillation (AF).. A total of 96 patients with AF treated in our hospital from June 2019 to February 2021 were enrolled in this study. According to the different modes of drug administration, the patients were divided into the warfarin group and rivaroxaban group. Demographic and clinical data such as age, body weight, and previous drug use were collected. The blood routine, liver and kidney function, blood coagulation routine, and cardiac color ultrasound were accessed. The valvular atrial fibrillation and anticoagulant taboos were excluded, and the risk of embolism and bleeding was evaluated. Among them, 48 patients in the warfarin group were given warfarin once a day, and the international ratio (INR) was used to adjust the dose, and the INR was controlled between 2.0 and 3.0. In contrast, 48 patients in the rivaroxaban group received a fixed dose of rivaroxaban 20 mg or 15 mg once a day. After administration, regular telephone or outpatient follow-up was given once a month, to monitor patients' drug compliance and ask if there was bleeding, and to detect blood routine, urine routine, fecal routine+occult blood, and liver and kidney function. In addition, at the beginning of 3, 6, and 12 months of follow-up, each patient was given cardiac color Doppler ultrasound, peripheral vascular color ultrasound, and brain CT to determine whether there were mural thrombosis, stroke, and peripheral arterial thromboembolism. The INR attainment rate, coagulation index, thromboembolism, bleeding, and adverse reactions were compared between the two groups.. There was no significant difference in serum Dmurd and NT-proBNP levels between the two groups before treatment and 3, 6, and 9 months after treatment. There was no significant difference in the number of venous embolism, pulmonary embolism, cerebral embolism, and total embolism between the two groups (. Compared with warfarin, rivaroxaban anticoagulant therapy has the same advantage in tolerance and prevention of thromboembolism in patients with AF, but rivaroxaban can effectively reduce the risk of bleeding in patients with AF.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome; Warfarin

This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged ≥75 years) Japanese population with non-valvular atrial fibrillation (NVAF).Methods and Results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anticoagulants [OACs]): 0-4 [38.8%], 5-8 [43.3%], and ≥9 [17.9%]). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events.. Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Embolism; Humans; Polypharmacy; Prospective Studies; Registries; Stroke; Warfarin

In the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA "closure." However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized.. We sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device.. Using combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5.. PDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291]).

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Echocardiography, Transesophageal; Embolism; Female; Humans; Male; Stroke; Thromboembolism; Treatment Outcome; Warfarin

To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients.. Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38-0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63-0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51-0.63) and dabigatran (HR = 0.80; 95% CI 0.70-0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07-1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs.. This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Medicare; Pyridones; Rivaroxaban; Stroke; United States; Warfarin

While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin.. This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death.. Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92-2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70-1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59-0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69-0.94]) compared to warfarin users.. Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Ischemic Stroke; Medicare; Neoplasms; Retrospective Studies; Stroke; Treatment Outcome; United States; Warfarin

To assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.. We identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.. Among 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA. In this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Rivaroxaban; Stroke; Warfarin

Using Scandinavian population-based registries, we assessed risk of stroke/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in anticoagulation-naïve patients with atrial fibrillation (AF).. This historical cohort study included 219 545 AF patients [median age 74 years; 43% women; mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65-74 years, sex category) score 3.3] initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden (1 January 2013 to 31 December 2016). The primary endpoints were stroke/SE and major bleeding. The median follow-up times were 9.7 (3.9-21.5) months for stroke/SE and 9.6 (3.8-21.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban-warfarin (n = 111 162), dabigatran-warfarin (n = 56 856), and rivaroxaban-warfarin (n = 61 198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke/SE, adjusted HRs against warfarin were 0.96 [95% confidence interval (CI): 0.87-1.06] for apixaban, 0.89 (95% CI: 0.80-1.00) for dabigatran, and 1.03 (95% CI: 0.92-1.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI: 0.67-0.78) for apixaban, 0.89 (95% CI: 0.82-0.97) for dabigatran, and 1.15 (95% CI: 1.07-1.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dose-defined subgroups.. In this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke/SE to patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Rivaroxaban; Stroke; Warfarin

To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes.. Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models.. A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09).. In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Embolism; Hemorrhage; Humans; Obesity; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

The populations included in the randomized controlled clinical trials and observational studies were different. The effectiveness and safety of rivaroxaban for stroke prevention in patients with atrial fibrillation (AF) varied among studies. This study aimed to estimate the real-world outcomes of rivaroxaban in patients with AF accurately. A discrete event simulation (DES) was used to predict the counterfactual results of the ROCKET AF study. The hypothetical cohorts of patients were generated using Monte Carlo simulation according to the baseline covariate distributions that matched the marginal distribution of covariates reported in the ROCKET AF and three observational studies. The DES model structure was constructed based on a priori knowledge about disease progression and possible outcomes of patients with AF. The DES model accurately replicated the overall results of the ROCKET AF study. Both predicted stroke/systematic embolism (SE) and major bleeding rates were lower in the three observational studies than in the simulated ROCKET AF study. The risk difference of stroke/SE and major bleeding was not significant among the predicted outcomes of the three observational studies. Although some differences existed in the absolute rates of stroke/SE and major bleeding between observed and simulated studies, the results confirmed that rivaroxaban was noninferior to warfarin for the prevention of stroke/systematic embolism with no significance in the risk of major bleeding in large AF populations, which was similar to the results of ROCKET AF.

Topics: Anticoagulants; Atrial Fibrillation; Computer Simulation; Embolism; Factor Xa Inhibitors; Humans; Monte Carlo Method; Observational Studies as Topic; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Evidence of clinical outcomes for oral anticoagulants and antiplatelet treatment (APT) in patients with atrial fibrillation (AF) and critical limb ischemia (CLI) is very limited.. In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, 1223 patients with AF and CLI taking direct-acting oral coagulants (DOACs), warfarin, or APT were identified from June 1, 2012, to December 31, 2017. We used propensity score stabilized weighting (PSSW) to balance covariates across study groups.. After PSSW, DOAC (n = 446) was associated with lower risks of ischemic stroke/systemic embolism (IS/SE), all major adverse limb events, and all major bleeding events compared with warfarin (n = 237). DOAC was associated with lower risks of IS/SE, acute myocardial infarction (AMI), and all major adverse limb events and a comparable risk of major bleeding events compared with APT (n = 540). DOAC has a lower risk of composite net-clinical-benefit outcome (IS/SE, AMI, all major adverse limb events, plus all major bleeding events) compared with warfarin (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.35-0.65; P < 0.0001) or APT (HR: 0.44; 95% CI: 0.34-0.56; P < 0.0001). The composite net-clinical-benefit outcome was comparable for warfarin vs APT. The reduced risk of net-clinical-benefit outcome for DOAC vs warfarin or APT persisted in high subgroups including age > 75 years, presence of diabetes mellitus, or chronic kidney disease.. DOAC was associated with a significantly lower risk of composite net-clinical-benefit outcome than either warfarin or APT in patients with AF and concomitant CLI. Further prospective study is necessary to validate the findings in the future.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Embolism; Extremities; Factor Xa Inhibitors; Hemorrhage; Humans; Ischemia; Ischemic Stroke; Platelet Aggregation Inhibitors; Retrospective Studies; Taiwan; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date.. COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771).. In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.

Topics: Academic Medical Centers; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Computer Security; Databases, Factual; Embolism; Female; Humans; Information Dissemination; Male; Multicenter Studies as Topic; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke; Warfarin

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Coronary Artery Disease; Dabigatran; Embolism; Female; Health Care Costs; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Peripheral Arterial Disease; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; United States; Warfarin

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Coronary Disease; Dabigatran; Diabetes Mellitus; Embolism; Female; Heart Failure; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Male; Medication Adherence; Middle Aged; Polypharmacy; Proportional Hazards Models; Stroke; Warfarin

Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited.. To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF.. New-user retrospective propensity score-matched cohort study.. U.S.-based commercial health care database from 1 January 2010 to 30 June 2019.. Adults with valvular AF who were newly prescribed DOACs or warfarin.. The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding.. Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]).. Relatively short follow-up; inability to ascertain disease severity.. In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF.. None.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Comparative Effectiveness Research; Dabigatran; Embolism; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Male; Propensity Score; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; Warfarin

Low dose direct acting oral anticoagulants (LDDOACS) were approved for elderly atrial Fibrillation (AF) patients with limited information. A retrospective analysis collecting baseline characteristics and outcomes in AF patients ≥ 80 prescribed LDDOAC or warfarin (W), from a multidisciplinary practice between 1/1/11 (First LDDOAC available) and 5/31/17 was conducted. From 9660 AF patients, 514 ≥ 80 received a LDDOAC and 422 W. A multivariable comparison found LDDOAC patients were older (p <0.001), had lower creatinine clearance (CrCl) (p = 0.006), used more anti-platelet drugs (p <0.001), and more often had new onset AF verses those prescribed W (p <0.001). There were no clinically significant differences among those patients receiving Dabigatran 75 mgs BID (D), Rivaroxaban 15mgs (R) or Apixaban 2.5mgs BID (A). Forty-eight and 50% of the patients remained on their LDDOAC or W for the observation period (p = 0.55). Stroke/systemic embolism (SSE) and CNS bleeds were 1.16 vs 2.22%/yr., (p = 0.143) and 1.46 vs 0.93%/yr., (p = 0.24). Mortality and major bleeds were 6.26 vs 1.67%/yr., and 12.3vs 3.77%/yr. (p <0.001). SSE were 1.1%/yr for D, R, and A (p = 0.94). CNS bleeds were 2.2 for D, 1.7 for R and 0.8%/yr. for A: p = 0.53. Major bleeding was: 14.3 for D, 14.1 for R and 9.1%/yr. for A, p = 0.048 (with A < R, p = 0.01). Mortality was 5.5 for D, 4.2 for R and 9.5% for A, p = 0.031. In conclusion, half the patients remained on their assigned anti-coagulant. SSE and intracranial bleed rates were similar and low. Major bleeds and deaths were different between groups emphasizing the need for prospective randomized trials in this growing population with AF.

Topics: Age Factors; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Both time in therapeutic range (TTR) for anticoagulation and depression are associated with dementia risk. The purposes of this study were to examine the impact of depression on TTR and to describe the partitioned contribution of depression and TTR on long-term dementia risk. We studied 14,953 patients anticoagulated with warfarin (target INR 2-3) for atrial fibrillation (AF), venous thromboembolism (VTE), or a mechanical heart valve from 2003 to 2015. We excluded patients with a diagnosis of dementia before or within 6 months of warfarin initiation. We examined the association of depression with TTR using finite mixture modeling and logistic regression and utilized multivariable Cox hazard regression to determine the association of TTR and depression with incident dementia at 3 and 13 years. Forty % (n = 6055) of patients were diagnosed with depression before or while on warfarin. Patients with depression had significantly lower TTR and were 1.37 times more likely to have TTR <50% than non-depressed patients (p <0.0001). During follow-up, 4.2% of patients received the diagnosis of dementia within 3 years as compared to 12% during all-time follow up. The 3-year risk of dementia was highest for patients with a ≤50% TTR regardless of depression status. The 3-year dementia risk was associated with TTR (p <0.0001) but not depression. However, for all-time dementia both TTR (p <0.0001) and depression (p <0.0001) as well as their interaction (p = 0.049) were associated with dementia. Depression increased the risk of long-term dementia by 1.69 fold (95% CI: 1.33, 2.15) for patients with the lowest TTR. Depression is prevalent in patients managed with warfarin and is associated with significant decreases in TTR. In conclusion, decreased TTR appears to increase 3-year dementia risk and both low TTR and depression interact to increase risk for all-time dementia in patients taking warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dementia; Depression; Embolism; Female; Heart Valve Prosthesis; Humans; Incidence; International Normalized Ratio; Logistic Models; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stroke; Time Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug-drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7-28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51-2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56-3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97-4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dicloxacillin; Drug Interactions; Embolism; Female; Floxacillin; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Penicillin V; Registries; Stroke; Warfarin; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Embolism; Health Expenditures; Humans; Ischemic Stroke; Japan; Models, Econometric; Myocardial Infarction; Quality-Adjusted Life Years; Rivaroxaban; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dicloxacillin; Embolism; Floxacillin; Heart Valves; Humans; Ischemic Stroke; Stroke; Warfarin

Data on real-world antiarrhythmic and anticoagulant therapy use in elderly atrial fibrillation (AF) patients are lacking; thus, we performed a subanalysis of data from the ANAFIE registry to clarify the current management of Japanese patients aged ≥75 years with non-valvular AF.. The ANAFIE registry was a multicenter, prospective, observational study. Patients were stratified into three groups: rhythm control group, rate control group, and no antiarrhythmic group. The CHADS. Among 32,490 patients, the overall frequencies of AF by type were 42.0 % (paroxysmal), 30.1 % (persistent and long-standing persistent), and 27.9 % (permanent). Significant differences (p < 0.0001, each) in age were observed among the three groups; more patients aged 75-79 years received rhythm control (44.2 %) vs rate control (38.8 %). Patients aged ≥85 years received either rate control therapy or no antiarrhythmic agent (∼20 %, each). In the overall population, 36.9 % and 19.6 % of patients were receiving rate and rhythm control therapy, respectively; 43.4 % were not receiving antiarrhythmic therapy. The rate control group consisted mainly of patients with persistent (16.3 %) and permanent AF (38.6 %), and the rhythm control group, of patients with paroxysmal AF (79.0 %). Significantly lower embolic and bleeding risk scores and significantly higher embolic risk scores were observed in patients in the rhythm and rate control groups, respectively. In total, 92.1 % of elderly Japanese patients with AF were receiving anticoagulant therapy. The frequency of direct-acting oral anticoagulant (DOAC) use was similar (∼66 %) among the three groups. Significantly more patients in the rate control group (28.6 %) were being treated with warfarin than in the rhythm control group (21.6 %) (p < 0.0001).. Use versus non-use and antiarrhythmic therapy varied significantly by age, stroke risk scores, type of AF, and DOAC use between subgroups.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; Japan; Male; Registries; Risk Factors; Warfarin

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Cross-Sectional Studies; Embolism; Female; Humans; Kenya; Male; Middle Aged; Prevalence; Tertiary Care Centers; Venous Thromboembolism; Warfarin

Oral anticoagulants (OACs) are high-priority medications, frequently used with clinically important benefit and serious harm. Our objective was to compare the safety and effectiveness of direct-acting oral anticoagulants (DOACs) versus warfarin in a population where anticoagulation management and DOACs were readily available. A retrospective cohort study of all adults living in British Columbia with a diagnosis of atrial fibrillation and a first prescription for an OAC was conducted. Co-primary outcomes were ischemic stroke and systemic embolism, and major bleeding. Secondary outcomes included a net clinical outcome composite and analysis of discontinuation, switching, and key subgroups. We estimated the effects of treatment using time-to-event models with high-dimensional propensity score adjustment to control confounding. After adjustment for prescribing bias, a cohort (n = 20,113, 43.8% female, mean age 72.4 years) with a mean follow-up of 18.1 months showed that patients taking warfarin tended to be poorer, sicker, and less likely to have a cardiologist prescriber. Outcome event rates were not significantly different for DOACs compared to warfarin [adjusted rate ratio of 1.15 (0.91, 1.46) for systemic embolism, 0.94 (0.82, 1.08) for major bleeding, and 0.98 (0.90, 1.06) for net clinical outcome]. Only the effect of age on net clinical outcome met our strict criteria for predicting which group might be superior. Switch of drug class was associated with increased risk of events (p < 0.003). In this population, we found no difference in important clinical outcomes between warfarin and DOACs. Switching compared to not switching was associated with harm.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; British Columbia; Cohort Studies; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

To address gaps in the data comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among patients with nonvalvular atrial fibrillation (NVAF) and diabetes.. A retrospective study was conducted on patients with NVAF and diabetes newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with Medicare data from the US Centers for Medicare & Medicaid Services and 4 other US commercial claims databases. One-to-one propensity score matching was completed between NOACs and warfarin and between NOACs in each database, and the results were pooled. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB).. A total of 154,324 patients were included in the 6 matched cohorts, with a mean follow-up time of 6 to 8 months. Compared with warfarin, apixaban (hazard ratio [HR], 0.67; 95% CI, 0.57-0.77) and rivaroxaban (HR, 0.79; 95% CI, 0.71-0.89) were associated with a lower risk of stroke/SE; dabigatran (HR, 0.84; 95% CI, 0.67-1.07) was associated with a similar risk of stroke/SE. Apixaban (HR, 0.60; 95% CI, 0.56-0.65) and dabigatran (HR, 0.78; 95% CI, 0.69-0.88) were associated with a lower risk of MB; rivaroxaban (HR, 1.02; 95% CI, 0.94-1.10) was associated with a similar risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of MB. Compared with rivaroxaban, dabigatran was associated with a lower risk of MB.. This study-the largest observational study to date of patients with NVAF and diabetes taking anticoagulants-found that NOACs were associated with variable rates of stroke/SE and MB compared with warfarin.. clinicaltrials.gov Identifier: NCT03087487.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Complications; Embolism; Hemorrhage; Humans; Retrospective Studies; Risk Assessment; Stroke; Treatment Outcome; Warfarin

Black patients are under-represented in randomized trials evaluating oral anticoagulants in non-valvular atrial fibrillation (NVAF). We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in African Americans with NVAF.. We performed an analysis using Optum® De-Identified Electronic Health Record (EHR) data from 1/1/2012-9/30/2018. We included adult African American patients with a diagnosis of NVAF who were anticoagulant-naïve during the 12-months prior to initiation of rivaroxaban or warfarin. Patients receiving rivaroxaban were 1:1 propensity score matched to warfarin patients. Our primary effectiveness and safety outcomes were the 2-year incidence rates (%/year) of stroke or systemic embolism (SSE) and major bleeding using an intention-to-treat approach. Cohorts were compared using doubly-robust Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. We matched 4102 rivaroxaban and 4102 warfarin users with a median (interquartile range) available follow-up of 2.0 (0.9, 2.0) years. Median CHA2DS2-VASc and HASBLED scores were 3 (2, 4) and 2 (1, 3). Rivaroxaban use was associated with a lower risk of SSE (1.99 versus 2.48, HR = 0.77, 95%CI = 0.60-0.99), ischemic stroke (1.84 versus 2.37, HR = 0.76, 95%CI = 0.59-0.98) and major bleeding (4.22 versus 4.98, HR = 0.84, 95%CI = 0.70-0.99). No differences in intracranial hemorrhage or gastrointestinal bleeding were observed. Neither sensitivity analyses utilizing an on-treatment methodology nor inverse probability-of-treatment weighting showed significant differences in SSE or major bleeding between rivaroxaban and warfarin users.. Rivaroxaban appeared at least as effective and safe as warfarin when used to manage African American patients with NVAF in routine practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Black or African American; Embolism; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

To compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non-inferiority trial by rigorously mimickingin an observational study the trial's design features.. This cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate 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) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non-inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention-to-treat [ITT], per-protocol [PP], and as-treated populations) using a hazardratio (HR) of 1.46 as the non-inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox-proportional hazard analyses.. We included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non-inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95%CI 0.84 to 1.30) (ITT), HR=0.98 (95%CI 0.70 to 1.38) (PP), and HR=1.11 (95%CI 0.86 to 1.42) (as-treated). Risk of major bleeding was also similar to the target trial.. The results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non-inferiority trial to assess drug effectiveness.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation.. This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated.. Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran.. Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Rivaroxaban; Stroke; Warfarin

In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage.. We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations.. We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01-7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63-2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29-0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22-1.48]).. Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Embolism; Female; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Neuroimaging; Recurrence; Registries; Retrospective Studies; Risk Assessment; Stroke; Treatment Outcome; United States; Warfarin

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

To evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.. A total of 76 019 individuals with AF were identified in England in 1998-2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02-1.24), 1.20 (1.05-1.36), and 1.27 (1.19-1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.. Prevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Cardiac Valve Annuloplasty; Cause of Death; Embolism; England; Factor Xa Inhibitors; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhagic Stroke; Humans; Ischemic Stroke; Male; Middle Aged; Mortality; Phenotype; Prevalence; Prognosis; Proportional Hazards Models; Stroke; Warfarin

Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial.. A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced.. Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment.. In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Embolism; Female; Humans; Male; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

BACKGROUND Whether ablation therapy reduces the risk of death and embolic events in elderly patients with atrial fibrillation (AF) remains unclear. MATERIAL AND METHODS AF patients ≥65 years old receiving either catheter ablation or non-ablation therapy at 2 tertiary and 2 non-tertiary hospitals in Beijing from November 2009 to December 2012 were enrolled. Patients were followed up every 6 months for information on treatment and clinical event occurrence. A propensity score matching algorithm produced comparable 2 groups of patients treated with ablation or non-ablation. Rates of a composite of all-cause death, non-fatal stroke, and peripheral embolism were the primary outcomes. Each composite component and major bleeding were the secondary outcomes. RESULTS There were 596 ablated patients and 1144 patients with non-ablation therapy enrolled. Propensity score algorithm matched 347 comparable pairs of patients. Patient characteristics variables were well balanced. During 523.5 and 497.5 patient-years follow-up, respectively, ablation therapy was associated with a significant lower risk of experiencing the primary composite outcome (hazard ratio [HR]=0.40; 95% confidence interval [CI]: 0.19-0.85), all-cause death (HR=0.13 95% CI: 0.04-0.43), and major bleeding (HR=0.23; 95% CI: 0.12-0.67), without apparent heterogeneity by age, sex, and AF type, and for risk score subgroups. CONCLUSIONS In this propensity-matched elderly sample, ablation therapy was associated with lower risk of composite outcome consisting of all-cause death, non-fatal stroke, and peripheral embolism, and therefore might be an alternative to conservative therapy.

Topics: Aged; Aged, 80 and over; Algorithms; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Embolism; Female; Humans; Male; Propensity Score; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

To compare the effectiveness and safety of standard-dose rivaroxaban (20 mg o.d.) and warfarin in non-valvular atrial fibrillation (NVAF) patients with a non-sex-related CHA2DS2-VASc score of 1.. Analysis of United States Truven MarketScan claims from November 2011 to December 2016 for anticoagulant-naïve NVAF patients with a single non-sex-related stroke risk factor assigned 1-point in the CHA2DS2-VASc score and ≥12-months of continuous medical/prescription insurance coverage prior to the qualifying oral anticoagulant dispensing. Standard-dose rivaroxaban users were 1:1 propensity score-matched to warfarin users. Patients were followed until outcome occurrence, insurance disenrollment, or end of data availability. Primary outcomes included stroke or systemic embolism and major bleeding and were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). In all, 3319 rivaroxaban users were 1:1 propensity score-matched to 3319 warfarin users. Median (interquartile range) duration of follow-up was 1.6 (0.7, 2) years and the most common qualifying stroke risk factor was hypertension (n = 4532, 68.3%). Rivaroxaban was associated with a significant reduction in the 1-year stroke or systemic embolism vs. warfarin (HR 0.41, 95% CI 0.17-0.98), with no significant difference in overall major bleeding (HR 0.74, 95% CI 0.44-1.26) or major bleeding subtypes (HR ranging from 0.33 to 0.78, P > 0.05 for all). Similar results were seen after extending follow-up to 2 years.. Rivaroxaban may lower the rate of stroke or systemic embolism vs. warfarin in NVAF patients with a non-sex-related CHA2DS2-VASc score of 1 without impacting major bleeding.

Topics: Administrative Claims, Healthcare; Anticoagulants; Atrial Fibrillation; Databases, Factual; Decision Support Techniques; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

Antithrombotic therapy, including direct oral anticoagulants, is recommended in patients with non-valvular atrial fibrillation (NVAF) who are at intermediate-to-high risk of stroke. The aims of this study were to assess the patterns of oral anticoagulant (OAC) prescription in Japanese patients with NVAF and compare the effectiveness and safety of dabigatran and warfarin.. This was a retrospective observational study of adults with NVAF who initiated dabigatran or warfarin between March 14, 2011 and June 30, 2016, using electronic claims data of approximately 12.94 million patients from 230 hospitals. Propensity score matching was used to derive equal patient cohorts. Outcomes included the combined incidence of stroke, systemic embolism, and intracranial bleeding (primary endpoint) and the incidence of major bleeding (secondary endpoint).. Overall, 400,884 patients were included. Among those prescribed an OAC, warfarin was the most common (34.3%). For the comparison of dabigatran and warfarin, 4606 patients were propensity-score matched in each cohort. Dabigatran recipients had lower incidences of stroke, systemic embolism, and intracranial bleeding [29.0 vs. 35.6 per 1000 patient-years; hazard ratio (HR), 0.72; 95% confidence interval (CI): 0.53-0.97; p=0.031] and major bleeding (6.4 vs. 11.3 per 1000 patient-years; HR, 0.55; 95% CI: 0.30-0.99; p=0.048). The most common type of bleeding in both groups was gastrointestinal and the incidence was lower in dabigatran recipients (1.6 vs. 6.4 per 1000 patient-years; HR, 0.24; 95% CI: 0.08-0.69; p=0.009).. In Japan, dabigatran was associated with a lower risk of stroke, systemic embolism, and intracranial bleeding and major bleeding compared with warfarin in patients with NVAF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comparative Effectiveness Research; Dabigatran; Databases, Factual; Embolism; Female; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Japan; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

To investigate the roles of microembolus and plasma D-dimer in evaluating the warfarin anticoagulant therapy efficacies for patients with atrial fibrillation (AF).. Fifty-six AF patients were treated with aspirin antiplatelet therapy (Group ASP) and forty AF patients were treated with warfarin anticoagulant therapy (Group WAR). The microemboli and plasma D-dimer in these two groups were monitored and compared before and after treatment.. Group ASP had 21 and 17 cases with positive microemboli before and after treatment, respectively, and there was no significant difference in the detection rate of microemboli before and after treatment; Group WAR had 14 and 5 cases with positive microemboli before and after treatment, respectively, and the detection rate of microemboli was significantly reduced after treatment. The levels of plasma D-dimer in the two groups were significantly reduced after treatment (327±73 µg/L vs 235±61 µg/L and 313±81 µg/L vs 170±67 µg/L, respectively, P<0.05), among which the reduction level in Group WAR was more significant.. Microemboli and D-dimer can be used as the indicators for evaluating the embolism risk and therapeutic efficacies in AF patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Dose-Response Relationship, Drug; Embolism; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

Patients with nonvalvular atrial fibrillation with stage 4 or 5 chronic kidney disease or undergoing hemodialysis were excluded from phase III randomized trials of nonvitamin K antagonist oral anticoagulants (NOACs). We sought to evaluate the effectiveness and safety of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation and stage 4 or 5 chronic kidney disease or undergoing hemodialysis in routine practice.. Using MarketScan data from January 2012 to December 2017, we identified patients on oral anticoagulant (OAC) with naïve nonvalvular atrial fibrillation and stage 4 or 5 chronic kidney disease or undergoing hemodialysis and with ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between the rivaroxaban and warfarin cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores calculated using generalized boosted models and 10,000 regression trees (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a stroke/systemic embolism or major bleeding event, OAC discontinuation/switch, insurance disenrollment, or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the OAC cohorts were calculated using Cox regression.. We identified 1896 rivaroxaban (38.7% received a dose <20 mg/d) and 4848 warfarin users. Eighty-eight percent of included patients had stage 5 chronic kidney disease or were undergoing hemodialysis. Rivaroxaban did not significantly reduce stroke or systemic embolism (HR = 0.55, 95% CI = 0.27-1.10) or ischemic stroke (HR = 0.67, 95% CI = 0.30-1.50) alone, but it was associated with a significant 32% (95% CI = 1-53%) reduction in major bleeding risk compared with warfarin.. Among patients with nonvalvular atrial fibrillation and stage 4 or 5 chronic kidney disease or undergoing hemodialysis, rivaroxaban appears associated with significantly less major bleeding compared to warfarin.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin; Young Adult

Older adult patients are underrepresented in clinical trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin.. Retrospective observational study.. The Centers for Medicare & Medicaid Services and three US commercial claims databases.. A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015.. In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB.. The patients in the six matched cohorts had a mean follow-up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49-.69), dabigatran (HR = .77; 95% CI = .60-.99), and rivaroxaban (HR = .74; 95% CI = .65-.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54-.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78-1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07-1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47-.89; MB: HR = .60; 95% CI = .49-.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59-.86; MB: HR = .50; 95% CI = .45-.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67-.90) compared with rivaroxaban.. Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662-1671, 2019.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Medicare; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

Prescribers' concern regarding falls resulting in intracranial hemorrhage is often cited as a justification for under-utilization of oral anticoagulation. We evaluated the safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. Using MarketScan claims from 11/2012-3/2017, we identified adult, oral anticoagulation-naïve, new-initiators of oral factor Xa inhibitors or warfarin with nonvalvular atrial fibrillation, ≥ 12 months of insurance coverage prior to starting oral anticoagulation and a predicted 2-year risk of falls ≥ 15%. Differences in baseline covariates between cohorts were balanced using inverse probability-of-treatment weights based on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for intracranial hemorrhage and stroke or systemic embolism were estimated. Among 25,144 nonvalvular atrial fibrillation patients at high-risk for falls (observed fall rate = 11.8%/person-year), oral factor Xa inhibitor use was associated with a 43% (95% CI = 5-65%) reduced hazard of intracranial hemorrhage compared to warfarin. Oral factor Xa inhibitors did not significantly reduce the hazard of stroke or systemic embolism versus warfarin (HR = 0.86, 95% CI = 0.66-1.11). Findings for the intracranial hemorrhage and stroke or systemic embolism endpoints were similar when apixaban and rivaroxaban were evaluated separately versus warfarin (p-interaction ≥ 0.64 for all). Oral factor Xa inhibitors reduced patients' risk of intracranial hemorrhage and were at least as effective in preventing stroke or systemic embolism as warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.

Topics: Accidental Falls; Aged; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Stroke; Treatment Outcome; Warfarin

Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively.. To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin.. A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic.. Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment.. Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticoagulants; Attitude to Health; Communication Barriers; Contraception Behavior; Embolism; Family Planning Services; Female; Health Knowledge, Attitudes, Practice; Heart Valve Prosthesis Implantation; Humans; Middle Aged; Patient Education as Topic; Pregnancy; Venous Thrombosis; Warfarin; Young Adult

Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range.. To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events.. In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019.. Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range.. Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models.. A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk.. Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Monitoring; Embolism; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Registries; Stroke; Treatment Outcome; Warfarin

Oral anticoagulants use has increased rapidly, internationally. Here we look at risks and benefits, based on Japanese data, of therapy with low risk non-valvular atrial fibrillation patients.. Using a health insurance claims data set we assessed: (i) oral anticoagulants usage in Japan, and (ii) efficacy and safety of dabigatran compared with warfarin, in Japanese patients with non-valvular atrial fibrillation, aged 18-74 years.. We identified 4380 non-valvular atrial fibrillation patients treated with anticoagulants between 1 January 2005, and 28 February 2014, and estimated the adjusted hazard ratio for stroke or systemic embolism, and any hemorrhagic event (Cox proportional hazards regression model with stabilized inverse probability treatment weighting).. The data included 101 989 anticoagulant prescriptions for 4380 patients, of which direct oral anticoagulants increased to 40.0% of the total by the end of the study. After applying exclusion criteria, 1536 new non-valvular atrial fibrillation patients were identified, including 1071 treated with warfarin and 465 with dabigatran. Mean ages were 56.11 ± 9.70 years for warfarin, and 55.80 ± 9.65 years for dabigatran. The adjusted hazard ratio (95% confidence interval), comparing dabigatran with warfarin, was 0.48 (0.25-0.91) for stroke or systemic embolism, and 0.91 (0.60-1.39) for any hemorrhage including intracranial and gastrointestinal.. Number of patients prescribed direct oral anticoagulants steadily increased, and incidence of all-cause bleeding related to dabigatran was similar to warfarin, in our study population of younger non-valvular atrial fibrillation patients. Dabigatran, compared with warfarin, generally reduced risk of all-cause stroke and systemic embolism.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Drug Prescriptions; Embolism; Female; Hemorrhage; Humans; Incidence; Japan; Logistic Models; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Stroke; Warfarin; Young Adult

To evaluate inpatient oral anticoagulant (OAC) treatment, discharge location, and post-discharge OAC treatment for patients hospitalized with non-valvular atrial fibrillation (NVAF).. Retrospective study using claims data linked to hospital electronic health records (EHR). Patients (n = 2,484) were hospitalized with a primary (38%) or secondary (62%) diagnosis of AF without evidence of mitral valvular heart disease or valve replacement between January 2009 and September 2013. Inpatient OAC treatment was identified from EHR data.. Inpatient and post-discharge OAC treatment [direct OAC (DOAC; apixaban, rivaroxaban, dabigatran), warfarin, no OAC] and discharge location (long-term care, home health-care, home self-care).. Mean age was 72.6 years, 61.2% were male, and 89.5% had a CHA2DS2-VASc score ≥2. Overall, 6.4% received a DOAC, 38.0% warfarin, and 55.6% no OAC during hospitalization. Compared to other treatment groups, patients receiving DOAC were younger and more likely to be male. The majority (72.2%) were discharged to home health-care, 13.2% home self-care, and 6.0% long-term care. Among patients who were treated with warfarin during hospitalization, 40.3% filled a warfarin prescription within 30 days post-discharge, whereas among patients who were treated with a DOAC, 52.4% filled a DOAC prescription within 30 days post-discharge. Some NVAF patients not treated with an OAC during hospitalization filled a prescription for warfarin (18.0%) or DOAC (1.9%) within 30 days post-discharge. Results were similar among patients with CHA2DS2-VASc score ≥2.. Most patients hospitalized for NVAF were discharged to home support, and the majority did not have OAC treatment during hospitalization or the 30 days post-discharge. Additional investigation should be conducted on trends beyond 30 days post-hospitalization, and the reasons for not receiving anticoagulation therapy in patients at moderate-to-severe risk of stroke or systemic embolism. Helping to avoid preventable strokes is an important goal for public health.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Hospitalization; Humans; Inpatients; Male; Middle Aged; Outpatients; Patient Discharge; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

To describe anticoagulation characteristics in patients with cardiac complications from Chagas disease and compare participants with and without cardioembolic ischemic stroke (CIS). A retrospective cohort of patients with Chagas disease, using anticoagulation, conducted from January 2011 to December 2014. Forty-two patients with Chagas disease who were using anticoagulation were studied (age 62.9±12.4 years), 59.5% female and 47.6% with previous CIS, 78.6% with non-valvular atrial fibrillation and 69.7% with dilated cardiomyopathy. Warfarin was used in 78.6% of patients and dabigatran (at different times) in 38%. In the warfarin group, those with CIS had more medical appointments per person-years of follow-up (11.7 vs 7.9), a higher proportion of international normalized ratios within the therapeutic range (57% vs 42% medical appointments, p = 0.025) and an eight times higher frequency of minor bleeding (0.64 vs 0.07 medical appointments). Patients with Chagas disease and previous CIS had better control of INR with a higher frequency of minor bleeding.

Topics: Aged; Anticoagulants; Brain Ischemia; Chagas Cardiomyopathy; Dabigatran; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Stroke; Warfarin

The management of atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs), but data on their clinical effectiveness and safety outside clinical trial settings are limited.. The RAFFINE registry is an observational, multicenter, prospective registry of Japanese patients with AF, designed to follow clinical events over 3 years. Patient enrollment was conducted from 2013 to 2015 at university hospitals, general hospitals, and private clinics to ensure inclusion of a broad spectrum of representative AF patients. The primary outcome events in this study will be ischemic stroke, systemic embolism, and major bleeding.. We enrolled 3901 ambulatory patients with AF from 4 university hospitals and 50 general hospitals/clinics in Japan. The mean patient age was 72.6 years and 68.5% were male. The type of AF was paroxysmal in 37.8%, persistent in 9.3%, and permanent in 51.7%. Major coexisting diseases were hypertension (72.7%), diabetes mellitus (30.3%), congestive heart failure (23.8%), history of ischemic stroke or transient ischemic attack (15.1%), and coronary artery disease (13.7%). Of the entire cohort, 44.6% were treated with warfarin and 43.0% were treated with DOACs. The prescription of DOACs exceeded that of warfarin in the general hospitals and clinics. Risk scores such as CHADS. The RAFFINE registry at baseline described the current status of anticoagulation therapy in Japan and long-term follow-up data will identify how outcomes vary between stratified groups in patients with AF in the DOAC era (UMIN Clinical Trials Registry UMIN000009617).

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Diabetes Complications; Embolism; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Prospective Studies; Registries; Research Design; Risk Factors; Treatment Outcome; Warfarin

In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation.. A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence.. As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs.. Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Topics: Administration, Oral; Age Factors; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Warfarin

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.. Non-valvular atrial fibrillation patients aged ≥65 years diagnosed with coronary/peripheral artery disease in the US Medicare population, newly initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected from January 1, 2013 to September 30, 2015. Propensity score matching was used to compare DOACs vs warfarin. Cox proportional hazards models were used to estimate the risk of stroke/systemic embolism, major bleeding, and composite of stroke/myocardial infarction/all-cause mortality.. There were 15,527 apixaban-warfarin, 6,962 dabigatran-warfarin, and 25,903 rivaroxaban-warfarin-matched pairs, with a mean follow-up of 5-6 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.37-0.62), major bleeding (HR 0.66; 95% CI, 0.58-0.75), and stroke/myocardial infarction/all-cause mortality (HR 0.63; 95% CI, 0.58-0.69); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.79; 95% CI, 0.70-0.90 and HR 0.87; 95% CI, 0.81-0.92, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.72; 95% CI, 0.60-0.89) and a higher rate of major bleeding (HR 1.14; 95% CI, 1.05-1.23) vs warfarin.. All DOACs were associated with lower stroke/myocardial infarction/all-cause mortality rates compared with warfarin; differences were observed in rates of stroke/systemic embolism and major bleeding. Findings from this observational analysis provide important insights about oral anticoagulation therapy among non-valvular atrial fibrillation patients with coronary/peripheral artery disease and may help physicians in the decision-making process when treating this high-risk group of patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Medicare; Myocardial Infarction; Peripheral Arterial Disease; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

Women with atrial fibrillation are at a higher risk of stroke, despite treatment with warfarin. It is unclear if women treated with direct oral anticoagulants (DOACs) have better clinical outcomes, especially when considering the quality of anticoagulation control of warfarin.. This study compared the effectiveness and safety outcomes of DOACs versus warfarin in men and women with stratifications for anticoagulation control.. Patients newly diagnosed with atrial fibrillation and prescribed oral anticoagulants during 2010 to 2015 were identified using the Hong Kong clinical database. Propensity score matching was performed in men and women separately. Further analysis was conducted to stratify warfarin users according to their anticoagulation control. Cox regression was used to compare the risk of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding, and all-cause mortality in the specific sex.. There were 4,972 men and 4,834 women successfully matched in our cohort. Compared with warfarin, DOAC use was associated with a lower risk of ICH (hazard ratio [HR]: 0.16; 95% confidence interval [CI]: 0.06 to 0.40) and all-cause mortality (HR: 0.55; 95% CI: 0.39 to 0.77) in women but not in men. The treatment by sex interaction was significant for ICH only, and a significantly lower risk of ICH remained in the DOAC group when compared with warfarin users with good anticoagulation control (HR: 0.13; 95% CI: 0.02 to 1.00) among women only. The risks of ischemic stroke or systemic embolism and gastrointestinal bleeding with DOACs versus warfarin were comparable in both sexes.. DOACs were associated with a lower risk of ICH and all-cause mortality in women only, where the association of lower ICH risk remained when compared with warfarin users with good anticoagulation control.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Embolism; Female; Hemorrhage; Hong Kong; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Sex Factors; Stroke; Treatment Outcome; Warfarin

Although direct oral anticoagulants (DOACs) are widely used in Japanese patients with atrial fibrillation (AF), large-scale investigations into their use, with suitable follow-up times and rates, are lacking. Methods and Results: The SAKURA AF Registry is a prospective multicenter registry created to investigate therapeutic outcomes of oral anticoagulant (OAC) use in Japanese AF patients. We conducted a study involving 3,237 enrollees from 63 institutions in the Tokyo area being treated with any of 4 DOACs (n=1,676) or warfarin (n=1,561) and followed-up for a median of 39.3 months (range 28.5-43.6 months). Analyses of 1- and 2-year follow-up data available for 3,157 (97.5%) and 2,952 (91.2%) patients, respectively, showed no significant differences in rates of stroke or systemic embolism (SE), major bleeding, and all-cause mortality for DOAC vs. warfarin users (1.2 vs. 1.8%/year, 0.5 vs. 1.2%/year, and 2.1 vs. 1.7%/year, respectively). Under propensity score matching, the incidence of stroke or SE (P=0.679) and all-cause death (P=0.864) remained equivalent, but the incidence of major bleeding was significantly lower (P=0.014) among DOAC than warfarin users.. A high follow-up rate allowed us to obtain reliable data on the status of OAC use and therapeutic outcomes among AF patients in Japan. Warfarin and DOACs appear to yield equivalent 3-year stroke and all-cause mortality rates, but DOACs appear to reduce the risk of major bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Japan; Male; Middle Aged; Mortality; Propensity Score; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Advances in cancer therapy have led to a significant improvement of survival in most types of malignancies over the past few decades. As a result, there is a growing population of cancer survivors, expected to reach 18 million people in 2030 in the US and a similar number in Europe. Interestingly, cancer survivor studies have shown that although about half of these patients eventually die of cancer, one third of them actually die of cardiovascular disease. Arrhythmias represent a significant part of cardiovascular complications and atrial fibrillation is the main arrhythmia occurring in cancer patients.Antithrombotic therapy is a challenge: the optimal international normalized ratio (INR) level in patients on therapy with vitamin K antagonists is achieved in only 12% of them; in these patients, direct oral anticoagulants seem to be effective and safe for the prevention of stroke and systemic embolic events compared to warfarin and have similar risk of major bleeding. Among the trials, ENGAGE AF-TIMI 48 provides more data on the efficacy and safety of edoxaban in cancer patients.

Topics: Anticoagulants; Atrial Fibrillation; Cancer Survivors; Cardiovascular Diseases; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; International Normalized Ratio; Neoplasms; Pyridines; Stroke; Thiazoles; Warfarin

Background and Purpose- Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods- In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results- The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels ( P for interaction=0.023). Conclusions- In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyridines; Stroke; Thiazoles; Warfarin

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF - TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230-771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78-3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07-2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83-1.42). Relative outcomes with higher-dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31-1.15] for malignancy versus HR , 0.89 [95% CI, 0.76-1.05] for no malignancy; interaction P=0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69-1.40] for malignancy versus HR , 0.79 [95% CI, 0.69-1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher-dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31-0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88-1.18; interaction P=0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Gastrointestinal Neoplasms; Hemorrhage; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prostatic Neoplasms; Pyridines; Stroke; Thiazoles; Warfarin

Background There is concern that selective serotonin reuptake inhibitors ( SSRI s) substantially increase bleeding risk in patients taking anticoagulants. Methods and Results We studied 737 patients taking SSRI s in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Embolism and Stroke Trial in Atrial Fibrillation) trial of rivaroxaban compared with warfarin for the prevention of stroke/systemic embolism in patients with atrial fibrillation. These patients were propensity score matched 1:1 to 737 patients not taking SSRI s. The primary outcome measure was major and nonmajor clinically relevant bleeding events, the principal safety outcome in ROCKET AF . Over a mean 1.6 years of follow-up, the rate of major/ nonmajor clinically relevant bleeding was 18.57 events/100 patient-years for SSRI users versus 16.84 events/100 patient-years for matched comparators, adjusted hazard ratio ( aHR ) of 1.16 (95% confidence interval [CI], 0.95-1.43). The aHR s were similar in patients taking rivaroxaban ( aHR 1.11 [95% CI, 0.82-1.51]) and those taking warfarin ( aHR 1.21 [95% CI, 0.91-1.60]). For the rarer outcome of major bleeding, the aHR for SSRI users versus those not taking SSRI s was 1.13 (95% CI, 0.62-2.06) for rivaroxaban; for warfarin, the aHR was higher, at 1.58 (95% CI , 0.96-2.60) but not statistically significantly elevated. Conclusions We found no significant increase in bleeding risk when SSRI s were combined with anticoagulant therapy, although there was a suggestion of increased bleeding risk with SSRI s added to warfarin. While physicians should be vigilant regarding bleeding risk, our results provide reassurance that SSRI s can be safely added to anticoagulants in patients with atrial fibrillation . Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00403767.

Topics: Aged; Anticoagulants; Anxiety Disorders; Atrial Fibrillation; Depressive Disorder; Embolism; Female; Hemorrhage; Humans; Male; Proportional Hazards Models; Risk Factors; Rivaroxaban; Selective Serotonin Reuptake Inhibitors; Stroke; Warfarin

To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.. Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.. Of the 186,132 eligible patients, 20,803 apixaban-warfarin pairs, 52,476 rivaroxaban-warfarin pairs, and 16,731 dabigatran-warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.. Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Costs and Cost Analysis; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Medicare; Proportional Hazards Models; Pyrazoles; Pyridones; Risk; Rivaroxaban; Stroke; United States; Warfarin

An 80-year-old woman had an aortic valve replacement 1 month before admission and took warfarin for transient atrial fibrillation. She developed a disturbance of consciousness and left hemiplegia. On admission, the right radial artery was slightly palpable. Head MRI images showed a hyper-intense area in the right middle cerebral artery territory. MRA images showed an occlusion of the right M1 distal site and decreased signal at the right internal carotid artery. Contrast CT images of the ascending aorta showed an embolus in the innominate artery. She was diagnosed with an innominate artery saddle embolus and occlusion of the right cerebral artery due to cardiac embolism. She was treated with a heparin infusion and warfarin. She recovered consciousness and from hemiplegia gradually. Recanalization of the innominate artery and right cerebral artery was confirmed. In cases where the radial artery is slightly palpable, it is necessary to consider an innominate artery saddle embolus in addition to aortic dissection.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brachiocephalic Trunk; Cerebral Infarction; Drug Therapy, Combination; Embolism; Female; Heparin; Humans; Infarction, Middle Cerebral Artery; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Treatment Outcome; Warfarin

No studies have performed direct pairwise comparisons of the effectiveness and safety of warfarin and the new oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban. Using 2013 to 2014 claims from a 5% random sample of Medicare beneficiaries, we identified patients newly diagnosed with atrial fibrillation who initiated apixaban, dabigatran, rivaroxaban, warfarin, or no oral anticoagulation therapy in 2013 to 2014. Outcomes included the composite of ischemic stroke, systemic embolism (SE) and death, any bleeding event, gastrointestinal bleeding, intracranial bleeding, and treatment persistence. We constructed Cox proportional hazard models to compare outcomes between each pair of treatment groups. The composite risk of ischemic stroke, SE, and death was lower for NOACs than for warfarin: hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76 to 0.98 for apixaban; 0.73, 95% CI 0.63 to 0.86 for dabigatran; and 0.82, 95% CI 0.75 to 0.89 for rivaroxaban, all compared with warfarin. There were no differences in effectiveness across NOACs. The risk of any bleeding was lower with apixaban than with warfarin, but higher with rivaroxaban than with warfarin. Apixaban (HR 0.69, 95% CI 0.60 to 0.79) and dabigatran (HR 0.79, 95% CI 0.69 to 0.92) were associated with lower bleeding risk than rivaroxaban. Treatment persistence was highest for apixaban (82%), and lowest for dabigatran and warfarin (64%) (p value <0.001). Compared with warfarin, NOACs are more effective in preventing stroke but their risk of bleeding varies, with rivaroxaban having higher risk than warfarin. Altogether, apixaban had the most favorable effectiveness, safety, and persistence profile.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Male; Pennsylvania; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Prevalence of atrial fibrillation (AF) is increasing, due partly to the ageing population. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) Trial, published in 2007, provided strong evidence of the effectiveness of warfarin at age≥80 years, but the impact on incidence of AF-related stroke and peripheral embolic vascular events is uncertain.. We studied age-specific incidence and outcome of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study.. Of 3096 acute cerebral or peripheral vascular events, 748 (24.2%) were AF-related. Of the 597 disabling/fatal incident ischaemic strokes, 369 occurred at age ≥80 years, of which 124 (33.6%) were in non-anticoagulated patients with known prior AF. There was no reduction in incident AF-related events after 2007 at all ages (n=231 vs 211; adjusted RR=1.11, 0.91 to 1.36, p=0.29) or at age ≥80 (137 vs 135, RR=1.15, 0.94 to 1.40, p=0.17). Scope for improved prevention at older ages was considerable. Among 208 patients with incident AF-related events at age ≥80 and known prior AF, only 19 (9.1%) were anticoagulated. Of the 189 patients not anticoagulated, 166 (87.8%) had no major disability prior to the event and 167 (88·4%) had a high embolism risk score, of whom 139 (83.2%) were also at low risk of complications. Yet, 125/167 (74.9%) were dead or institutionalised after the event. Potentially preventable embolic events outnumbered warfarin-related intracerebral haemorrhages by about 15-fold (280 vs 19), rising to 50-fold (189 vs 4) at age ≥80 years.. We found no reduction in incidence of AF-related vascular events since publication of the BAFTA trial. A third of all disabling/fatal strokes occur in non-anticoagulated patients with known prior AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; England; Female; Humans; Incidence; Male; Stroke; Time Factors; Treatment Outcome; Warfarin

Few data exist to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) undergoing cryoballoon ablation (CB-A). This study is aimed to clarify the usefulness of DOACs in patients undergoing CB-A.. The patients (average age; 65.8±11.9 years old, male 69%) were stratified into one of five subsets based on the type of anticoagulation (warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban), and underwent CB-A. A brain MRI was performed in all patients the day after the CB-A for AF. A total of 257 (19 on warfarin, 30 on apixaban, 66 on dabigatran, 81 on rivaroxaban, and 61 on edoxaban) patients met the inclusion criteria.. The incidence of silent cerebral ischemic lesion was 1 (11.1%) patients on warfarin, 5 (33.3%) on apixaban, 8 (27.6%) on dabigatran, 10 (21.3%) on rivaroxaban, and 10 (29.4%) on edoxaban (p=0.17). Major ischemic events occurred in one patient (1.6%) on edoxaban and one (5.3%) on warfarin. Minor bleeding complications occurred in 1 patient (5.3%) on warfarin, 2 (6.7%) on apixaban, 1 (1.2%) on rivaroxaban, 5 (7.6%) on dabigatran, and 2 (3.3%) on edoxaban (p=0.24). Of note, major bleeding complications occurred in 2 patients (3.3%) on apixaban, 1 (1.2%) on rivaroxaban, 1 (1.5%) on dabigatran, 1 (1.6%) on edoxaban, and 2 (10.5%) on warfarin (p<0.05).. Warfarin use significantly increased the risk of serious bleeding, in contrast, CB-A did not place the patients at an increased risk of complications under a DOAC treatment. There were no significant differences regarding preventing embolic events among the DOAC drugs.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain; Brain Ischemia; Cryosurgery; Dabigatran; Embolism; Female; Hemorrhage; Humans; Incidence; Magnetic Resonance Imaging; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Gastrointestinal Hemorrhage; Humans; Neoplasms; Stroke; Warfarin

We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD.. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P=0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03).. Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Proportional Hazards Models; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Creatinine; Embolism; Factor Xa Inhibitors; Humans; Kidney; Kidney Function Tests; Rivaroxaban; Stroke; Vitamin K; Warfarin

Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes.. We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality.. Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS. Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia.

Topics: Aged; Aged, 80 and over; Anemia; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Mortality; Multivariate Analysis; Proportional Hazards Models; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Warfarin

Atrial fibrillation (AF) is the commonest cardiac arrhythmia including in end-stage renal failure patients, but controversy remains whether these patients benefit from anticoagulation. We reviewed the characteristics, management and outcomes of end-stage renal failure patients on dialysis with AF.. All patients started on dialysis at Middlemore Hospital between January 2000 and December 2008 who had AF were studied. Data regarding demographics, co-morbidities, renal disease, AF and embolic, bleeding and/or mortality events were recorded.. There were 141 out of 774(18.2%) dialysis patients with AF followed-up for 4.4+/-2.5 years, and 41.8%(59) were on warfarin. Incidence of all embolic events, ischaemic stroke, all bleeding and intracranial bleed were 4.1, 3.1, 9.6 and 0.82/100 person years respectively. Warfarin anticoagulation was associated with increased risk of intracranial bleed (hazards ratio=11.1, P=0.038), but not total embolic, bleeding events or mortality during follow-up (P=0.317-0.980). All three scores (CHADS2, CHA2DS2-VASc and HAS-BLED) could detect all embolic events (c=0.808-0.838), but not bleeding events (c=0.459-0.498).. Anticoagulation with warfarin didn't significantly reduce embolism or mortality in dialysis patients with AF, but increased the risk of intracranial bleeds. Convention risk scores predict embolic but not bleeding events in these patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Risk Factors; Warfarin

Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear.. We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups.. In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; Warfarin

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

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Drug Approval; Embolism; Europe; Evidence-Based Medicine; Factor Xa Inhibitors; Humans; International Normalized Ratio; Rivaroxaban; Stroke; United States; United States Food and Drug Administration; Warfarin

A 57-year-old woman with known moderate-to-severe mitral stenosis and atrial fibrillation (AF) presented to the emergency department with acute onset right loin pain after having a coronary angiogram and left and right heart catheterisation through the right femoral route about 28 h ago. The cardiac catheterisation was done after she presented with one episode of troponin-negative chest pain and progressive shortness of breath. She had anterior wall myocardial infarction (MI) 25 years ago, which was thought to be due to coronary artery embolism. Her mitral stenosis was diagnosed at that stage.Her warfarin was stopped for 5 days before cardiac catheterisation and international normalised ratio (INR) on the day of the procedure was 1.1. No bridging heparin/low molecular weight heparin (LMWH) was used and warfarin was restarted on the evening of the procedure at the usual dose. Clinical examination revealed some guarding in the right iliac fossa and some tenderness in the right loin. She was not feverish and there was no dysuria or frequency. There was no lump at the puncture site.On presentation to the emergency department, a contrast-enhanced CT scan of the abdomen was performed (figures 1 and 2).. Which of the following is the aetiology of the pain? Abdominal aortic dissectionRenal artery embolismRetroperitoneal haematomaUreteric stone.

Topics: Administration, Intravenous; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Coronary Angiography; Drug Administration Schedule; Embolism; Female; Flank Pain; Heparin; Humans; International Normalized Ratio; Middle Aged; Mitral Valve Stenosis; Renal Artery Obstruction; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Female patients have higher risk for stroke than male patients in nonanticoagulated atrial fibrillation patients, but limited data are available on sex differences in stroke and bleeding outcomes among patients with anticoagulated atrial fibrillation on warfarin, especially in relation to quality of anticoagulation control, as reflected by the time in therapeutic range (TTR).. We investigated adverse outcomes in females (n=791) and males (n=1501) among 2292 patients with atrial fibrillation taking warfarin arm in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial.. The combined end point of cardiovascular death and stroke/systemic embolism (SSE) was similar in females versus males. There was no sex differences in either cardiovascular death or SSE. Compared with males, females had a lower risk of major bleeding (hazard ratio, 0.39; 95% confidence interval, 0.18-0.87; P=0.02). No differences were seen in mortality and stroke outcomes between females and males either in the prespecified age subgroups or in relation to TTR categories. TTR was negatively correlated with any clinically relevant bleeding in both females (r=-0.86; P=0.03) and males (r=-0.94; P=0.005). On Cox regression, TTR (but not female sex) emerged as an independent predictor for combined cardiovascular death/SSE and clinically relevant bleeding events.. Anticoagulated female patients with atrial fibrillation had a similar rate of cardiovascular death and SSE, but a lower risk of major bleeding, compared with males. TTR (but not female sex) was an independent predictor for combined cardiovascular death and SSE and clinically relevant bleeding events.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Sex Factors; Stroke; Warfarin

Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation (AF).. We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation (OAC; warfarin or novel oral anticoagulants [NOAC]). Secondary outcomes of interest included the proportion of patients prescribed NOACs (dabigatran or rivaroxaban); time in therapeutic range (TTR) for warfarin users, all-cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P=0.079), but less likely to receive NOAC at baseline or follow-up (12.1% vs 16.3%; unadjusted P=0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [OR]=0.68; 95% CI=0.49, 0.94), but was not associated with OAC use overall (OR=0.82; 95% CI=0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P<0.0001; adjusted TTR difference, -2.9; 95% CI=-5.7, -0.2; P=0.04). Use of an NOAC over 2 years of follow-up was not statistically different by insurance. Compared with non-Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics.. In a contemporary AF cohort, use of OAC overall and use of NOACs were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Dabigatran; DNA-Binding Proteins; Drosophila Proteins; Embolism; Female; Hemorrhage; Humans; Male; Medicaid; Middle Aged; Mortality; Registries; Rivaroxaban; Stroke; Transcription Factors; Treatment Outcome; United States; Warfarin

 To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation..  Observational nationwide cohort study..  Three Danish nationwide databases, August 2011 to October 2015..  61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%)..  Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding..  When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5.3%)..  All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting. No significant difference was found between NOACs and warfarin for ischaemic stroke. The risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Denmark; Drug Administration Schedule; Embolism; Female; Hemorrhage; Humans; Male; Propensity Score; Pyrazoles; Pyridones; Registries; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Yes. Dabigatran, rivaroxaban, and apixaban are safe and effective compared with warfarin for preventing stroke in patients with nonvalvular atrial fibrillation. These novel oral anticoagulants (NOACs) are noninferior in reducing the number of strokes and systemic emboli and in lowering all-cause mortality while not increasing major bleeding complications and hemorrhagic events.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Male; Patient Safety; Randomized Controlled Trials as Topic; Stroke; Warfarin

We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF).. The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP.. In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10-mm Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03-1.95) (P = .06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P interaction = .69).. In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin were consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Pressure; Embolism; Female; Hemorrhage; Humans; Hypertension; Male; Middle Aged; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk; Rivaroxaban; Stroke; Warfarin

We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in 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), in particular, those with known coronary artery disease (CAD).. Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors.. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009).. Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Comorbidity; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Warfarin

Anticoagulants are arguably the most important drug family of all, based on the frequency and duration of their use, and the clinical importance and frequency of benefits and harms. Several direct acting oral anticoagulants (DOACs) have recently joined warfarin for the treatment of atrial fibrillation, with a resultant significant expansion in use of oral anticoagulants (OACs). Our objectives are to compare safety and effectiveness of DOACs versus warfarin in a full population where anticoagulation management is good and to identify which types of patients do better with DOACs versus warfarin and vice versa.. This is a retrospective cohort study of all adults living in British Columbia who have a diagnosis of atrial fibrillation in hospital or medical service data, and a first prescription for an OAC. Coprimary outcomes are ischaemic stroke and systemic embolism (benefit) and major bleeding (harm). Secondary outcomes include net clinical benefit (composite of stroke, systemic embolism, major bleeds, myocardial infarction, pulmonary embolism and death), drug discontinuation and individual composite item occurrence. We will estimate the effects of treatment in a 2-year follow-up period, using time-to-event models with propensity score adjustment to control confounding. Secondary analyses will examine 'as treated' outcomes.. The protocol, data creation plan, privacy impact statement and data sharing agreements have been approved. Dissemination is planned via conferences and publications as well as directly to drug policy leaders. Information on the overall comparative effectiveness and safety of DOACs versus warfarin in a country with high quality anticoagulation management, as well as for vulnerable subgroups, will be an important addition to the literature.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; British Columbia; Databases, Factual; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Propensity Score; Retrospective Studies; Stroke; Treatment Outcome; Warfarin; Young Adult

To maximize protection against stroke with minimal bleeding, warfarin therapy in nonvalvular atrial fibrillation (NVAF) requires tight control within a narrow therapeutic range, which might depend on racial variations.. The J-RHYTHM Registry followed 6404 NVAF patients treated with warfarin for 2 years. Using international normalized ratios (INRs) at or closest to the embolic and intracranial hemorrhagic (ICH) events, we determined odds ratios for ischemic stroke/systemic embolism (SE) and ICH according to any given INR with a reference INR range including 2.0.. Ischemic stroke and SE occurred in 97 of the patients and ICH occurred in 49. The estimated INR-risk relationships showed characteristics of Japanese NVAF patients. Compared to INR-risk relationships reported for Westerners, those observed in Japanese patients were virtually identical for ischemic stroke/SE and shifted leftward by approximately 0.5 INR for ICH.. This is the largest Japanese study providing fundamental data necessary to establish optimal anticoagulation intensities. Japanese NVAF patients may require narrower therapeutic ranges than Westerners.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Japan; Male; Middle Aged; Odds Ratio; Registries; Risk; Stroke; Warfarin

The risk of ischemic stroke/thromboembolic events after an intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) who are on warfarin treatment is poorly characterized. The aim of this study was to assess the association between the risk of ischemic stroke/thromboembolic events and ICH.. Linkage of three Danish nationwide administrative registries in the period between 1999 and 2012 identified patients with AF on warfarin treatment. Event-rate ratios of stroke/thromboembolic events, major bleeding, and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched OR was calculated for ICH occurrences within 0 to 3 months relative to the 3 to 6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.. We studied 58,815 patients with AF (median age, 72.6 years; 60% men). When compared with the non-ICH group, the ICH group was at increased risk for stroke/systemic embolism/transient ischemic attack (TIA) (rate ratio, 3.67; 95% CI, 3.12-4.31) and mortality (rate ratio, 5.55; 95% CI, 5.20-5.92), but not for major bleeding (rate ratio, 1.06; 95% CI, 0.81-1.39). The matched OR of ICH occurrences prior to a stroke/systemic embolism/TIA was 4.33 (95% CI, 2.44-8.15). The rate ratio of claimed warfarin prescriptions post- and pre-ICH event was 0.28 (95% CI, 0.24-0.33).. In this large-scale study of patients with AF treated with warfarin, first-time ICH was associated with an increased rate of ischemic stroke/systemic embolism/TIA and mortality compared with the non-ICH group. There was a decrease in the warfarin-prescription purchase rate in the post-ICH period compared with pre-ICH, which may partly explain the excess risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Denmark; Embolism; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Prevalence; Registries; Retrospective Studies; Risk Factors; Stroke; Survival Rate; Warfarin

Management of non-valvular atrial fibrillation (NVAF) focuses on the use of anticoagulation to mitigate the risk of stroke. Until recently, vitamin K antagonist (VKA) treatment was considered the standard of care, with the emergence of non-VKA oral anticoagulants (NOACs) shifting treatment practice. The objective of this study was therefore to assess the use of warfarin and the NOACs for stroke prevention in patients with NVAF from the perspective of a Belgian healthcare payer using a cost-effectiveness analysis and the efficiency frontier approach.. A previously published Markov model was adapted to the Belgian healthcare setting. Clinical events modelled include ischaemic and haemorrhagic stroke, systemic embolism, intracranial haemorrhage, other major bleeding, clinically relevant non-major bleeding, myocardial infarction, cardiovascular hospitalisation and treatment discontinuations. Efficacy and bleeding data for warfarin and apixaban 5 mg twice daily were obtained from the ARISTOTLE trial, whilst those for other NOACs (rivaroxaban 20 mg once daily, dabigatran 110 mg twice daily, dabigatran 150 mg twice daily) were from published indirect comparisons. Acute medical costs were obtained from reimbursement payments made to Belgian hospitals, whilst long-term medical costs and utility data were derived from the literature. The efficiency frontier was calculated using total costs and quality-adjusted life-years (QALYs) as outcomes. Univariate and probabilistic sensitivity analyses were performed.. Warfarin and apixaban were the two optimal treatment choices, as the other three treatment alternatives including dabigatran 110 mg, dabigatran 150 mg switching to dabigatran 110 mg at the age of 80 years and rivaroxaban were extendedly or strictly dominated on the efficiency frontier. Apixaban was a cost-effective alternative vs warfarin at an incremental cost-effectiveness ratio of 7,212/QALY gained.. Amongst NOACs, apixaban may be the most economically efficient alternative to warfarin in NVAF patients who are suitable for VKA treatment and eligible for stroke prevention in Belgium.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Belgium; Cohort Studies; Embolism; Humans; Markov Chains; Quality-Adjusted Life Years; Stroke; Warfarin

Caseous mitral annulus calcification involving aortomitral curtain is a rare occurrence. We report a case of a 64-year-old woman with end-stage renal failure and a candidate for renal transplant who presented with late ST-elevation myocardial infarction. Intracoronary imaging, computed tomography cardiac imaging, and histopathology confirmed coronary embolus into the left main stem artery from an extensive caseous mitral annulus calcification.

Topics: Anticoagulants; Coronary Angiography; Coronary Vessels; Embolism; Female; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Mitral Valve; Multimodal Imaging; Myocardial Infarction; Predictive Value of Tests; Risk Assessment; Sensitivity and Specificity; Tomography, Spiral Computed; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Interventional; Vascular Calcification; Warfarin

Topics: Anticoagulants; Coronary Artery Disease; Dyspnea; Echocardiography, Transesophageal; Embolism; Foramen Ovale, Patent; Humans; Intracranial Embolism; Magnetic Resonance Angiography; Male; Middle Aged; Multimodal Imaging; Pulmonary Embolism; Renal Artery Obstruction; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Embolism; Female; Humans; Male; Prosthesis Implantation; Stroke; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Embolism; Female; Humans; Male; Prosthesis Implantation; Stroke; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Embolism; Female; Humans; Male; Prosthesis Implantation; Stroke; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Embolism; Female; Humans; Male; Prosthesis Implantation; Stroke; Warfarin

This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention.. We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives.. Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention.. Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient's condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Decision Support Techniques; Embolism; Evidence-Based Medicine; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Rivaroxaban; Stroke; Warfarin

Topics: Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Embolism; Humans; Pyridines; Recurrence; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Atrial fibrillation is the most common arrhythmia and is associated with significant morbidity and mortality. The current therapeutic options for patients at high thromboembolic risk include the vitamin K antagonists and the direct oral anticoagulants. These novel agents have been evaluated in more than 40,000 patients enrolled in four large randomized controlled trials for stroke prevention in non-valvular atrial fibrillation. When these results were pooled together, a greater efficacy profile, as well as a consistent reduction in life-threatening bleeding was shown in comparison to vitamin K antagonists. Randomized controlled trials offer the highest level of evidence on the efficacy and safety of an intervention; however, their results may not be directly applicable to the general population. The results of a number of post-marketing observational studies from the United States and Europe have been published. The results of these studies substantially confirm the findings of the randomized trials and show a favorable safety profile with the use of the direct oral anticoagulants even in unselected populations.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Europe; Female; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; United States; 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

Direct oral anticoagulants (DOAC) represent an innovative and relevant treatment for the prevention of cardiac embolism in patients with atrial fibrillation (AF). Their introduction has been followed by an ample debate on their appropriate use, considering that they can offer an effective treatment for the many patients with AF, which are not taking any effective anticoagulant treatment, even though they have a substantial thromboembolic risk (1). On the other hand, DOAC are much less tested in everyday clinical practice and much more expensive than anti-vitamin k anticoagulants (AVKs). Starting from the quite favorable results of the available randomized controlled trials (RCTs)--showing that DOAC are at least non-inferior to AVK and that may be even better for some outcomes--this article discusses their transferability to the majority of AF patients. In summary, the body of evidence supports the efficacy and safety of DOAC in patients carrying demographic and clinical characteristics similar to subjects included in RCT, but their use in less well-characterized subpopulations requires particular caution, while waiting for more reliable data from the real world.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Humans; Male; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

In this study, we evaluated the microembolic signals (MES) frequency with transcranial Doppler ultrasound (TCD) in patients with atrial fibrillation (AF) under anticoagulant therapy, and we compared the treatment groups.. Ninety-nine patients with nonvalvular AF with a history of stroke using warfarin (46%), 67 patients using rivaroxaban (31%), and 49 patients using dabigatran (23%), that is, a total of 215 patients, who have been referred to the stroke outpatient section of our department from May 2013 to November 2014, were included in the study. CHA(2)DS(2)VASc scoring was made for all patients, and International Normalized Ratio (INR) value was evaluated in patients using warfarin. All patients were monitored with TCD on the middle cerebral arteries bilaterally for 30 minutes. Embolic signals were evaluated according to their density and the mean number of signals in 2 consecutive recordings.. The incidence of emboli in the treatment group was 32 (32%) for warfarin, 24 (36%) for rivaroxaban, and 17 (35%) for dabigatran. The analysis of variance revealed that there was no statistically significant differences between the treatment groups in terms of patients' age (P = .145), CHA(2)DS(2)VASc scores (P = .968), and the number of emboli (P = .783). As CHA(2)DS(2)VASc score increases, number of emboli increase. A statistically significant negative correlation between the number of emboli and INR scores was found in the warfarin group. The number of emboli decreases as INR decreases.. As we aim to reduce the risk of emboli to a minimum with anticoagulant therapy, this screening for MES can give us an idea for the risk of stroke.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Female; Humans; Male; Middle Aged; Middle Cerebral Artery; Rivaroxaban; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Warfarin

Three new oral anticoagulants (NOACs) are currently approved for stroke prevention and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). The objective of this analysis was to assess the cost effectiveness of apixaban against other NOACs for the prevention of stroke in patients with NVAF in Greece.. A Markov model that evaluated clinical events, quality-adjusted life expectancy, and costs for patients treated with apixaban or other NOACs formed the basis of the analysis. Clinical events were modeled for a lifetime horizon, based on clinical efficacy data from an indirect comparison, using the ARISTOTLE, ROCKET-AF, and RE-LY clinical trials. Resource use associated with patient monitoring was elicited via a panel of experts (cardiologists and internists). Cost calculations reflect the local clinical setting and followed a third-party payer perspective (Euros, discounted at 3 %).. Apixaban was projected to reduce the occurrence of clinical events and increase quality-adjusted life expectancy and incremental costs of treatment compared with other NOACs. Taking into account costs of medications, patient monitoring, and management of events, the incremental cost-effectiveness ratios for apixaban 5 mg twice daily vs. dabigatran 110 mg twice daily, dabigatran 150 mg twice daily, and rivaroxaban 20 mg once daily were estimated at €9907/quality-adjusted life-year (QALY), €13,727/QALY, and €6936/QALY gained, respectively. Extensive sensitivity analyses indicated that results were robust over a wide range of inputs.. Based on the results of this analysis, apixaban can be a cost-effective alternative to other NOACs for the prevention of stroke in patients with NVAF in Greece.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Embolism; Greece; Health Care Costs; Humans; Middle Aged; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; Stroke; Warfarin

The RE-LY study demonstrated the safety and efficacy of dabigatran relative to warfarin for stroke prevention in non-valvular atrial fibrillation. It is important to further evaluate safety and effectiveness of drugs in routine care. This study used a sequential cohort design with propensity score matching to compare dabigatran with warfarin among patients in two commercial health insurance databases. New users of these anticoagulants were followed from initiation until discontinuation, the end of the study, or the occurrence of a study outcome (primary study outcomes were stroke and major bleeding). Proportional hazards regression was conducted separately within each data source and results were pooled. Among 19,189 matched dabigatran and warfarin initiators (mean age: 68 years, 36 % female), as-treated follow-up (average of 5 months for dabigatran, 4 months for warfarin) identified 62 and 69 strokes, respectively (pooled HR = 0.77; 95 % CI = 0.54 to 1.09), and 354 and 395 major haemorrhages, respectively (HR = 0.75; 0.65 to 0.87). No meaningful heterogeneity was identified across subgroups, but numeric trends suggest more pronounced stroke prevention by dabigatran relative to warfarin among patients age 75+ (HR = 0.57; 0.33 to 0.97) or with < 6 months of use (HR = 0.51; 0.19 to 1.42). Major bleeds were reduced more by dabigatran among patients aged < 55 (HR = 0.51; 0.30 to 0.87) and with CHADS2 < 2 (HR = 0.58; 0.44 to 0.77). In conclusion, in routine care of patients with non-valvular atrial fibrillation, dabigatran treatment resulted in improved health outcomes compared with warfarin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; Comorbidity; Dabigatran; Databases, Factual; Drug Evaluation; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Hospitalization; Humans; Insurance Coverage; Male; Middle Aged; Myocardial Infarction; Polypharmacy; Propensity Score; Retrospective Studies; Stroke; Thrombophilia; Treatment Outcome; Warfarin; Young Adult

Pradaxa (dabigatran) is a direct thrombin inhibitor approved for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. We describe a case of esophageal ulceration associated with Pradaxa administration in a 75-year-old man. The patient reported difficulty swallowing and a burning sensation after taking his first dose of Pradaxa. An esophagogastroduodenoscopy (EGD) revealed linear ulcerations in the mid-esophagus. Pradaxa was held beginning the day before the EGD. The patient reported that his pain and difficulty swallowing resolved on stopping Pradaxa. Pradaxa is formulated with a tartaric acid excipient to reduce variability in absorption. We hypothesise that the capsule lodged in the patient's esophagus and the tartaric acid may have caused local damage resulting in an esophageal ulcer. It is important to educate patients on proper administration of Pradaxa, to decrease the risk of this rare, but potentially serious adverse event.

Topics: Aged; Anticoagulants; Dabigatran; Embolism; Endoscopy, Gastrointestinal; Esophageal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Male; Stomach; Ulcer; Warfarin

The prevalence of atrial fibrillation increases with age, but age-specific data on the incidence of stroke and death in anticoagulated patients with atrial fibrillation are more limited, particularly with regard to comparisons of relative risks of clinical outcomes between the different age strata in relation to quality of anticoagulation control among warfarin users.. We investigated the incidence of adverse outcomes between tertiles of age groups (age, <67 [n=722]; age, 67-74 [n=747]; and age, ≥75 [n=824]) in 2293 patients with atrial fibrillation participating in warfarin arm in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. The average time in therapeutic range was calculated as a measure of anticoagulation control and related to clinical outcomes.. Absolute rates for stroke/systemic embolism (SSE), cardiovascular death, or any clinically relevant bleeding increased with increasing age strata. The combined end point of cardiovascular death and SSE was the highest in the top tertile (adjusted hazard ratio, 2.63; 95% confidence interval, 1.23-5.63) compared with the middle and lowest tertiles (P for trend=0.01). For bleeding, there was no significant difference in relative risks between the age strata (P for trend=0.55 in the warfarin group and in the warfarin group with time in therapeutic range≥60%, P for trend=0.60). The quality of anticoagulation control (time in therapeutic range) significantly correlated with any clinically relevant bleeding (r=-0.91; P<0.001) and cardiovascular death/SSE rates (r=-0.76; P=0.01).. Elderly patients with atrial fibrillation have higher absolute risks of cardiovascular death, SSE, and bleeding, but relative risks of clinically relevant bleeding are not significantly different with increasing age strata. A significant inverse relationship between time in therapeutic range and bleeding and cardiovascular death/SSE emphasizes the importance of good quality anticoagulation control.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Embolism; Female; Hemorrhage; Humans; Intracranial Embolism; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Stroke; Warfarin

We studied whether anticoagulant use and outcomes differed between rural versus urban Canadian non-valvular atrial fibrillation (NVAF) patients prior to the introduction of direct oral anticoagulant drugs.. Retrospective cohort study of 25,284 adult Albertans with NVAF between April 1, 1999 and December 31, 2008.. Compared to urban patients, rural patients were older (p = 0.0009) and had more comorbidities but lower bleeding risk at baseline. In the first year after NVAF diagnosis, urban patients were less likely to be hospitalized (aOR 0.82, 95%CI 0.77-0.89) or have an emergency department visit for any reason (aOR 0.61, 95%CI 0.56-0.66) but warfarin dispensation rates (72.2% vs 71.8% at 365 days, p = 0.98) and clinical outcomes were similar: 7.8% died in both groups, 3.2% rural vs. 2.8% urban had a stroke or systemic embolism (SSE) (aOR 0.92, 95%CI 0.77-1.11), and 6.6% vs. 5.7% (aOR 0.93, 95%CI 0.81-1.06) had a bleed. Baseline SSE risk did not impact warfarin dispensation (73.0% in those with high vs. 72.8% in those with low CHADS2 score, p = 0.85) but patients at higher baseline bleeding risk were less likely to be using warfarin (69.2% high vs. 73.6% low HASBLED score, p<0.0001) in the first 365 days after diagnosis. In warfarin users, bleeding was more frequent (7.5% vs 6.2%, aHR 1.51 [95%CI 1.33-1.72]) but death or SSE was less frequent (7.0% vs 18.1%, aHR 0.60 [0.54-0.66]).. Warfarin use and clinical event rates did not differ between rural and urban NVAF patients in a universal access publically-funded healthcare system.

Topics: Aged; Aged, 80 and over; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Canada; Cohort Studies; Comorbidity; Embolism; Female; Hospitalization; Humans; Male; Odds Ratio; Patient Outcome Assessment; Population Surveillance; Retrospective Studies; Risk; Rural Population; Stroke; Urban Population; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Enoxaparin; Female; Humans; Male; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Pyridines; Randomized Controlled Trials as Topic; Risk; Stroke; Thiazoles; Warfarin

Anticoagulation therapy is essential in atrial fibrillation (AF), and in Japan, less intense control is popular.. To assess the efficacy and safety with a special reference to low intensity warfarin therapy.. In 488 out of 508 patients with non-valvular AF, prothrombin time-international normalized ratio (PT-INR) was kept at 1.6-2.59, and they were followed for 49.5 months: 2098 person-years. The mean age was 73.7±9.9 years and 62% were male. The patients were divided by age: ≥70 years and <70 years, and by the intensity of warfarin therapy: PT-INR at 1.6-1.99 and at 2.0-2.59, respectively. The clinical data and event rates, ischemic stroke and major bleeding, were compared among the subgroups.. Heart failure, previous stroke, and higher CHADS2 score were more often reported in patients ≥70 years while males were involved more often as younger patients. A total of 166 of 339 patients ≥70 years and 69 of 149 patients <70 years belonged to the low intensity group. Ischemic stroke and major bleeding occurred in 1.47%/year and 1.27%/year, respectively but there was no difference between the two age groups and between the two intensities of warfarin therapy. Time in therapeutic range was a predictor for ischemic stroke. A fall of PT-INR to <1.6 was found in 41.9% with ischemic stroke and a rise >2.61 in 40.0% with major bleeding at the time of the events. Blunt trauma and concomitant use of antiplatelets were risks for intracranial hemorrhage in the patients ≥70 years.. The event rates were similar between the low- (1.6-1.99) and high- (2.0-2.59) intensity warfarin therapy groups in aged patients: <70 years and ≥70 years. Time in therapeutic range and a transient fall or rise in PT-INR were risks for clinical events. Blunt head trauma and concomitant use of antiplatelets were risks for intracranial hemorrhage.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Drug Therapy, Combination; Embolism; Female; Follow-Up Studies; Head Injuries, Closed; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Prothrombin Time; Retrospective Studies; Risk; Sex Factors; Stroke; Time Factors; Warfarin

Economic evaluation of dabigatran, a new anti-antithrombotic agent, is done mostly in Western countries. It remains to be seen whether dabigatran will be cost effective in a practice environment where warfarin is significantly underused and the costs of both warfarin and international normalized ration INR monitoring are cheap.. We performed a cost-effectiveness analysis with a Markov model to evaluate the value of dabigatran to prevent stroke and systemic embolism in patients with atrial fibrillation (AF) in Taiwan. Dabigatran was given through sequential dosing, where patients<80 years old received 150 mg of dabigatran twice a day and the dosage was reduced to 110 mgs for patients ≥ 80 years old. Dabigatran was compared with warfarin under two scenarios: the "real-world adjusted-dose warfarin" assuming all AF patients eligible for warfarin were given the medication and maintained at the INR observed in routine clinical practice in Taiwan, and the "real-world prescribing behaviour" similar to the treatment with antithrombotics in real-world practice in Taiwan, where eligible patients could receive warfarin, aspirin, or no treatment.. The percentage of AF patients who received warfarin, aspirin or no treatment in Taiwan was 16%, 62% and 22%, respectively. The event rates of ischemic stroke per 100 patient-years were 4.5, 8.0, and 6.0 for sequential dabigatran, real-world prescribing behaviour and real-world warfarin use, respectively. The incremental cost-effectiveness ratio was $280 US per quality-adjusted-year (QALY) in the real-world prescribing scenario and $10,551 US/QALY in real-word warfarin use.. Dabigatran was highly cost-effective in a clinical practice setting where warfarin has been significantly underused.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Markov Chains; Pyridines; Stroke; Taiwan; Warfarin

Rivaroxaban was shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) in a randomized controlled trial setting.. To assess real-world safety, effectiveness, and persistence associated with rivaroxaban and warfarin in nonvalvular AF patients.. Healthcare claims from Symphony Health Solutions' Patient Transactional Datasets from May 2011 to July 2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin, with ≥2 AF diagnoses (ICD-9-CM: 427.31) and a CHADS2 score ≥1 during the 180 day baseline period were included. Cohorts were matched 1:4 using propensity score methods. Study outcomes were major bleeding, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, composite stroke and systemic embolism, and venous thromboembolism (VTE) events. Cox proportional hazard models were used to compare event and persistence rates.. The matched sample included 3654 rivaroxaban and 14,616 warfarin patients. Matching was adequate, with all standardized differences in patient characteristics <10%. No significant differences were observed for bleeding and composite stroke and systemic embolism outcomes, although rivaroxaban users were associated with significantly fewer VTE events (hazard ratio [HR] = 0.36, 95% confidence interval [CI]: 0.24-0.54, p < 0.0001) compared to warfarin users. Rivaroxaban was also associated with a significantly lower risk of treatment non-persistence (HR = 0.66; 95% CI: 0.60-0.72, p < 0.0001).. Claims data may have contained inaccuracies, and mortality and laboratory data were not available. Confounding may still have been possible even after propensity score matching. Early use pattern of medications may have changed over time.. This analysis suggests that rivaroxaban and warfarin do not differ significantly in real-world rates of composite stroke and systemic embolism and major, intracranial, or GI bleeding. Rivaroxaban, however, was associated with significantly fewer VTE events and significantly better treatment persistence compared with warfarin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comparative Effectiveness Research; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Propensity Score; Proportional Hazards Models; Retrospective Studies; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin; Young Adult

Atrial fibrillation (AF), the most frequent sustained arrhythmia, is associated with an increased risk of thromboembolic events. The risk of stroke depends on risk factors such as age, hypertension, heart failure, and vascular disease. Thus, antithrombotic therapy is a cornerstone in the management of AF. Warfarin is successfully used to reduce thromboembolic events. More recently, direct thrombin (dabigatran) and factor Xa (apixaban, edoxaban, rivaroxaban) inhibitors have been compared to warfarin in large randomized trials. All new substances have been shown to be non-inferior to warfarin concerning thromboembolic events. Severe bleeding, such as fatal and intracranial bleeding, was less frequent with direct oral anticoagulants. Results of the studies and subgroup analyses are discussed. Further trials using direct oral anticoagulants in special populations such as very old and patients with kidney disease are needed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Embolism; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Warfarin

Coronary embolism is an uncommon cause of myocardial infarction. The usual source of a coronary embolus is an intracardiac thrombus or vegetation. Embolisation to the left main coronary artery is an extremely rare event and is usually fatal. We present a case of a 38-year-old woman with embolisation to the left main coronary artery which further embolised distally to the left anterior descending artery leading to a non-ST elevation myocardial infarction. The non-occlusive nature of the left main coronary artery embolus might have led to a favourable prognosis in our patient.

Topics: Adult; Anticoagulants; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Embolism; Female; Humans; Intra-Aortic Balloon Pumping; Myocardial Infarction; Radiography; Thrombectomy; Ultrasonography; Warfarin

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

Topics: Administration, Intravenous; Adult; Anticoagulants; Antihypertensive Agents; Diagnosis, Differential; Echocardiography; Embolism; Heparin; Humans; Hypertension, Malignant; Hypertrophy, Left Ventricular; Lateral Medullary Syndrome; Magnetic Resonance Angiography; Male; Medulla Oblongata; Vertebral Artery; Vertebral Artery Dissection; Warfarin

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

Three new oral anticoagulants (NOACs) have recently become available in the United Kingdom as an alternative to warfarin in the prevention of stroke and systemic embolism in atrial fibrillation. This study examines the relative cost-effectiveness of dabigatran (BID dosing of 150 mg or 110 mg based on patient age), rivaroxaban, and apixaban from a UK payer perspective.. A previously published model that follows up patients through treatment of atrial fibrillation during a lifetime was adapted to allow comparison of the 3 NOACs and warfarin. Acute thromboembolic and bleeding events, as well as long-term consequences of stroke, intracranial hemorrhage, and acute myocardial infarction, were tracked. Relative efficacy was calculated from a formal indirect treatment comparison using data from the 3 key trials (Randomized Evaluation of Long-Term Anticoagulation Therapy, Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation, and Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) of the NOACs. Data from the rivaroxaban trial were adjusted for the difference in international normalized ratio control among warfarin patients versus the other 2 trials. Model outputs included total costs, event rates, and quality-adjusted life-years.. Among the patients taking NOACs, those taking dabigatran had the highest total QALYs (7.68 QALYs), followed by apixaban (7.63 QALYs) and rivaroxaban (7.47 QALYs). Patients taking dabigatran had the lowest total lifetime costs (£23,342), followed by apixaban (£24,014) and rivaroxaban (£25,220). The differences between dabigatran and apixaban were modest but consistent in sensitivity analyses, with the directionality only changing at the limits of the CIs for the relative risks of ischemic stroke or intracranial hemorrhage or when assuming that both treatment discontinuation and post-event disability rates differ by drug.. Dabigatran was found to be economically dominant over rivaroxaban and apixaban in the UK setting. These economic findings are based on relative clinical efficacy from an indirect treatment comparison and would benefit from any data of direct comparisons of the NOACs in the future.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Embolism; Hemorrhage; Humans; Models, Theoretical; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; Stroke; United Kingdom; Warfarin

We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin.. The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups.. Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Embolism; Female; Heart Failure; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Stroke; Ventricular Dysfunction, Left; Warfarin

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Drug Approval; Embolism; Germany; Humans; Middle Aged; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Stroke; Warfarin

Left atrial catheter ablation for patients with atrial fibrillation (AF) requires periprocedural anticoagulation to minimize thromboembolic complications. High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported, raising concerns regarding its safety during left atrial catheter ablation. We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin, at a single high-volume AF ablation center.. We performed a retrospective analysis on consecutive patients undergoing left atrial ablation at Vanderbilt Medical Center from January 2011 through August 2012 with a minimum follow-up of 3 months. Patient cohorts were divided into two groups, those utilizing dabigatran etexilate pre- and post-ablation and those undergoing ablation on dose-adjusted warfarin, with or without low-molecular-weight heparin bridging. Dabigatran was held 24-30 h pre-procedure and restarted 4-6 h after hemostasis was achieved. We evaluated all thromboembolic and bleeding complications at 3 months post-ablation.. A total of 254 patients underwent left atrial catheter ablation for atrial fibrillation or left atrial flutter. Periprocedural anticoagulation utilized dabigatran in 122 patients and warfarin in 135 patients. Three late thromboembolic complications occurred in the dabigatran group (2.5 %), compared with one (0.7 %) in the warfarin group (p = 0.28). The dabigatran group had similar minor bleeding (2.5 vs. 7.4 %, p = 0.07), major bleeding (1.6 vs. 0.7 %, p = 0.51), and composite of bleeding and thromboembolic complications (6.6 vs. 8.9 %, p = 0.49) when compared to warfarin. There were no acute thromboembolic complications in either group (<24 h post-ablation).. In patients undergoing left atrial catheter ablation for AF or left atrial flutter, use of periprocedural dabigatran etexilate provides a safe and effective anticoagulation strategy compared to warfarin. A prospective randomized study is warranted.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Benzimidazoles; beta-Alanine; Catheter Ablation; Comorbidity; Dabigatran; Embolism; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Premedication; Retrospective Studies; Risk Assessment; Stroke; Tennessee; Treatment Outcome; 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; Embolism; Female; Humans; Male; Morpholines; Stroke; Thiophenes; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Male; Morpholines; Stroke; Thiophenes; Warfarin

The optimal treatment strategy for patients with aortic atheroma is not well established because data regarding medical treatment for such patients are lacking, especially with respect to the Japanese population. The purpose of this study was to clarify the effects of medical treatment on the risk of embolic events and mortality in patients with severe aortic plaque.. We retrospectively investigated 75 consecutive patients with severe aortic plaque detected on transesophageal echocardiography (TEE) between 1995 and 2005. The occurrence of embolic events and all-cause death in the period after TEE was assessed. The cumulative incidence of subsequent embolic events and death was evaluated in relation to specific medical treatments, including statins, antiplatelet drugs and warfarin.. Embolic events occurred in 27 patients (36%) and death occurred in 37 patients (49%) during follow-up (5.6±3.0 years). The patients who experienced embolic events had a significantly higher prevalence of previous embolic events, atrial fibrillation and hemodialysis than the patients who did not experience embolic events. Univariate and multivariate analyses showed that the use of statins and/or antiplatelet drugs was significantly associated with a low incidence of death but not with a low incidence of embolic events. On the other hand, warfarin exhibited neither beneficial nor harmful effects on the incidence of embolic events or death.. Statin and antiplatelet drugs have beneficial effects on the prognosis of patients with severe aortic plaque diagnosed on TEE.

Topics: Aged; Aged, 80 and over; Aorta; Aortic Diseases; Atrial Fibrillation; Death, Sudden; Echocardiography, Transesophageal; Embolism; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Prevalence; Prognosis; Regression Analysis; Renal Dialysis; Retrospective Studies; Risk; Stroke; Treatment Outcome; Warfarin

The WATCHMAN® device was proven non-inferior to oral anticoagulation (OAT). However, periprocedural risks and uncertainty regarding patients with absolute contraindication for OAT limit the overall utilisation of this approach. We investigated the periprocedural safety of dual platelet inhibition and primary utilisation of larger device diameters in order to minimise peri-device leakage and repositioning of the device during the implantation process.. Since 2010, 59 consecutive patients have been treated with the WATCHMAN® device and followed for six months. In patients with contraindications to warfarin, dual antiplatelet therapy (DAPT) was used during the first 45 days after implantation instead of warfarin. Device size was chosen 15-30% greater than the LAA diameter in order to minimise device repositioning and leakage, and to prevent device embolisation. Small, non-trabecular recesses at the superior ridge towards the inferior, left pulmonary vein were regularly observed and followed by transoesophageal echo regarding thrombus formation. We observed a 3.3% rate of pericardial effusions and a 5% rate of thrombi at the device during the healing period of 45 days and no device embolisations. One thromboembolic event without clinical sequelae was observed during the six-month follow-up period. All patients stopped DAPT at six months as no primary or secondary leakage >5 mm around the device perimeter was observed.. Our data suggest that DAPT can be used safely during the first 45 days in patients with contraindications to warfarin. An algorithm employing larger devices in relation to the LAA ostium with consecutively larger compression improved procedural safety compared to the current standard regarding leakage and device repositioning.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Appendage; Embolism; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

Scores for cardio-embolic and bleeding risk in patients with atrial fibrillation are described in the literature. However, it is not clear how they co-classify elderly patients with multimorbidity, nor whether and how they affect the physician's decision on thromboprophylaxis.. Four scores for cardio-embolic and bleeding risks were retrospectively calculated for ≥ 65 year old patients with atrial fibrillation enrolled in the REPOSI registry. The co-classification of patients according to risk categories based on different score combinations was described and the relationship between risk categories tested. The association between the antithrombotic therapy received and the scores was investigated by logistic regressions and CART analyses.. At admission, among 543 patients the median scores (range) were: CHADS2 2 (0-6), CHA2DS2-VASc 4 (1-9), HEMORR2HAGES 3 (0-7), HAS-BLED 2 (1-6). Most of the patients were at high cardio-embolic/high-intermediate bleeding risk (70.5% combining CHADS2 and HEMORR2HAGES, 98.3% combining CHA2DS2-VASc and HAS-BLED). 50-60% of patients were classified in a cardio-embolic risk category higher than the bleeding risk category. In univariate and multivariable analyses, a higher bleeding score was negatively associated with warfarin prescription, and positively associated with aspirin prescription. The cardio-embolic scores were associated with the therapeutic choice only after adjusting for bleeding score or age.. REPOSI patients represented a population at high cardio-embolic and bleeding risks, but most of them were classified by the scores as having a higher cardio-embolic than bleeding risk. Yet, prescription and type of antithrombotic therapy appeared to be primarily dictated by the bleeding risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; Logistic Models; Male; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Risk Assessment; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Embolism; Female; Humans; Male; Platelet Aggregation Inhibitors; Pyridines; Stroke; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Embolism; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Dose-Response Relationship, Drug; Electrocardiography; Embolism; Female; Follow-Up Studies; Heart Rate; Humans; Male; Randomized Controlled Trials as Topic; Stroke; Tachycardia, Paroxysmal; Time Factors; Treatment Outcome; Warfarin

Topics: Benzimidazoles; beta-Alanine; Embolism; Humans; Stroke; Warfarin

Though atrial fibrillation (AF) is the most common sustained arrhythmia permanently; there is not enough data about the prevalence, frequency of risk factors, and adequacy of anticoagulant therapy. We aimed to investigate the prevalence of AF, the frequency of risk factors, adequacy of anticoagulant therapy in patients who were admitted to our outpatient tertiary cardiology clinic according to current guidelines.. Patients, admitted to our Cardiology outpatient clinic between January - June 2010 and had a history of AF were included to the study retrospectively. Patients' demographic findings, clinical AF classification, CHA2DS2VASC scores, treatments the measured INR values in last 12 months retrospectively and the success of anticoagulant therapy were evaluated.. Overall, 432 (9.1%) of 4721 patients had AF. Among them 253 (58.5%) patients were female, mean age was 70.4 years. Permanent AF was the most common type. The most common risk factor was hypertension (71.9%). CHA2DS2VASC score was ≥ 2 in 377 patients (87.2%) and 254 (67.3%) of those patients had absolutely indicated for anticoagulation therapy, were taking warfarin. Sixteen of 37 patients with one risk factor, and 10 of 18 patients without risk factors were also receiving warfarin. Although warfarin was indicated in 123 patients, 36 patients had contraindications, 13 patients refused anticoagulation, and warfarin was stopped in 5 patients because of noncompliance with treatment. 15.9% of patients were not on warfarin although anticoagulation was indicated and no contraindication. 83.5% patients INR levels were between therapeutic ranges.. Anticoagulation is applied successfully among an important part of AF patients in our tertiary center, but in a substantial group of patients the guidelines are still not implemented. New, cost-effective, safe, accessible treatments are needed for warfarin contraindicated patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Male; Middle Aged; Practice Guidelines as Topic; Retrospective Studies; Risk Factors; Severity of Illness Index; Turkey; Warfarin

Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.. We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (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]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban.. An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Evidence-Based Medicine; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Time Factors; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Male; Morpholines; Rivaroxaban; Stroke; Thiophenes; Warfarin

Canadian patients with atrial fibrillation (AF) in whom anticoagulation is appropriate have two new choices for anticoagulation for prevention of stroke and systemic embolism--dabigatran etexilate (dabigatran) and rivaroxaban. Based on the RE-LY and ROCKET AF trial results, we investigated the cost-effectiveness of dabigatran (twice daily dosing of 150 mg or 110 mg based on patient age) versus rivaroxaban from a Canadian payer perspective. A formal indirect treatment comparison (ITC) of dabigatran versus rivaroxaban was performed, using dabigatran clinical event rates from RE-LY for the safety-on-treatment population, adjusted to the ROCKET AF population. A previously described Markov model was modified to simulate anticoagulation treatment using ITC results as inputs. Model outputs included total costs, event rates, and quality-adjusted life-years (QALYs). The ITC found when compared to rivaroxaban, dabigatran had a lower risk of intracranial haemorrhage (ICH) (relative risk [RR] = 0.38; 95% confidence interval [CI] 0.21 - 0.67) and stroke (RR = 0.62; 95%CI 0.45-0.87). Over a lifetime horizon, the model found dabigatran-treated patients experienced fewer ICHs (0.33 dabigatran vs. 0.71 rivaroxaban) and ischaemic strokes (3.40 vs. 3.96) per 100 patient-years, and accrued more QALYs (6.17 vs. 6.01). Dabigatran-treated patients had lower acute care and long-term follow-up costs per patient ($52,314 vs. $53,638) which more than offset differences in drug costs ($7,299 vs. $6,128). In probabilistic analysis, dabigatran had high probability of being the most cost-effective therapy at common thresholds of willingness-to-pay (93% at a $20,000/QALY threshold). This study found dabigatran is economically dominant versus rivaroxaban for prevention of stroke and systemic embolism among Canadian AF patients.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Canada; Clinical Trials as Topic; Cost-Benefit Analysis; Dabigatran; Embolism; Humans; Markov Chains; Models, Economic; Morpholines; Quality-Adjusted Life Years; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

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: Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Internationality; Male; Stroke; Warfarin

Topics: Aged; Angiography, Digital Subtraction; Angioplasty; Brachial Artery; Embolectomy; Embolism; Forearm; Hand; Heparin; Heparin, Low-Molecular-Weight; Humans; Ischemia; Male; Postoperative Care; Postoperative Complications; Radial Artery; Suction; Ulnar Artery; Ultrasonography, Doppler, Color; Urinary Bladder Neoplasms; Warfarin

A 44-year-old woman was admitted with the diagnosis of peripheral arterial emboli. Peripheral angiography demonstrated total occlusion of the popliteal artery. The obstruction was successfully resolved with a Fogarty arterial embolectomy catheter. Both transthoracic and transesophageal echocardiography showed a mobile, round thrombus in the noncoronary sinus of Valsalva. The patient did not accept surgery, and anticoagulation with warfarin was initiated. One month after treatment, transthoracic echocardiography demonstrated disappearance of the thrombus in the noncoronary sinus of Valsalva. The patient did not experience any recurrent episode of systemic embolization. This is a rare case of peripheral embolism caused by a thrombus in the noncoronary sinus of Valsalva without aneurysm.

Topics: Adult; Anticoagulants; Echocardiography, Transesophageal; Embolism; Female; Humans; Sinus of Valsalva; Thrombosis; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Approval; Embolism; Hemorrhage; Humans; Stroke; Therapeutic Equivalency; United States; United States Food and Drug Administration; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Drug Approval; Embolism; Humans; Practice Guidelines as Topic; Pyridines; Randomized Controlled Trials as Topic; Stroke; Warfarin

Ms TS is a 66-year-old woman who receives warfarin for prevention of systemic embolization in the setting of hypertension, diabetes, and atrial fibrillation. She had a transient ischemic attack about 4 years ago when she was receiving aspirin. Her INR control was excellent; however, over the past few months it has become erratic, and her average dose required to maintain an INR of 2.0 to 3.0 appears to have decreased. She has had back pain over this same period and has been taking acetaminophen at doses at large as 650 mg four times daily, with her dose varying based on her symptoms. You recall a potential interaction and wonder if (1) her acetaminophen use is contributing to her loss of INR control, and (2) does this interaction place her at increased risk of warfarin-related complications?

Topics: Acetaminophen; Aged; Analgesics, Non-Narcotic; Anticoagulants; Atrial Fibrillation; Back Pain; Biotransformation; Diabetes Complications; Drug Interactions; Drug Monitoring; Embolism; Female; Humans; Hypertension; International Normalized Ratio; Vitamin K; Warfarin

Dabigatran (Pradaxa) is a new oral anticoagulant approved in the United States for the primary prevention of stroke and systemic embolization in patients with nonvalvular atrial fibrillation. It offers clinicians an alternative to warfarin (Coumadin), and it has received considerable interest because of its convenience of use, clinical efficacy, and safety profile. However, it is more expensive, and this may limit its widespread use.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Embolism; Humans; Stroke; United States; Warfarin

Topics: Benzimidazoles; beta-Alanine; Embolism; Humans; Stroke; Warfarin

Topics: Anticoagulants; Asian People; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Embolism; Evidence-Based Medicine; Humans; International Normalized Ratio; Pakistan; Pyridines; Stroke; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is the most common clinically encountered arrhythmia in adults. Because it is associated with an increased risk of atrial thrombus formation and embolism, medical and/or electrical cardioversion is the preferred treatment method in the majority of clinics. Thrombus formation in the setting of AF most commonly occurs in the left atrial appendage (LAA), left atrium (LA), right atrial appendage (RAA), and right atrium in decreasing frequency. In routine transesophageal echocardiographic evaluation for AF, examination is generally limited to LA and LAA. Although relatively rare when compared with the left side, RAA thrombus has also the potential of embolism and should be screened. A case of RAA thrombus in which the LA and LAA were spared is described. The authors aimed to underline the importance of this rare but potentially dangerous complication of AF.

Topics: Aged; Atrial Appendage; Atrial Fibrillation; Contraindications; Dyspnea; Echocardiography, Transesophageal; Electric Countershock; Embolism; Female; Humans; Mitral Valve Insufficiency; Pulmonary Embolism; Thrombosis; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Echocardiography; Electrocardiography, Ambulatory; Embolism; Exercise Test; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticlopidine; Warfarin

Topics: Aged; Anticoagulants; Cholesterol; Embolism; Humans; Male; Syndrome; Toes; Warfarin

Ascending aorta and aortic arch thrombosis is rare in a young man with no risk factor. Here, we report the case of a young male patient with factor V Leiden mutation who developed ascending aorta and aortic arch thrombosis and subsequent emboli.

Topics: Adult; Anticoagulants; Aortic Diseases; Arterial Occlusive Diseases; Blood Coagulation; Blood Coagulation Disorders, Inherited; Echocardiography, Transesophageal; Embolism; Factor V; Humans; Lower Extremity; Male; Mutation; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Vascular Surgical Procedures; Warfarin

Percutaneous left atrial appendage (LAA) closure might reduce the cardioembolic risk in those patients with nonvalvular atrial fibrillation who are not candidates for warfarin therapy. This report presents the case of two patients with atrial fibrillation who had contraindications for warfarin therapy due to bleeding complications and a high cardioembolic risk (CHADS2 > or =2) who underwent successful LAA closure with a new device, the Amplatzer Cardiac Plug. The characteristics of the device and the main technical aspects of the procedure, as well as the potential advantages of this device for LAA closure, are discussed.

Topics: Aged; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Contraindications; Echocardiography, Doppler, Color; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Embolism; Female; Fibrinolytic Agents; Humans; Prosthesis Design; Radiography; Risk Assessment; Septal Occluder Device; Treatment Outcome; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Contraindications; Embolism; Fibrinolytic Agents; Humans; Patient Selection; Prosthesis Design; Risk Assessment; Septal Occluder Device; Treatment Outcome; Warfarin

Hemorrhage is a major complication of thrombolytic treatment. Concerns have been raised about the risk of hemorrhage in patients having received warfarin. Therefore, different indications for thrombolytic treatment are in use for stroke patients on warfarin. However, it remains uncertain whether the prior warfarin use actually increases their risk of bleeding in patients treated with thrombolysis.. This study included 179 consecutive patients who had high-risk cardioembolic sources and received thrombolytic treatment. Patients were treated with intravenous thrombolytic agents, or underwent intraarterial thrombolysis if their international normalized ratio (INR) was ≤1.7. We compared the frequency of bleeding complications between patients with prior warfarin use and those without. We also investigated whether there were differences in functional outcome and recanalization rates between them.. A prior warfarin use was present in 28 patients (15.6%). Although INR levels were higher in the prior warfarin group, the frequency of bleeding complications was not different between patients who received prior warfarin and those who did not. No differences were observed in patients with or without prior warfarin use, for successful recanalization rate (Thrombolysis in Myocardial Infarction grade 2 or 3), mortality, or modified Rankin score (≤2) at 3months.. Thrombolytic therapy for patients who previously received warfarin and had an INR≤1.7 did not affect bleeding risk, clinical outcome, or recanalization rate. Our data suggest that patients with a history of prior warfarin use may be safely treated with thrombolytic agents when their INR levels are low.

Topics: Adult; Aged; Aged, 80 and over; Aging; Anticoagulants; Brain Ischemia; Carotid Artery Thrombosis; Cerebral Angiography; Cerebral Hemorrhage; Embolism; Female; Fibrinolytic Agents; Heart; Humans; International Normalized Ratio; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis; Risk Factors; Sex Characteristics; Stroke; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Embolism; Humans; Pyridines; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

A 24-year-old male patient with anterior myocardial infarction, caused by embolization from mitral valve prosthesis due to inadequate anticoagulation is presented. The patient underwent cardiac catheterization within 90 minutes of arrival. Angiography showed total occlusion of the left anterior descending coronary artery (LAD) after the second diagonal branch. Thrombus was extracted with export catheter from LAD, and coronary artery perfusion was restored. The pain disappeared completely immediately after this intervention. Transoesophageal echocardiography performed 2 days later revealed no thrombus at the prosthetic valve. In conclusion, this case demonstrated that coronary embolism may occur even without prosthetic valve thrombus or dysfunction with suboptimal International Normalized Ratio levels, and can be successfully treated with coronary angiography with clot extraction with aspiration catheter (Export XT 6F Medtronic) only, without stenting.

Topics: Adrenergic beta-Antagonists; Adult; Angioplasty, Balloon; Anticoagulants; Antihypertensive Agents; Aspirin; Coronary Angiography; Coronary Artery Disease; Echocardiography, Transesophageal; Embolism; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Myocardial Infarction; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Chronic Disease; Embolism; Humans; Risk Assessment; Stroke; Time Factors; Treatment Outcome; Warfarin

The RE-LY study compared dabigatran in the dose of 150 mg and 110 mg twice daily, without laboratory monitoring, with the conventional treatment with warfarin dosed according to INR in 18,113 patients with non-valvular atrial fibrillation and high risk of embolisation. The incidence of cerebrovascular events and systemic embolisation was 1.69% per year in the warfarin group, compared to 1.53% per year in the 110 mg dabigatran group (relative risk 0.91; 95% CI 0.74-1.11; p < 0.001 for non-inferiority) and 1.11% per year in the 150 mg dabigatran (relative risk 0.66; 95% CI 0.53-0.82; p < 0.001 for superiority). Major bleeding occurred in 3.36% of patients per year in the warfarin group, compared to 2.71% of patients per year in the 110 mg dabigatran group (p = 0.003) and 3.11% of patients per year in the 150 mg dabigatran group (p = 0.31). Cerebral haemorrhagic events occurred in 0.38% of patients on warfarin per year, compared to 0.12% per year in the 110 mg dabigatran group (p < 0.001) and 0.10% per year in the 150 mg dabigatran group (p < 0.001). Mortality was 4.13% per year in the warfarin group, compared to 3.75% per year in patients on 110 mg dabigatran (p = 0.13) and 3.64% per year in patients on 150mg dabigatran (p = 0.051). In conclusion, administration of dabigatran to patients with atrial fibrillation in the dose of 110 mg in the RE-LY study was associated with the same incidence of cerebrovascular events and systemic embolisations as with warfarin, while there was lower incidence of major bleeding complications. Dabigatran in the dose of 150mg compared to warfarin led to reduction in the incidence of cerebral events and systemic embolisations with the same incidence of haemorrhagic complications.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Embolism; Humans; Pyridines; Warfarin

Topics: Age Factors; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Embolism; Hemorrhage; Humans; Incidence; International Normalized Ratio; Pyridines; Stroke; Warfarin

There is anecdotal evidence that fewer brachial and femoral embolectomies are being carried out. This may be because of the greater use of anticoagulation in patients with atrial fibrillation. The aim of the present study was to assess community-wide temporal trends in embolectomy of the extremities and of warfarin usage.. The Western Australian Linked Data System was used to identify cases of extremity embolectomy with a combination of diagnosis (upper or lower limb embolus) and procedure (embolectomy and revascularization) codes. Trends in age-specific and age-standardized rates were assessed over the period 1992-2003. Data regarding warfarin prescriptions were acquired from the Pharmaceutical Benefits Schedule database for the period 2000-2005.. One thousand and five patients aged 30 years and more underwent an embolectomy of the extremity during the study period. The age-specific rate of embolectomy increased from 0.78 per 100,000 in the 30- to 49-year-old group to 46.1 per 100,000 for those aged 80 years and more. There was a significant downward trend between 1992 and 2003 (Cuzik's trend test P = 0.015). This pattern was seen for all age groups. Prescriptions for warfarin increased by 50.4% over the period 2000-2005.. The rates of embolectomy of the extremity appear to be falling. Although the cause for this trend is not known, one possible explanation is increasing prescription of warfarin.

Topics: Age Distribution; Anticoagulants; Atrial Fibrillation; Embolectomy; Embolism; Extremities; Humans; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Dyspnea; Echocardiography; Electrocardiography; Embolism; Enoxaparin; Female; Humans; Radiography, Thoracic; Warfarin

There is limited information about distribution of etiologies of ischemic stroke in different age groups.. In this study, we applied the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in 87 patients aged < or = 45, and in 347 patients aged 46-60 years with first-ever ischemic stroke in order to follow the distribution of stroke etiologies in different age groups.. Traditional risk factors, except smoking and atrial fibrillation, were more frequent in older patients. The most frequent etiologies in the younger stroke patients (aged < or = 45) were 'other' than routine causes (26.4%), cardioembolism (22.4%) and 'idiopathic' strokes (20.7%), when no cause was found. In older patients (aged 46-60), small vessel disease (25.1%) and cardioembolism (22.2%) were the most frequent etiologies of stroke.. In stroke patients below the age of 45, the TOAST classification should be expanded to better classify the wide diversity of stroke etiologies. The relatively low frequency of routine stroke etiologies in patients aged < or = 45 can be explained by the significantly lower prevalence of traditional risk factors in these patients. In patients 46-60 years old, the TOAST classification is adequate in the characterization of ischemic stroke etiologies.

Topics: Adult; Age Distribution; Aging; Anticoagulants; Aspirin; Atrial Fibrillation; Embolism; Female; Foramen Ovale; Humans; Male; Middle Aged; Registries; Retrospective Studies; Risk Factors; Stroke; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Embolism; Heparin; Humans; Infarction; Intestinal Pseudo-Obstruction; Kidney; Male; Peripheral Vascular Diseases; Warfarin

Non-obstructive prosthetic valve thrombosis is a rare and underestimated complication in patients with left-sided mechanical heart valves. Systemic embolisation, mainly involving the cerebral circulation, often represents the first clinical manifestation. We report a case of multiple, successive embolizations in the coronary and cerebral circulation, presenting with an acute myocardial infarction and stroke in a patient with latent, non-obstructive thrombosis of a mechanical bileaflet aortic valve. Because of scheduled urological surgery, chronic vitamin K antagonist treatment had previously been discontinued and replaced with low-molecular-weight heparin, at inadequate dosage. Following coronary arteriography, brain computed tomography scan and transoesophageal echocardiography, thrombolysis was performed successfully. This case emphasises the utility of performing transoesophageal echocardiography routinely in the presence of ischaemic signs in patients with mechanical heart valves. In patients requiring discontinuation of oral anticoagulant therapy, accurate management and continuous monitoring of alternative medications are needed in order to avoid severe thromboembolic complications.

Topics: Aged; Anticoagulants; Aortic Valve; Drug Administration Schedule; Echocardiography, Doppler; Electrocardiography; Embolism; Heart Valve Prosthesis Implantation; Heparin, Low-Molecular-Weight; Humans; Male; Medical Errors; Myocardial Infarction; Stroke; Thrombosis; Warfarin

To show results of a prespecified pooled analysis of the studies SPORTIF III (open-label) and SPORTIF V (double-blind), to assess the homogeneity of the results and to explore subgroup analyses and adverse events.. 7,329 patients with atrial fibrillation (AF) and >or=1 additional stroke risk factor were randomized to warfarin (international normalized ratio 2.0-3.0) or ximelagatran (36 mg twice daily). Over 11,346 patient-years (mean 18.5 months/patient), 184 patients developed primary events of stroke and systemic embolism (ximelagatran 1.62 vs. warfarin 1.65%/year; p = 0.94). Heterogeneity between trials with respect to the primary event rate (study-by-treatment interaction p = 0.026) was found. This could not be explained statistically by baseline patient characteristics or by treatment (except perhaps by the better anticoagulation with warfarin in SPORTIF V) and was not evident for secondary end-points. There was no conclusive difference in major bleeding rates (ximelagatran 1.88 vs. warfarin 2.46%/year; p = 0.054), but combined minor plus major bleeding was lower with ximelagatran (31.7 vs. 38.7%/year; p < 0.0001). Elevation of liver enzymes occurred more frequently in patients taking ximelagatran (6.1% vs. warfarin 0.8%; p < 0.0001) and was reversible except in rare cases.. Fixed-dose oral ximelagatran without coagulation monitoring prevented stroke and systemic embolism as effectively as warfarin in patients with AF. Differences in the results of the two trials might relate to consistency of warfarin anticoagulation, different degree of blinding in the two trials, other concomitant therapies or chance. Further investigation is required to explore the long-term safety profile of ximelagatran.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Embolism; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thrombin; Warfarin

Postoperative thromboembolic complications associated with mechanical valve prosthesis implantation can be reduced with either antiplatelet agents or warfarin. Warfarin been shown to be more effective in adults, but the data are less clear in the pediatric population.. Seventy-two children and adolescents who survived mechanical valve implantation on the left side of the heart at the authors' institution were followed prospectively from August 1979 until December 2003. All patients underwent surgery before the age of 20 years, and follow up was included up to the age of 20 years. Initially, 53 patients received warfarin alone; mean follow up was 5.9 years, and total follow up 312 patient-years (pt-yr). Likewise, 19 patients received antiplatelet agents; mean follow up was 5.2 years, and total follow up 99 pt-yr. Results were examined using intent-to-treat analyses.. Age, gender, race, valve size and position, mean time of follow up and crossover rates were not different between groups. No differences were detected in survival or freedom from thromboembolic and hemorrhagic events. Complications associated with warfarin use were substantially more severe than those associated with antiplatelet agents.. The study results were inconclusive due to the small numbers of patient-years of follow up, but suggest that antiplatelet agents may be associated with less severe complications than warfarin. Moreover, warfarin and antiplatelet agents may be equally effective for clotting prophylaxis in children after valve replacement with St. Jude Medical prostheses.

Topics: Adolescent; Adult; Anticoagulants; Child; Child, Preschool; Disease-Free Survival; Embolism; Female; Heart Valve Prosthesis Implantation; Humans; Infant; Male; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Thrombosis; Treatment Outcome; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Embolism; Genetic Therapy; Hemophilia A; Humans; Pulmonary Embolism; Thrombophilia; Thrombosis; Vena Cava Filters; Warfarin

Mechanical valves are inherently thrombogenic and require meticulous anticoagulation. Pregnancy produces a hypercoagulable state and achieving adequate anticoagulation is difficult. We present a pregnant patient who had a nonobstructive thrombus of mechanical mitral valve causing embolic acute myocardial infarction. Issues surrounding management of anticoagulation and use of thrombolytic therapy during pregnancy are discussed. Education regarding the critical nature of adequate anticoagulation in these patients is important.

Topics: Adult; Anticoagulants; Cardiomyopathy, Hypertrophic; Echocardiography, Transesophageal; Embolism; Endocarditis; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Myocardial Infarction; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Warfarin

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available.. We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines.. The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year).. Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Azetidines; Benzylamines; Drug Therapy, Combination; Embolism; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Treatment Outcome; Warfarin

Topics: Atrial Fibrillation; Azetidines; Benzylamines; Embolism; Humans; Randomized Controlled Trials as Topic; Warfarin

Patients with cardiogenic sources of embolism may be at increased risk of cerebral infarction when anticoagulation therapy is suspended for surgical procedures. The purpose of this study was to determine frequency of cardioembolic cerebral infarction during periprocedural warfarin withdrawal.. Retrospective analysis of prospective cerebral infarction registry data from two tertiary medical centers.. Over a 12-month period, 14 cases of cardioembolic cerebral infarction occurring during the period of warfarin withdrawal for a medical procedure were observed, accounting for 7.1% of the 197 cardioembolic cerebral infarctions encountered. Across all patients, cerebral infarctions developed an average of 5.4 days after the last dose of warfarin (range 3-8). Among the 14 patients (8 males and 6 females) with warfarin cessation-related infarcts, age ranged from 54 to 91 years. Each had been on chronic anticoagulation with warfarin for more than 1 year. Retrospective analysis suggested that all these cerebral infarctions had been potentially preventable. In each case, either the planned procedure did not require discontinuation of warfarin or, when withdrawal was required, no bridging, parenteral anticoagulation was provided to lessen the risk during the warfarin-free period.. Patients at high risk of cardioembolic cerebral infarction may benefit from more intensive management strategies to reduce cerebral infarction risk during periprocedural periods.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cerebral Infarction; Coronary Disease; Drug Administration Schedule; Embolism; Female; Humans; Incidence; Male; Middle Aged; Practice Guidelines as Topic; Preoperative Care; Registries; Retrospective Studies; Tomography, X-Ray Computed; Warfarin

Atrial septal defect (ASD) is a common diagnosis in adults undergoing surgical repair. The aim of the study was to determine if ocular symptoms following treatment are due to microemboli. The study group included 20 adult patients (9 men, 11 women, mean age 57.2 years) with ASD who had undergone successful closure with the Amplatzer occluder. Patients were treated with aspirin or warfarin during the 6 months after the procedure. All were evaluated neurologically and an ocular medical history was obtained. Ocular examination included the 120-point Humphery visual field. Transcranial Doppler (TCD) was performed to monitor the middle cerebral artery. Two patients complained of amaurosis fugax at 1 and 3 months after the procedure, and two patients complained of blurred vision at 3 and 4 months after the procedure. TCD performed within 24 h of the complaints revealed no abnormalities. In all patients, the neurological and ocular examinations, including the visual field test, were normal. In conclusion, microembolic events do not appear to be the cause of the ocular complaints in patients with ASD treated with Amplatzer occluder. Further studies in larger samples are needed to confirm these results.

Topics: Adult; Aged; Amaurosis Fugax; Anticoagulants; Aspirin; Atrial Fibrillation; Catheters, Indwelling; Echocardiography; Embolism; Embolization, Therapeutic; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Septal Defects, Atrial; Humans; Male; Middle Aged; Predictive Value of Tests; Retinal Vessels; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Vision, Low; Warfarin

Ximelagatran is a novel oral direct thrombin inhibitor that offers a number of advantages over the standard treatment, warfarin, in patients with atrial fibrillation. Two large clinical trials, one open-label (Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation [SPORTIF] III), one double-blind (SPORTIF V), have compared the efficacy and safety of fixed-dose ximelagatran without anticoagulation monitoring with dose-adjusted warfarin using a non-inferiority design. On the basis of the results, the investigators concluded that ximelagatran was just as effective as warfarin in preventing stroke or systemic embolism (the primary end point), because the pre-specified non-inferiority criterion was met. Reanalysis of the data with rather conservative interpretive criteria, however, revealed a number of deficiencies: 1) an unreasonably generous margin that was potentially biased toward non-inferiority, given the low baseline event rate of warfarin; 2) the inappropriateness of the analytical method used to estimate the non-inferiority margin; 3) a lack of confidence that ximelagatran retains at least 50% of warfarin's effect (a prerequisite to the establishment of non-inferiority); 4) significant heterogeneity in the magnitude of efficacy observed in the two trials; and 5) safety concerns regarding increased liver toxicity with ximelagatran without a significant offsetting advantage in major bleeding. This imbalance in the benefit-risk profile materially undermines the investigators' claim of non-inferiority of ximelagatran and led the Food and Drug Administration to reject the sponsor's application for ximelagatran. Despite published conclusions to the contrary, we conclude that ximelagatran has not been shown to be non-inferior to warfarin. Such determinations of non-inferiority are highly dependent on the underlying assumptions, and graphical sensitivity analyses make this dependence explicit.

Topics: Anticoagulants; Azetidines; Bayes Theorem; Benzylamines; Embolism; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Sample Size; Stroke; Treatment Outcome; Warfarin

Although warfarin reduces embolic events in patients with nonvalvular atrial fibrillation (NVAF), it is used less frequently in Japan and so the aim of the present study was to determine the attitudes of Japanese cardiologists toward antithrombotic therapy for NVAF patients.. Subjects were NVAF patients enrolled in a prospective study in 1999. Clinical characteristics, type of NVAF and antithrombotic therapy, risk factors for embolism, and contraindications to warfarin were analyzed. Risk factors included advanced age (>75 years), hypertension, diabetes mellitus, congestive heart failure, and prior embolic events. Contraindications to warfarin included bleeding tendency, malignant tumors and others. Among 509 patients (66.6+/-10.3 years old), 359 had at least one risk factor for embolism and of these 359 patients, 200 (55.7%) received warfarin (ie, modest adherence to the guideline for antithrombotic therapy). There were 159 patients who had at least one risk factor but did not receive warfarin; 70.4% of these received antiplatelet drugs. Contraindications were found in only 22.6% and paroxysmal nature of NVAF seemed a possible reason for non-use of warfarin in 47.2% of 159 patients.. In Japan warfarin is not used extensively for treatment of NVAF patients having risk factors and the reasons for not using antithrombotic therapy seemed inappropriate in most of patients.

Topics: Anticoagulants; Atrial Fibrillation; Attitude of Health Personnel; Cardiology; Contraindications; Embolism; Health Services Misuse; Humans; Japan; Physicians; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Warfarin

Topics: Ambulatory Care; Ambulatory Care Facilities; Anticoagulants; Child; Child, Preschool; Clinical Trials as Topic; Embolism; Hemorrhage; Humans; Infant; Pediatrics; Thrombosis; Warfarin

It is very important to prevent embolisms from left atrial thrombi (LAT). The present study was a trial for the management of patients with AT using 122 patients with atrial fibrillation and LAT who were followed for 1 year after transesophageal echocardiography. LAT were classified by their shape and mobility into the mobile ball type (MB, n=28), fixed ball type (FB, n=32) and mountain type (MO, n=42). The patients were given warfarin (INR: 1.5-2.0, n=43), aspirin 81 mg (n=74) and/or ticlopidine 200 mg/day (n=31). The embolic rate (ER) in the MB group was significantly higher than in the other groups [ie, MB 39.3% vs FB 15.6% (p<0.05), vs MO 2.4% (p<0.05)]. The ER in the FB group was significantly higher than in the MO group (p<0.05). Therapy with a combination of ticlopidine and aspirin reduced the ER in the patients with ball thrombi. The ER of the ball thrombus type group, especially the MB group, was very high in spite of therapy with anti-coagulants and/or anti-platelet agents, and such patients should be treated by early surgical intervention. However, the combination of ticlopidine and aspirin may be useful for preventing embolism.

Topics: Aged; Aspirin; Atrial Fibrillation; Disease-Free Survival; Drug Therapy, Combination; Echocardiography, Transesophageal; Embolism; Female; Heart Atria; Humans; Male; Middle Aged; Practice Guidelines as Topic; Predictive Value of Tests; Survival Analysis; Thrombosis; Ticlopidine; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Embolism; Endpoint Determination; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recurrence; Survival Analysis; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Embolism; Endpoint Determination; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recurrence; Survival Analysis; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Embolism; Endpoint Determination; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Neoplasms; Recurrence; Survival Analysis; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Dose-Response Relationship, Drug; Embolism; Humans; International Normalized Ratio; Stroke; Warfarin

The goal of this study was to identify the factors responsible for embolic complications of direct current (DC) cardioversion of atrial arrhythmias.. Direct current cardioversion of atrial fibrillation (AF) carries a risk of thromboembolism, which is reduced, but not eliminated, by anticoagulation. The risk of embolism after conversion of atrial flutter is believed to be lower. No series to date has included enough patients receiving anticoagulants or enough patients with atrial flutter to estimate the risk in these groups.. We reviewed the case records of 1,950 patients who underwent 2,639 attempts at DC cardioversion.. Cardioversion was performed within two days of the apparent onset of the arrhythmia in 443 episodes, 352 without subsequent prolonged anticoagulation with one embolic complication. Cardioversion was preceded by warfarin therapy for > or = 3 weeks in 1,932 instances. No embolic complication occurred in 779 attempts performed with an international normalized ratio (INR) of > or = 2.5 (95% confidence limits 0% to 0.48%). Of 756 cases in which the INR was <2.5 or was not measured before conversion, nine were complicated by thromboembolism. Embolism was significantly more common at an INR of 1.5 to 2.4 than at an INR > or = 2.5 (0.93% vs. 0%, p = 0.012). The incidence of embolism after conversion of atrial flutter or tachycardia was similar to that after cardioversion of AF (0.72% vs. 0.46%, p = NS).. The INR should be > or = 2.5 at the time of cardioversion if the duration of AF is uncertain or >2 days. Cardioversion of atrial flutter presents similar risks and requires similar anticoagulation.

Topics: Anticoagulants; Atrial Fibrillation; Atrial Flutter; Electric Countershock; Embolism; Female; Humans; Male; Middle Aged; Warfarin

Severe aortic plaques seen on transesophageal echocardiography (TEE) are a high-risk cause of stroke and peripheral embolization. Evidence to guide therapy is lacking. Retrospective information was obtained regarding the occurrence of embolic events (stroke, transient ischemic attacks, or peripheral emboli) in 519 patients with severe thoracic aortic plaque seen on TEE since 1988. Treatment with statins, warfarin, or antiplatelet medications was noted. Treatment was not randomized. In a matched-paired analysis, each patient taking each class of therapy was matched for age, gender, previous embolic event, hypertension, diabetes, congestive failure, and atrial fibrillation to someone not taking that medication. Multivariate analysis was also performed. An embolic event occurred in 111 patients (21%). Multivariate analysis showed that statin use was independently protective against recurrent events (p = 0.0001). Matched analysis also showed a protective effect of statins (p = 0.0004; absolute risk reduction 17%, relative risk reduction 59%, number needed to treat [n = 6]). No protective effect was found for warfarin or antiplatelet drugs. The odds ratio for embolic events was 0.3 (95% confidence interval [CI] 0.2 to 0.6) for statin therapy, 0.7 (95% CI 0.4 to 1.2) for warfarin, and 1.4 (95% CI 0.8 to 2.4) for antiplatelet agents. Thus, there is a protective effect of statin therapy, and no significant benefit of warfarin or antiplatelet drugs on the incidence of stroke and other embolic events in patients with severe thoracic aortic plaque on TEE.

Topics: Aged; Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Echocardiography, Transesophageal; Embolism; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Longitudinal Studies; Male; Multivariate Analysis; Odds Ratio; Platelet Aggregation Inhibitors; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

Antiphospholipid syndrome is characterized by venous and arterial thrombosis. Antiphospholipid antibodies are essential to making the diagnosis. It may be a primary disorder or it may be secondary to a connective tissue disorder. Cardiac manifestations of this syndrome include both thrombotic and degenerative valvular disease. Systemic or pulmonary embolism, as well as intravascular thrombosis, is a significant cause of morbidity and mortality. We present a case of renal infarction in a woman with polymyalgia rheumatica and a positive test for antiphospholipid antibody.

Topics: Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Atrial Fibrillation; Embolism; Female; Humans; Infarction; Kidney; Polymyalgia Rheumatica; Renal Artery; Tomography, X-Ray Computed; Warfarin

We sought to assess the occurrence and clinical significance of stroke and peripheral arterial embolizations at non-central nervous system sites in a large, community-based cohort with hypertrophic cardiomyopathy (HCM).. Such vascular events are insufficiently appreciated complications of HCM for which there is limited information on occurrence, clinical profile and determinants.. We assessed the clinical features of patients with stroke and other peripheral vascular events in a consecutive group of patients with HCM from four regional cohorts not subject to significant tertiary referral bias.. Of the 900 patients, 51 (6%) patients experienced stroke or other vascular events over 7 +/- 7 years, including 44 patients with stroke; 21 (41%) of these 51 patients died or were permanently disabled. The overall incidence was 0.8%/year and 1.9% for patients >60 years old. Age at first event ranged from 29 to 86 years (mean 61 +/- 14 years). Most (n = 37; 72%) events occurred in those >50 years, although 14 (28%) younger patients (< or = 50 years) also had events. Multivariate analysis showed stroke and other peripheral vascular events to be independently associated with congestive symptoms and advanced age, as well as with atrial fibrillation (in 45 [88%] of 51 patients), at the initial evaluation. The cumulative incidence of these events among patients with atrial fibrillation was significantly higher in non-anticoagulated patients as compared with patients receiving warfarin (31% vs. 18%; p < 0.05).. Stroke and peripheral embolizations showed a 6% prevalence rate and an incidence of 0.8%/year in a large, unselected HCM group. These profound complications of HCM, which may lead to disability and death, were substantially more common in the elderly, occurred almost exclusively in patients with paroxysmal or chronic atrial fibrillation and appeared to be reduced in frequency by anticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiomyopathy, Hypertrophic; Embolism; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Assessment; Stroke; Warfarin

A prospective study to determine the prevalence of embolic signals (ES) detected with transcranial Doppler ultrasound (TCD) in subjects with non-valvular atrial fibrillation (NVAF) who were and were not taking anticoagulants.. Sixty-eight subjects with NVAF taking warfarin and sixty-three NVAF subjects not taking warfarin were recruited from the cardiology department. No patients had suffered a previous stroke or clinical systemic embolisation. Thirty subjects in sinus rhythm were recruited as controls. TCD recordings were performed bilaterally from the middle cerebral arteries for 1 h. In 126 subjects (96%) the recording was repeated 1 week later. All Doppler recordings were reviewed blindly by an observer for ES.. After one recording ES were detected in one warfarin NVAF subject (1.5%), four non-warfarin NVAF subjects (6.3%) and no sinus rhythm controls. Following both recordings ES were detected in one warfarin NVAF subject (1.5%) and seven non-warfarin NVAF subjects (11.9%) P = 0.017.. Asymptomatic ES can be detected in a minority of subjects with NVAF. These signals were significantly less common in NVAF subjects taking warfarin, and this is consistent with asymptomatic ES having clinical significance in this disease. TCD detection of ES may have application in patients with NVAF for risk stratification, and assessment of the efficacy of new anti-platelet and anti-thrombotic regimens in the condition. Further large prospective studies are required to determine whether ES predict stroke risk in this patient group.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Embolism; Female; Humans; Male; Prospective Studies; Ultrasonography, Doppler, Transcranial; Warfarin

Topics: Anticoagulants; Aspirin; Brain Ischemia; Data Interpretation, Statistical; Embolism; Endpoint Determination; Humans; Odds Ratio; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Research Design; Secondary Prevention; Sensitivity and Specificity; Stroke; Treatment Outcome; Warfarin

Atrial fibrillation is a major risk factor for stroke. Anticoagulant therapy reduces this risk but increases the risk of haemorrhage. We aimed to compare the morbidity related to the treatment of atrial fibrillation with warfarin seen in one year at our hospital, with the morbidity in those patients in whom embolism was potentially preventable. There were 111 patients admitted to our hospital in a 12 month period with nonvalvular atrial fibrillation (NVAF) who had stroke, TIA or peripheral embolism. Atrial fibrillation was identified prior to admission in 87 of these 111 (78%) patients with thromboembolism, yet only 14 of these (16%) were receiving warfarin for stroke prophylaxis. Through chart review, a further 56 (64%) patients with embolism could have been receiving anticoagulant therapy if published clinical guidelines(1) were applied. Therefore, 40 episodes of thromboembolism were potentially preventable. Over the same period, there were 18 patients admitted with haemorrhage related to warfarin therapy for stroke prophylaxis in NVAF, including 10 gastrointestinal, five intracerebral, and three peripheral haemorrhages. Most haemorrhages were associated with a high International Normalized Ratio (INR) and the patients were left less disabled than those with embolism. Only one patient with haemorrhage had an absolute contraindication to warfarin therapy (6%). We conclude that the number of preventable strokes far outweighed the morbidity due to warfarin use in the management of NVAF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Australia; Embolism; Hemorrhage; Hospitalization; Humans; Incidence; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Thromboembolism; Warfarin

Topics: Administration, Oral; Anticoagulants; Dicumarol; Embolism; Follow-Up Studies; Humans; Incidence; Neoplasms; Pulmonary Embolism; Risk Factors; Thrombosis; Time Factors; Warfarin

The present study, which aimed to determine the predictors of distal embolization and restenosis after stenting for vein graft disease, retrospectively analyzed 51 consecutive patients who underwent stent implantation for diseased saphenous vein grafts. Follow-up angiography was performed 6 months after the procedure and the clinical and angiographic variables were analyzed by multivariate logistic regression to determine the predictors of distal embolization and restenosis. Initial clinical success was achieved in 49 patients, 44 of whom underwent follow-up angiography and were enrolled in the retrospective analysis. Distal embolization occurred in 6 grafts (13.6%). Multivariate analysis showed that the lesion length and the total cholesterol level were independent predictors of distal embolization. Angiographic restenosis occurred in 13 (26.5%) of 49 lesions. The minimum luminal diameter and the percent diameter stenosis after stenting were associated with the occurrence of restenosis. Multivariate analysis of lesions located in the graft body identified graft age as an independent predictor of restenosis. Distal embolization can occur after vein graft stenting, especially in patients with hypercholesterolemia and diffuse stenosis. The post-stenting minimum luminal diameter and the percent diameter stenosis are predictors of restenosis. In particular, graft age is associated with the restenosis of graft body lesions.

Topics: Aged; Anticoagulants; Aspirin; Catheterization; Combined Modality Therapy; Comorbidity; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Drug Therapy, Combination; Embolism; Female; Fibrinolytic Agents; Follow-Up Studies; Graft Occlusion, Vascular; Heparin; Humans; Japan; Male; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Saphenous Vein; Stents; Ticlopidine; Treatment Outcome; Warfarin

The clinical presentation of patients with acute lower-limb ischemia and primary aortic thrombus prompted this review. Following recognition of the first case in early 1994, relevant patients (n = 6) were kept in a database and were reviewed for presentation, treatment, and follow-up. The median age was 41 and five patients were male. Angiography, computed tomography, and/or magnetic resonance angiography demonstrated one or more aortic sessile or pedunculated thrombus(i) without associated atherosclerotic disease. In two cases, a retropancreatic intraaortic mural thrombus was associated with severe pancreatitis. All other cases presented with acute lower-limb emboli requiring limb salvage embolectomy. Because of significant patient illness, systemic anticoagulation was chosen acutely to prevent recurrent emboli. Interestingly, serial studies demonstrated aortic thrombus resolution. Failure to continue warfarin therapy resulted in recurrent problems (n = 1) unless the instigating event had resolved (n = 3). There were no deaths or amputations. We concluded that surgical embolectomy, when required, with subsequent anticoagulation, results in limb salvage and allows for eventual resolution of the primary aortic thrombus. Long-term anticoagulation is required unless the etiologic process resolves. The literature describes patients with atherosclerosis and overlying thrombus but fails to describe the approach to patients with primary thrombus formation.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Aorta, Abdominal; Aortic Diseases; Embolectomy; Embolism; Female; Heparin; Humans; Leg; Male; Pancreatitis; Thrombosis; Warfarin

In general, aspirin is indicated to prevent thrombosis in conditions associated with high shear rates (i.e., atherosclerosis) and warfarin is indicated to prevent thrombosis in conditions associated with stasis (i.e., atrial fibrillation). While aspirin and warfarin should generally not be used together, their combined use is beneficial in selected patients (e.g., some patients with mechanical valve prostheses). Aspirin in a dose of 75-150 mg per day is indicated to prevent vascular events in patients with ischaemic heart disease and also in patients at high risk of ischaemic heart disease. All patients with atrial fibrillation should be considered for oral anticoagulant therapy, with the decision for its use based on an assessment of the balance between the risk of thromboembolism and bleeding. The recommended therapeutic INR (international normalised ratio) range in non-valvular atrial fibrillation is 2.0-3.0. Warfarin is contraindicated in pregnancy, particularly during the first trimester; however, it may still need to be used in the second and third trimesters in patients with mechanical valve prostheses.

Topics: Aged; Anticoagulants; Aspirin; Embolism; Female; Heart Diseases; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thrombosis; Warfarin

Recent atrial fibrillation guidelines recommend the incorporation of patient preferences into the selection of antithrombotic therapy. However, no trial has examined how incorporating such preferences would affect quality-adjusted survival or medical expenditure. We compared 10-year projections of quality-adjusted survival and medical expenditure associated with two atrial fibrillation treatment strategies: warfarin-for-all therapy versus preference-based therapy. The preference-based strategy prescribed whichever antithrombotic therapy, warfarin or aspirin, had the greater projected quality-adjusted survival.. We used decision analysis stratified by the number of stroke risk factors (history of stroke, transient ischemic attack, hypertension, diabetes, or heart disease). The base case focused on compliant 65-year-old patients who had nonvalvular atrial fibrillation and no contraindications to antithrombotic therapy.. In patients whose only risk factor for stroke was atrial fibrillation, preference-based therapy improved projected quality-adjusted survival by 0.05 quality-adjusted life year (QALY) and saved $670. For patients who had atrial fibrillation and one additional risk factor for stroke, preference-based therapy improved quality-adjusted survival by 0.02 QALY and saved $90. In patients who had atrial fibrillation and multiple additional risk factors for stroke, preference-based therapy increased medical expenditures and did not improve quality-adjusted survival substantially. The benefits of preference-flexible therapy arose from the minority of patients who would have had a longer quality-adjusted survival if they had been prescribed aspirin rather than warfarin.. As do risks of stroke and of hemorrhage, patients' preferences help to determine which antithrombotic therapy is optimal. Preference-based treatment should improve quality-adjusted survival and reduce medical expenditure in patients who have nonvalvular atrial fibrillation and not more than one additional risk factor for stroke.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Cohort Studies; Cost-Benefit Analysis; Decision Trees; Embolism; Female; Health Care Costs; Humans; Male; Middle Aged; Patient Satisfaction; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Thrombolytic Therapy; Warfarin

Aortic root replacement (ARR) is a technically demanding procedure that can be performed using a variety of prosthetic devices. Root replacement in the young, but grown-up, patient poses unique problems in terms of the long-term outcome and active lifestyle that must be guaranteed by this operation. To identify the "ideal" substitute for ARR in the young, clinical results in teenagers and young adults (<35 years) operated on in the past two decades were reviewed.. Thirty-eight patients younger than 35 years underwent ARR between January 1980 and December 1996. Eighteen patients, aged 30+/-5 years, had ARR with composite graft (group 1), whereas 20 patients, aged 28+/-6 years, had ARR with aortic homografts or pulmonary autografts (group 2). Primary indication for the operation was aortic insufficiency with anuloaortic ectasia (12 of 18) in group 1 and aortic insufficiency with or without anuloaortic ectasia (16 of 20) in group 2. Urgent ARR was required in 3 (17%) group 1 patients and 1 (5%) group 2 patient (p = 0.01).. Operative deaths were 2 (11%) in group 1, caused by hemorrhage and low output, and none in group 2. There were 4 (25%) late deaths in group 1, caused by embolism (2), hemorrhage, and myocardial infarction, and 1 (5%) in group 2, caused by arrhythmia. Survival was 81% +/- 9%, and 55%+/-18% at 2 and 10 years in group 1 versus 94%+/-5% at 2 years in group 2 (p = 0.04). Freedom from valve-related events was 93%+/-6% and 62%+/-18% at 2 and 10 years in group 1 versus 100% at 2 years in group 2 (p = 0.02). Freedom from reoperation in group 1 was 75% +/- 22% at 10 years, whereas no reoperations were done in group 2. Seven (58%) group 1 patients versus 1 (5%) group 2 patient were on cardiac medications (p = 0.001), and 11 (92%) group 1 patients versus no group 2 patients were on warfarin therapy at follow-up. All survivors were back to school or prior employment.. Survival early after ARR does not differ depending on the type of prosthesis. Valve-related events are common, and reoperation may be needed late after ARR with composite grafts. Despite limited follow-up with biologic devices, the prevalence of complications with composite grafts makes homograft or autograft ARR preferable in adolescents and young adults.

Topics: Adolescent; Adult; Age Factors; Anticoagulants; Aortic Valve; Aortic Valve Insufficiency; Bioprosthesis; Cardiac Output, Low; Cause of Death; Embolism; Female; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Life Style; Longitudinal Studies; Male; Myocardial Infarction; Postoperative Complications; Postoperative Hemorrhage; Pulmonary Valve; Reoperation; Retrospective Studies; Risk Factors; Survival Rate; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Warfarin

Patients with left atrial thrombus are considered at high risk for thromboembolic events. The actual prognosis of these patients and the features most predictive of future events are unclear. We performed transesophageal echocardiograms in 2,894 patients over a 6 1/2-year period; 94 (age 69 +/- 11 years, 59 men, 83 in atrial fibrillation) were found to have left atrial thrombus. The thrombi were considered mobile in 45 patients and 33 patients had thrombus with a maximum dimension > or = 1.5 cm. Seven of the 94 patients with prosthetic valves were excluded from follow-up analysis. Over a follow-up period of 25.3 +/- 19.2 months, 17 patients had suffered a stroke or embolic event (event rate 10.4% per year) and 27 had died (mortality 15.8% per year). Cox proportional hazard regression analysis identified a maximum thrombus dimension > or = 1.5 cm (RR 19, p = 0.002), history of thromboembolism (RR 4.2, p = 0.038), and mobile thrombus (RR 5.3, p = 0.02) as predictors of subsequent thromboembolism. Moderate or severe left ventricular dysfunction was the only significant predictor of death (RR 2.9, p = 0.04). Gender, age, warfarin therapy at follow-up, atrial fibrillation, location (cavity vs appendage) of thrombus, and spontaneous echocardiographic contrast were not significant. Aggressive antithrombotic therapy may be indicated in these high-risk patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Echocardiography, Transesophageal; Embolism; Female; Fibrinolytic Agents; Follow-Up Studies; Forecasting; Heart Atria; Heart Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Prognosis; Proportional Hazards Models; Risk Factors; Sex Factors; Survival Rate; Thromboembolism; Thrombosis; Ventricular Dysfunction, Left; Warfarin

Recently, a change in anticoagulation therapy occurred that is still partially ignored by the healthcare community. Understanding the controversy over the use of the internal normalized ratio in monitoring patients receiving warfarin therapy is important for nurses who provide care to these patients. Five questions related to current monitoring of patients treated with anticoagulants are addressed. Nurses must recognize the importance to their practice of changes in laboratory methods and move toward using the most useful measures available to influence patients' outcomes. The international normalized ratio is the most appropriate way to evaluate the effects of warfarin therapy. All healthcare providers should use this ratio as the standard in evaluating the effects of anticoagulation therapy.

Topics: Anticoagulants; Drug Monitoring; Embolism; Humans; Prothrombin Time; Reference Standards; Thrombosis; Warfarin; World Health Organization

Stroke from surgically inaccessible intracranial atherostenosis remains a formidable clinical challenge. While antithrombotic or antiplatelet therapy may prevent distal embolism, there is no effective program for plaque stabilization preventing progression of atherosclerotic stenosis. In patients with isolated circulations (single vertebral with absent posterior communicating arteries, single carotid with contralateral internal carotid artery occlusion, or single carotid with an absent anterior communicating artery), occlusion of the stenotic vessel may produce a low flow-mediated stroke. Fifteen patients with atherosclerotic intracranial stenoses were treated by balloon angioplasty after medical therapy with warfarin failed. Treated territories included the distal internal carotid, proximal middle cerebral, distal vertebral, and basilar arteries. Dilation was successful in all vessels, with residual stenoses averaging less than 30%. Two complications included one paramedian pontine stroke and a single vessel rupture that proved fatal. There was no recurrence of transient ischemic attacks and no restenosis at the angioplasty site over a follow-up period of more than 24 months. In this small series, balloon angioplasty of intracranial vessels provided a therapeutic option for secondary stroke prevention in highly selected patients. Further studies will be necessary to establish the efficacy and safety of endovascular treatment in larger series.

Topics: Adult; Aged; Angioplasty, Balloon; Anticoagulants; Arteriosclerosis; Basilar Artery; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebral Arteries; Cerebrovascular Disorders; Disease Progression; Embolism; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Regional Blood Flow; Rupture; Vertebral Artery; Warfarin

We investigated the efficacy of the Jarvik 2000 intraventricular assist device (Jarvik Research, Inc., New York, N.Y.) in an ovine model. The device is an axial flow pump measuring 1.8 cm in diameter by 5 cm long, has a displacement volume of 12 ml, and can deliver flow from 2 to 7 L/min. Seven devices were implanted through a left thoracotomy into the left ventricle with an outflow graft to the descending aorta. Animals were treated with warfarin sodium and aspirin to maintain prothrombin times approximately 1.5 times control. Animals were followed up for 3 to 123 days. Two animals died of operative complications at days 3 and 5. One device failed at 58 days because of thrombus formation at the inflow side of the impeller. The remaining four animals were killed at days 19, 42, 42, and 123, respectively, because of broken electric power cables. Hematocrit values rose significantly higher than preoperative levels (22.8% +/- 3.8% to 30.5% +/- 3.4%); premortem elevations of values higher than baseline values of plasma free hemoglobin (10.4 +/- 7.8 mg/dl to 17.1 +/- 7.4 mg/dl) and lactate dehydrogenase (391.5 +/- 113.7 units/L to 771.2 +/- 370.8 units/L) were statistically insignificant. Serum creatinine and bilirubin levels were normal. No end-organ dysfunction arising from long-term support was evident clinically or at postmortem examination, nor was there any evidence of embolism or damage to intracardiac structures. We found the Jarvik 2000 intraventricular assist device to be easily implantable, safe, nonhemolytic, and able to provide physiologic flow with power requirements under 10 watts.

Topics: Adult; Animals; Anticoagulants; Aspirin; Blood Vessel Prosthesis; Child; Coronary Circulation; Electric Power Supplies; Embolism; Equipment Design; Heart-Assist Devices; Heparin; Humans; Polyethylene Terephthalates; Sheep; Thrombosis; Warfarin

Two patients experienced upper extremity thromboembolism after axillary-axillary bypass grafting (AxAG) for symptomatic subclavian artery stenosis. The first patient, a 67-year-old male, presented with left upper extremity thromboembolism 3 years after AxAG with 8 mm externally support PTFE. An arteriogram revealed a patent AxAG, thrombus in the proximal left subclavian arterial stump just distal to its occlusion, and multiple digital artery emboli. The patient was treated with warfarin for 8 months, with resolution of symptoms. The second patient, a 57-year-old male, occluded his AxAG (8 mm knitted Dacron) with minimal return of symptoms. Non-operative treatment was elected and 4 years later the patient presented with right upper extremity (donor side) thromboembolism. Arteriography revealed occlusion of the AxAG, radial artery, and digital arteries of the index, long and ring fingers. Thrombolytic therapy of the right arm was undertaken with minimal improvement. Subsequent detachment of the AxAG and placement of an interposition reversed saphenous vein graft was performed. Both patients continue to be asymptomatic during follow-up of 4.7 and 2.0 years, respectively.

Topics: Aged; Anticoagulants; Arm; Arterial Occlusive Diseases; Axillary Artery; Blood Vessel Prosthesis; Constriction, Pathologic; Embolism; Fingers; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Polytetrafluoroethylene; Postoperative Complications; Radial Artery; Saphenous Vein; Subclavian Artery; Thromboembolism; Thrombolytic Therapy; Thrombosis; Warfarin

Topics: Anticoagulants; Embolism; Embolism, Cholesterol; Humans; Pulmonary Embolism; Renal Insufficiency; Warfarin

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Drug Costs; Embolism; Humans; Patient Selection; Thrombosis; Treatment Outcome; Warfarin

A 75-year-old woman was admitted with transient left hemiparesis accompanied by diminished level of consciousness in September 1994. Holter electrocardiography showed transient atrial fibrillation, and transesophageal echocardiography (TEE) revealed an atrial septal aneurysm, spontaneous echo contrast, and a thrombus in the left atrial appendage. The patient received anticoagulant treatment with warfarin, and follow-up TEE showed thrombus resolution. However, after the warfarin was discontinued, symptoms recurred in October 1995 and TEE showed a club-like left atrial thrombus (21 x 40 mm) originating in the left atrial appendage and extending to the center of the left atrium. Follow-up TEE after warfarin therapy showed resolution at the neck of the thrombus but the head threatened detachment. The thrombus was subsequently excised surgically. Follow-up TEE was critical for detecting the risk of significant embolization during anticoagulant therapy.

Topics: Aged; Anticoagulants; Echocardiography, Transesophageal; Embolism; Female; Heart Atria; Heart Diseases; Humans; Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is characterized by venous and/or arterial thromboses in the presence of the lupus anticoagulant, anticardiolipin antibodies, or both. Antiphospholipid syndrome may occur as a primary disease or in patients with systemic lupus erythematosus or other autoimmune, infectious, or neoplastic disorders. This is a case of APS associated with chronic myelomonocytic leukemia and complicated by a large descending thoracic aorta thrombus responsible for lower limb and visceral emboli. The intraaortic clot was discovered by transesophageal echography (TEE). The association of APS with chronic leukemias has only rarely been described and, as far as can be ascertained, the location of a thrombus in the descending thoracic aorta has never been reported for this syndrome. This case illustrates the crucial role of TEE in the assessment of patients with systemic embolizations.

Topics: Aged; Animals; Antiphospholipid Syndrome; Aorta; Echocardiography, Transesophageal; Embolism; Heparin; Humans; Male; Thrombosis; Tomography, X-Ray; Warfarin

The aim of the study was to assess the role of oral anticoagulant therapy in patients with dilated cardiomyopathy at risk of embolic complications.. We studied retrospectively two hundred thirty-six patients with dilated cardiomyopathy; sixty-eight cases, with intracavitary thrombosis at cross-sectional echocardiography (17 patients), embolic episodes (22), N.Y.H.A. functional class IV (38), chronic atrial fibrillation (23) or with a combination of such conditions, were treated with warfarin. The cumulative period of exposure to embolic events during follow-up was 814 years in the whole population in the absence of anticoagulant treatment and 213 years during treatment.. The rate of new embolic events was 1.6 and 0 for 100 patients-years for the two periods respectively. The difference was not statistically significant. No clinically relevant haemorrhagic complication was seen during treatment.. Oral anticoagulant therapy may be safely given to subgroups of patients with dilated cardiomyopathy at risk of embolic episodes, following empirical guidelines, provided a careful clinical and laboratory monitoring is carried on, even if no definite conclusion may be obtained about the efficacy of this treatment from a non-randomized study with low rates of new embolic events.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cardiomyopathy, Dilated; Chi-Square Distribution; Drug Evaluation; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Warfarin

A 59-year-old male with a mechanical aortic valve taking warfarin presented to hospital with Brown-Séquard syndrome caused by a spontaneous spinal epidural hematoma (SSEH) precipitated by a coughing fit. Guided by a literature review of the risks of administering or withholding anticoagulation in this patient, doctors advised a regimen of warfarin to achieve an international normalized ratio of 1.5 to 2 and dipyridamole (75 mg qid) to protect against thromboembolic complications while minimizing the risk of recurrent SSEH.

Topics: Anticoagulants; Aortic Valve; Dose-Response Relationship, Drug; Embolism; Epidural Space; Exercise; Heart Valve Prosthesis; Hematoma, Epidural, Cranial; Humans; Male; Middle Aged; Risk Factors; Spinal Diseases; Thrombosis; Warfarin

The "association" atrial septal aneurysm and mitral valve prolapse is often asymptomatic with an incidence of about 1% in autopsied adults. Occasionally, however, embolic phenomena can occur. The two-dimensional echocardiography allows an accurate diagnosis of these two cardiac lesions when present. In this paper the Authors report on three patients affected by mitral valve prolapse associated with atrial septal aneurysm, one of whom complicated by a cerebral embolism. Owing to the significant incidence of peripheral or cerebral vascular embolic events in this group of patients, the Authors conclude that long-term anticoagulation therapy is mandatory in all cases, whereas a surgical repair could be advisable when a previous embolism or interatrial shunting is demonstrated.

Topics: Adult; Echocardiography; Embolism; Female; Heart Aneurysm; Heart Atria; Heart Septum; Humans; Incidence; Intracranial Embolism and Thrombosis; Male; Middle Aged; Mitral Valve Prolapse; Time Factors; Warfarin

A patient with biventricular thrombus formation in dilated cardiomyopathy suffered massive combined systemic and pulmonary embolization shortly after oral anticoagulation was started. Although this can be coincidental, it can also suggest that the basis of a thrombus may dissolve first with any, including oral, anticoagulation. In unusual conditions surgical removal of thrombi in dilated cardiomyopathy may be a safer alternative.

Topics: Adult; Cardiomyopathy, Dilated; Embolism; Female; Heart Diseases; Humans; Pulmonary Embolism; Thrombosis; Warfarin

Paradoxical embolism through a patent foramen ovale is a recognized cause of stroke, but clinical predictors, recurrence rate, and prevention of brain infarcts in patients with patent foramen ovale have not been determined. We reviewed transesophageal echocardiographic records to ascertain echocardiographic predictors and optimal prophylaxis for patent foramen ovale-related infarcts.. A patent foramen ovale was identified in 74 patients during 615 transesophageal echocardiograms by color Doppler or saline contrast during a 60-month period. On the basis of final clinical situation, the patients were divided into the following groups: group 1, infarct with patent foramen ovale a likely cause (n = 16); group 2, infarct with patent foramen ovale an unlikely cause (n = 23); and group 3, no infarct (n = 35). Transesophageal echocardiograms were reviewed to assess patent foramen ovale characteristics and associated cardio-embolic sources without knowledge of clinical details or group assignment. Follow-up after a patent foramen ovale-related infarct was obtained by telephone or written correspondence in 15 of 16 group 1 patients.. Atrial septal aneurysms were more common in group 1 (38%) compared with group 2 (10%) and group 3 (8%) (P = .02). Contrast right-to-left shunting occurred in 88% of group 1 (P = .06) and 86% of group 2 (P = .07) compared with 60% of group 3. Prevention of recurrence in subjects with presumed patent foramen ovale-related brain infarcts varied. Aspirin was usually chosen after initial brain ischemia. Warfarin and patent foramen ovale closure were usually reserved for subjects with symptoms of brain ischemia while taking aspirin or those who required warfarin or cardiac surgery for other indications. No recurrent infarcts occurred in 15 patients during a mean follow-up period of 28 months.. Atrial septal aneurysm and right-to-left shunt may be predictive of a patent foramen ovale that predisposes a patient to stroke. Aspirin may provide sufficient infarct prophylaxis after initial ischemia. Warfarin and surgical correction should likely be reserved for those in whom aspirin is not effective or those who require warfarin or cardiac surgery for other reasons until prospective studies are available.

Topics: Adult; Aged; Aspirin; Cerebral Infarction; Cerebrovascular Disorders; Echocardiography, Transesophageal; Embolism; Female; Heart Aneurysm; Heart Diseases; Heart Septal Defects, Atrial; Heart Septum; Humans; Male; Middle Aged; Recurrence; Warfarin

The underlying embolic material detected by transcranial Doppler ultrasound in patients with prosthetic heart valves remains unknown. We undertook this study to evaluate the relation between the number of Doppler emboli signals and the activity of the coagulation system.. Patients with various types of prosthetic valves (n = 120) and patients in atrial fibrillation (n = 20) were monitored for 30 minutes using transcranial Doppler with a 2-MHz probe. The plasma concentrations of cross-linked D-dimer, antithrombin-III, and thrombin-antithrombin III complex were measured.. No correlation between the levels of any of the hematologic parameters and the number of emboli was demonstrated in the studied groups. The D-dimer levels were significantly higher in patients with mechanical prosthetic valves with an international normalized ratio under 2.0 compared with those with an international normalized ratio between 2 and 3.5 or above 3.5, and in patients with Medtronic-Hall versus Björk-Shiley or Carpentier-Edwards valve prostheses.. The lack of correlation between the activity of the coagulation system and the number of Doppler emboli in patients with prosthetic valves suggests that the underlying embolic material in these patients is not thrombotic. Our results also suggest that an increase of the anticoagulation intensity to an international normalized ratio above 3.5 does not result in a further decrease of the activity of the unstimulated coagulation system in patients with mechanical prosthetic valves.

Topics: Adult; Aged; Antithrombin III; Atrial Fibrillation; Bioprosthesis; Blood Coagulation; Cerebral Arteries; Echoencephalography; Embolism; Fibrin Fibrinogen Degradation Products; Heart Valve Prosthesis; Humans; Middle Aged; Peptide Hydrolases; Prosthesis Design; Thromboembolism; Warfarin

Topics: Aspirin; Drug Therapy, Combination; Embolism; Heart Valve Prosthesis; Hemorrhage; Humans; Warfarin

We report 4 cases of Trousseau's syndrome, in which spontaneous recurrent or migratory venous thromboses, arterial emboli caused by nonbacterial thrombotic endocarditis, or both, develop in a patient with a recognized or occult malignant tumor. The clinical course of 3 of the patients emphasizes a key point: The occurrence for no known reason of thromboses preventable by anticoagulation therapy with heparin but not with warfarin sodium should alert a physician to focus diagnostic efforts on uncovering an underlying malignant lesion. Thromboses may occur months to years before the tumor is discovered, and a thorough negative initial examination does not obviate the need for a continuing search. Patients with Trousseau's syndrome have persistent low-grade intravascular coagulation, and therapy with heparin should be continued indefinitely. Stopping heparin therapy for even a day may permit a new thrombosis to develop. Immunostaining a biopsy specimen from 1 patient provided evidence that 2 properties of a neoplastic lesion are required for the syndrome to develop: The malignant cells express surface membrane tissue factor, and structural features of the tumor permit the malignant cells or vesicles it sheds to be exposed to circulating blood.

Topics: Adult; Embolism; Female; Heparin; Humans; Male; Middle Aged; Neoplasms; Recurrence; Syndrome; Thrombosis; Warfarin

Topics: Aged; Aortic Aneurysm, Abdominal; Arteriosclerosis; Cholesterol; Embolism; Humans; Male; Skin; Toes; Warfarin

Topics: Age Factors; Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Embolism; Humans; Risk Factors; Warfarin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Embolism; Hospitals, Public; Humans; Inpatients; Medical Audit; Middle Aged; New Zealand; Prospective Studies; Warfarin

Topics: Acute Disease; Acyclovir; Administration, Oral; Antibodies, Viral; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Embolism; Humans; Immunoassay; Infectious Mononucleosis; National Institutes of Health (U.S.); Simplexvirus; United States; Warfarin

Taking a precise history from a patient who presents with a "bruised" toe in the absence of trauma requires sharp assessment skills and an investigative nature. Looking beyond the obvious in an otherwise healthy appearing individual calls for knowledge of many different disease processes including blue toe syndrome. Rapid identification, proper diagnosis, and correct medical and nursing management are essential for a positive outcome.

Topics: Embolism; Humans; Leg; Nursing Assessment; Patient Discharge; Tomography, X-Ray Computed; Warfarin

Topics: Embolism; Hemorrhage; Humans; Quality of Life; Thrombophlebitis; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Dipyridamole; Embolism; Humans; Warfarin

Embolic occlusion of lower extremity arteries caused by hyperthyroidism-induced atrial fibrillation occurs rarely. Severe end organ damage may be prevented by aggressive medical and surgical intervention. Subtle signs of hyperthyroidism should be sought when arterial occlusion and atrial dysrhythmia are discovered. About 25% of thyrotoxic patients have atrial fibrillation, and up to 40% of this subgroup have systemic emboli; thus, 3% to 10% of all thyrotoxic patients may have systemic emboli. This estimation supports the recommendation for anticoagulation in all hyperthyroid individuals with atrial fibrillation.

Topics: Adult; Atrial Fibrillation; Embolism; Female; Femoral Artery; Humans; Quinidine; Syndrome; Thyrotoxicosis; Warfarin

To determine whether two-dimensional echocardiography can identify patients with left ventricular thrombus after myocardial infarction who are prone to embolism, clinical and echocardiographic variables in 541 patients with a first infarction between 1979 and 1983 were studied prospectively. The first echocardiogram showed definite thrombus in 115 patients (Group 1, 21%) and no thrombus in 426 (Group 2, control). In Group 1, 27 patients (23%) had clinical evidence of systemic embolism related to the thrombus before referral (Group 1a) and 88 did not (Group 1b); these two groups were similar in age, gender and infarct location, but more Group 1a patients were within 1 month of the acute infarction. In both Groups 1a and 1b, the thrombus was found in apical views over asynergic zones, with no difference (p greater than 0.05) between the two groups in the size (average area from two views being 5.3 versus 4.5 cm2), type (protruding in apical views 30% versus 27%), location (apical 83% versus 86%; septal 11% versus 11%; posterior 4% versus 2%), extent of asynergy (31% versus 33%) and ejection fraction (33% versus 34%). However, the frequency of anticoagulant therapy was less (26% versus 63%, p less than 0.005), adjacent hyperkinesia greater (100% versus 49%, p less than 0.005) and thrombus mobility greater (81% versus 19%, p less than 0.005) in Group 1a than in Group 1b. Serial echocardiograms revealed a decreased size of the thrombus by 6 months in both Groups 1a and 1b, and little or no trace in 85% by 24 months. Thus, ventricular thrombus size, location and protrusion in apical views on echocardiography did not correlate with embolism. In contrast, thrombus mobility, the presence of adjacent hyperkinesia and thrombus protrusion assessed in multiple views appeared to be strong discriminators of thrombus prone to embolism. These echocardiographic features might provide a guide for the duration of anticoagulant therapy.

Topics: Adult; Aged; Echocardiography; Electrocardiography; Embolism; Female; Follow-Up Studies; Heart Diseases; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Thrombosis; Tomography, X-Ray Computed; Warfarin

One thousand four Medtronic Hall valves (601 mitral, 398 aortic, and five tricuspid) were implanted in 847 patients between December 1979 and June 1987. Total experience at the end of June 1987 was 2,640 patient-years of follow-up. Prothrombin time ratios were reviewed for all patients (16,866 observations), and these ratios were found to be therapeutically low (median international normalized ratio, 2.6) and highly variable (lower 10th percentile, 1.6; upper 10th percentile, 3.9). During the follow-up period, there were no valvular thromboses; the 95% confidence limit for the risk of thrombosis (0.14 per 100 patient-years) is below that reported for other mechanical prostheses. Sixty percent of all thromboembolic events left no residual deficit, and 75% of all bleeding events did not require treatment. Only 11% of thromboembolic events and 7% of bleeding events were fatal. The linearized rate of fatal bleeding was 0.2% per year, and the linearized rate of moderate to severe bleeding was 0.5% per year. Five-year actuarial embolic-free rates were 92%, 84%, and 83% for aortic, mitral, and double valves, respectively. The low risk of valvular thrombosis and of serious thromboembolic events in the Medtronic Hall valve, regardless of the range and variability of anticoagulation, offers greater patient safety than other mechanical prostheses, provides a credible alternative to bioprostheses, and may be particularly relevant to third-world populations.

Topics: Actuarial Analysis; Embolism; Follow-Up Studies; Heart Valve Prosthesis; Heart Valves; Humans; Middle Aged; Postoperative Complications; Thromboembolism; Thrombosis; Warfarin

Although left ventricular thrombi are associated with an increased embolic risk in the first few weeks after acute myocardial infarction, the long-term risk remains undefined. To ascertain the incidence of strictly defined systemic emboli, we followed 85 patients with echocardiographically documented left ventricular thrombi. At the time of the entry echocardiogram, most patients (n = 57) had remote myocardial infarction, while 19 had recent (less than 1 month) infarction, and nine had idiopathic cardiomyopathy. Because of the difficulty in classifying events as embolic in patients with advanced atherosclerosis, a matched control group of 91 patients without thrombi was also studied. The thrombus and control groups were similar with regard to recent myocardial infarction, remote infarction, anterior infarction, ejection fraction, atrial fibrillation, echocardiographic referral for source of emboli, and warfarin therapy. During a mean follow-up of 22 months after echocardiography, embolic events occurred in 13% (11 of 85) of patients with thrombi compared with 2% (two of 91) control patients (p less than .01). The actuarial probability of being embolus free at 2 years after echocardiography was 86% in patients with thrombi compared with 97% in control patients (p less than .01). All embolic events occurred greater than 1 month after myocardial infarction (range 1 to 96 months). The only clinical or echocardiographic features predictive of embolization were protrusion and mobility of thrombus (both p less than .02). We conclude that the incidence of embolic events is definitely increased in patients with left ventricular thrombi compared with control subjects during long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Echocardiography; Embolism; Follow-Up Studies; Heart Diseases; Humans; Middle Aged; Prospective Studies; Risk; Thrombosis; Time Factors; Warfarin

The "purple toes syndrome" is a rare complication of oral anticoagulant therapy. Four patients who presented with "purple toes syndrome" several weeks after warfarin therapy was initiated are described. The diagnosis of cholesterol microembolization was made by biopsy in three cases. Malignant hypertension and renal failure developed in two patients who died within three to six months of onset of purple toes. Postmortem examination in one of these patients showed widespread cholesterol microembolization. Renal failure has not developed in the other two patients, who are doing well. These biopsy and autopsy results suggest that the warfarin-related "purple toes syndrome" is due to cholesterol microembolization.

Topics: Aged; Arteriosclerosis; Cholesterol; Color; Embolism; Female; Humans; Male; Middle Aged; Regional Blood Flow; Syndrome; Toes; Warfarin

To determine the necessity of long-term warfarin anticoagulation after St. Jude Medical aortic valve replacement in adults, we evaluated the risks of thromboembolism, valve thrombosis, anticoagulant hemorrhage, and sudden cardiac death in two groups of patients. Group I consisted of 41 patients treated with conventional long-term warfarin therapy. Forty-two patients in Group II were treated primarily with antiplatelet therapy (aspirin, dipyridamole, or both); 17 of these patients received warfarin for a short time postoperatively and seven others received it intermittently during the study period. The groups were similar with respect to age, sex, associated cardiovascular disease, and length of follow-up (mean 29 months per patient). In the warfarin-treated group, three late sudden deaths occurred, one of which was preceded by a cerebrovascular accident, for a cardiac mortality of 2.7% per patient-year. There were eight major nonfatal complications (7.3% per patient-year), of which four were hemorrhagic and four embolic. In Group II, there was one sudden cardiac death (1.1% per patient-year) and four major complications occurred (3.2% per patient-year). Two of the complications were embolic and two were episodes of valve thrombosis, both necessitating reoperation. Although the incidence of serious morbidity in the warfarin-treated group was twice that of patients treated with antiplatelet therapy, there were no statistically significant differences in the rates of sudden death or major complications. These data suggest that antiplatelet therapy may be as effective as warfarin in preventing embolism from the St. Jude Medical valve in the aortic position. Valve thrombosis occurred in two patients, both receiving antiplatelet therapy (2.2% per patient-year). Whether this type of valve failure can be prevented by warfarin remains in question.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aortic Valve; Aspirin; Cineradiography; Dipyridamole; Echocardiography; Embolism; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Reoperation; Risk; Warfarin

The nature of intracardiac thrombi were studied, which were the clinical underlying conditions, relation to systemic embolism, growth of thrombus and effect of anticoagulant therapy on the size of the thrombi, in 818 patients with mitral valve disease and 1000 patients with myocardial infarction by two-dimensional echocardiography. (1) Common underlying conditions were atrial fibrillation, enlarged left atrial cavity and predominance of mitral stenosis in cases with left atrial thrombi, and apical asynergy and low ejection fraction in cases with ventricular thrombi. The blood stasis should be the major factor in the formation of intracardiac thrombi. In a condition of blood stasis, dynamic intracavitary echoes which may represent erythrocyte aggregation were observed. (2) The incidence of systemic embolism in patients with thrombi was higher than that in patients without thrombi in cardiac disease. (3) The intracardiac thrombi were living. They grew and/or reduced their size spontaneously and sometimes became detached from the cardiac wall in the form of ball thrombi. (4) The effect of anticoagulant therapy on the regression of thrombi depends on its age.

Topics: Adult; Aged; Atrial Fibrillation; Echocardiography; Embolism; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Myocardial Infarction; Stroke Volume; Thrombosis; Warfarin

One hundred eleven patients with 130 emboli treated in nonteaching private hospitals have been evaluated with respect to cause, mortality rate, and amputation rate. For surgically treated patients with balloon embolectomy, the mortality rate was 13.7 percent overall, with a limb salvage rate of 94.5 percent. The operative mortality was 8.3 percent. The mortality for late embolectomy was 3 percent with a limb salvage rate of 100 percent. The most critical factor in predicting mortality was age of the patient, with a significantly higher mortality in patients of advanced years. In this series, a prolonged duration of embolus before embolectomy did not have an adverse effect on the mortality rate.

Topics: Aged; Arm; Arteries; Atrial Fibrillation; Catheterization; Coronary Disease; Embolism; Female; Heparin; Humans; Leg; Male; Warfarin

In the patient described, marked exacerbation of the hypoprothrombinemic response to warfarin coincided with the addition of erythromycin to the drug regimen. A subsequent study in rats provided evidence that erythromycin is capable of increasing the anticoagulant response to single doses of warfarin. On the basis of case findings, preliminary laboratory data, and related clinical data we conclude that the interaction between warfarin and erythromycin is one of potential significance.

Topics: Animals; Drug Interactions; Embolism; Erythromycin; Erythromycin Ethylsuccinate; Female; Humans; Male; Middle Aged; Parotitis; Partial Thromboplastin Time; Prothrombin Time; Rats; Rats, Inbred Strains; Time Factors; Warfarin

Topics: Arrhythmias, Cardiac; Coronary Angiography; Coronary Disease; Embolism; Female; Heart Aneurysm; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Warfarin

One hundred eighty-three patients with cloth-covered valves were studied from 1 1/2 to 8 years after operation, with an average follow-up time of 3 1/2 years. Over the total period, patients taking Coumadin sustained a 4 percent embolic incidence (1.2 per 100 patient-years); those taking aspirin had a 7 percent incidence (2.6 per 100 patient-years); and those taking Persantine had a 43 percent incidence (10 per 100 patient-years). Patients on no regimen of anticoagulation had a 16 percent embolic rate (four per 100 patient-years), whereas another group of patients who stopped anticoagulants after a year incurred a 13 percent embolic incidence in the subsequent 2 years (6.4 per 100 patient-years). These data showed a significantly lowered embolic rate with anticoagulation and suggest that all patients with cloth-covered valves should be taking anticoagulants. That these valves become epithelialized and do not form thrombus after a year was not borne out by this study. Persantine alone is not a satisfactory anticoagulant. Coumadin appears to be the superior anticoagulant, but if careful monitoring of its use is in question or if serious bleeding complications ensue, aspirin may provide satisfactory protection.

Topics: Anticoagulants; Aortic Valve; Aspirin; Connecticut; Dipyridamole; Embolism; Female; Follow-Up Studies; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Postoperative Complications; Warfarin

The case of a 41-year-old male with a history of multiple emboli and short bowel syndrome who was successfully anticoagulated with sodium warfarin is described. The prothrombin times were stabilized in a therapeutic range with warfarin doses of 5.0 mg -7.5 mg daily. The pharmacokinetics of warfarin suggests that absorption is high in the proximal intestine. The successful use of sodium warfarin in the patient substantiates this finding and demonstrates that short bowel does not necessarily preclude the use of warfarin for anticoagulation. It is suggested that patients with short bowel syndrome may be successfully anticoagulated with oral products; however, careful monitoring of each patient's prothrombin time is necessary because of the variability and extent of bowel loss.

Topics: Adult; Embolism; Humans; Intestinal Diseases; Intestines; Male; Postoperative Complications; Time Factors; Warfarin

Topics: Amphotericin B; Atrial Fibrillation; Candidiasis; Digoxin; Embolism; Endocarditis; Female; Flucytosine; Heart Valve Prosthesis; Humans; Middle Aged; Mitral Valve; Warfarin

Topics: Cecum; Colon; Diagnosis, Differential; Embolism; Gastrointestinal Hemorrhage; Hematoma; Humans; Ileum; Intestinal Mucosa; Intestinal Obstruction; Intestine, Small; Male; Mesentery; Middle Aged; Warfarin

Arterial emboli were extracted from 79 patients between 1955 and 1963 with polyethylene catheter suction systems and/or retrograde flushing and from 149 patients between 1963 and 1973 with Fogarty catheters. The Fogarty-era patients were older, had a greater incidence of ischemic heart disease, and presented with a greater degree of preoperative peripheral ischemia. The limb salvage rate of 87 percent after Fogarty catheter embolectomy was not statistically different from the salvage rate of 79 percent after suction catheter embolectomy, but the number of limbs with distal pulses postoperatively was significantly greater after Fogarty treatment, 64 vs. 42 percent. Delay in treatment and the presence of prior occlusive vascular disease adversely affected results in both eras. The in-hospital embolic recurrences occurred in 9 percent of the patients anticoagulated postoperatively and in 31 percent of those not anticoagulated. Heparin and warfarin were equally effective in preventing recurrences, but wound complications were seen in 33 percent of the heparinized patients, compared with 7 percent of those receiving warfarin and 4 percent of those not anticoagulated.

Topics: Aged; Aortic Diseases; Arm; Catheterization; Embolism; Femoral Artery; Follow-Up Studies; Gangrene; Heparin; Humans; Iliac Artery; Ischemia; Leg; Popliteal Artery; Postoperative Care; Recurrence; Warfarin

Topics: Anticoagulants; Blood Coagulation; Catheterization; Clot Retraction; Electric Stimulation; Embolism; Fibrinolysis; Fibrinolytic Agents; Heparin; Humans; Injections, Intravenous; Methods; Phenindione; Pressure; Prothrombin Time; Pulmonary Embolism; Streptokinase; Thrombophlebitis; Thrombosis; Venoms; Warfarin

Topics: Anti-Bacterial Agents; Aortic Valve; Aspergillosis; Bacterial Infections; Calcinosis; Diagnosis, Differential; Embolism; Endocarditis; Furosemide; Heart Auscultation; Heart Valve Prosthesis; Heparin; Humans; Kidney; Lanatosides; Leg; Male; Middle Aged; Morphine; Myocardial Infarction; Myocardium; Oxygen; Postoperative Complications; Renal Artery; Thrombosis; Tooth Extraction; Warfarin

Topics: Angiography; Embolism; Heparin; Humans; Injections, Intravenous; Male; Middle Aged; Renal Artery Obstruction; Warfarin

Topics: Angiography; Atrial Fibrillation; Electrocardiography; Embolism; Heparin; Humans; Male; Mesenteric Arteries; Middle Aged; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Female; Humans; Middle Aged; Renal Artery Obstruction; Rheumatic Heart Disease; Urography; Warfarin

Topics: Adult; Aortic Valve; Embolism; Female; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Infant, Premature; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Adult; Cardiac Catheterization; Embolism; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Phenindione; Prothrombin Time; Warfarin

Topics: Embolism; Heart Valve Prosthesis; Humans; Warfarin

Topics: Acute Disease; Angiography; Anti-Bacterial Agents; Anticoagulants; Embolism; Female; Humans; Middle Aged; Postoperative Care; Renal Artery Obstruction; Urography; Warfarin

Topics: Anticoagulants; Embolism; Humans; Hypertension, Pulmonary; Myocardial Infarction; Phenindione; Renal Artery Obstruction; Rheumatic Heart Disease; Thrombosis; Warfarin

Topics: Atrial Fibrillation; Embolectomy; Embolism; Gastrointestinal Hemorrhage; Heparin; Humans; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Postoperative Care; Postoperative Complications; Preoperative Care; Radiography; Rheumatic Heart Disease; Vascular Surgical Procedures; Warfarin

Topics: Anticoagulants; Coronary Disease; Dicumarol; Embolism; Ethyl Biscoumacetate; Hemorrhage; Humans; Postoperative Complications; Prothrombin Time; Thrombophlebitis; Toxicology; Warfarin

Topics: Angina Pectoris; Anticoagulants; Arteriosclerosis; Blood Coagulation Tests; Drug Therapy; Embolism; Family Practice; General Practice; Myocardial Infarction; Office Management; Prothrombin Time; Rheumatic Heart Disease; Thrombosis; Toxicology; Warfarin

Topics: Acenocoumarol; Adolescent; Angiography; Anticoagulants; Arteriosclerosis Obliterans; Blood Vessels; Child; Drug Therapy; Embolism; Geriatrics; Heparin; Humans; Postoperative Care; Tetralogy of Fallot; Thromboangiitis Obliterans; Thrombosis; Vascular Surgical Procedures; Warfarin