Most vitamin K antagonists have a long half-life (acenocoumarol, 10 h; warfarin, 36-48 h; phenprocoumon, 120-150 h), Background-The aim of this study was to compare the management and prognosis of major bleeding in patients treated with dabigatran or warfarin. Methods and Results-Two independent investigators reviewed bleeding reports from 1034 individuals with 1121 major bleeds enrolled in 5 phase III trials comparing dabigatran with warfarin in 27 419 patients treated for 6 to 36 months. Patients with major bleeds on dabigatran (n=627 of 16 755) were older, had lower creatinine clearance, and more frequently used aspirin or non-steroid anti-inflammatory agents than those on warfarin (n=407 of 10 002). The 30-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence interval, 0.46-1.01; P=0.057). After adjustment for sex, age, weight, renal function, and concomitant antithrombotic therapy, the pooled odds ratio for 30-day mortality with dabigatran versus warfarin was 0.66 (95% confidence interval, 0.44-1.00; P=0.051). Major bleeds in dabigatran patients were more frequently treated with blood transfusions (423/696, 61%) than bleeds in warfarin patients (175/425, 42%; P<0.001) but less frequently with plasma (dabigatran, 19.8%; warfarin, 30.2%; P<0.001). Patients who experienced a bleed had shorter stays in the intensive care unit if they had previously received dabigatran (mean 1.6 nights) compared with those who had received warfarin (mean 2.7 nights; P=0.01). Conclusions-Patients who experienced major bleeding on dabigatran required more red cell transfusions but received less plasma, required a shorter stay in intensive care, and had a trend to lower mortality compared with those who had major bleeding on warfarin. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.113.002332Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. Received February 28, 2013; accepted September 23, 2013. but their anticoagulant effects can be reversed within 10-20 minutes by prothrombin complex concentrates (PCCs) and within 6-12 h by vitamin K. 4 Dabigatran does not have an antidote but has a half-life of 12-14 h, 5 and withholding the drug for 1-2 days is sufficient to restore hemostasis in most cases of mild to moderate bleeding. In patients with life-threatening bleeding, more rapid restoration of hemostasis might be achieved by the use of hemodialysis to remove the drug, 6-8 activated charcoal to prevent gastrointestinal absorption of recently ingested drug, 9 and the administration of PCCs, 10 activated PCCs, 11 or recombinant activated factor VII (rFVIIa) 12 to enhance thrombin generation. Evidence concerning the efficacy of these approaches is, however, limited to experimental and animal studies and isolated case reports.10,13 Shortening of coagulation time is not always equivalent with restoration of hemostasi...

AimsWe evaluated the effects of dabigatran compared with warfarin in the subgroup of patients with previous symptomatic heart failure (HF) in the RE-LY trial. Methods and resultsRE-LY compared two fixed and blinded doses of dabigatran (110 and 150 mg twice daily) with open-label warfarin in 18 113 patients with AF at increased risk for stroke. Among 4904 patients with HF, annual rates of stroke or systemic embolism (SE) were 1.92% for patients on warfarin compared with 1.90% for dabigatran 110 mg [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.69-1.42] and 1.44% for dabigatran 150 mg (HR 0.75, 95% CI 0.51-1.10). Annual rates of major bleeding were 3.90% for the group on warfarin, compared with 3.26% for dabigatran 110 mg (HR 0.83, 95% CI 0.64-1.09) and 3.10% for dabigatran 150 mg (HR 0.79, 95% CI 0.60-1.03). Rates of intracranial bleeding were significantly lower for both dabigatran dosages compared with warfarin in patients with HF (dabigatran 110 mg vs. warfarin, HR 0.34, 95% CI 0.14-0.80; dabigatran 150 mg vs. warfarin, HR 0.39, 95% CI 0.17-0.89). The relative effects of dabigatran vs. warfarin on the occurrence of stroke or SE and major bleeding were consistent among those with and without HF and those with low (≤40%) or preserved (.40%) LVEF (P interaction not significant). ConclusionsThe overall benefits of dabigatran for stroke/SE prevention, and major and intracranial bleeding, relative to warfarin in the RE-LY trial were consistent in patients with and without HF.--

It is unclear whether thrombophilia causes resistance to anticoagulant therapy. Post hoc analyses of data from RE-COVER, RE-COVER II, and RE-MEDY were performed to compare dabigatran etexilate with warfarin for the treatment and prevention of venous thromboembolism (VTE) in patients with thrombophilia or antiphospholipid antibody syndrome (APS). There were no significant differences in symptomatic VTE/VTE-related deaths between dabigatran etexilate and warfarin in patients with or without thrombophilia. All bleeding event categories were less frequent with dabigatran etexilate than with warfarin, regardless of whether patients had thrombophilia, no thrombophilia, or were not tested. However, these differences did not reach significance in every group. In patients with APS, there was no significant difference in VTE/VTE-related deaths between the two treatment arms. Rates of bleeding events tended to be lower with dabigatran etexilate than with warfarin, reaching statistical significance for any bleeding event. In conclusion, the efficacy and safety of dabigatran etexilate were not significantly affected by the presence of thrombophilia or APS. ClinicalTrials.gov RECOVER IDENTIFIER NCT00291330; RECOVER II IDENTIFIER NCT00680186; RE-MEDY IDENTIFIER NCT00329238.