Management and Outcomes of Major Bleeding During Treatment With Dabigatran or Warfarin

Abstract

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...

Ideal Warfarin Dose Adjustment in Cardiac Patients for Safety Inr Outcome.

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Practical aspects of new oral anticoagulant use in atrial fibrillation

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