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

Study Questions:

What are the management of and outcomes following major bleeding in large phase III trials evaluating the efficacy and safety of dabigatran compared with warfarin?


This was a retrospective analysis in which two independent investigators (not blinded to anticoagulant treatment) reviewed bleeding reports from 1,034 individuals with 1,121 major bleeds enrolled in five phase III trials of populations with atrial fibrillation or venous thromboembolism (RE-LY, RE-COVER, RE-COVER II, RE-MEDY, and RE-SONATE). The comparator in all studies was warfarin, save RE-SONATE, which compared dabigatran with placebo. Eligible patients experienced major bleeding on treatment or within 3 days of temporary or permanent discontinuation of treatment. Comparisons between dabigatran 110 mg and 150 mg twice daily as well as between the combined dabigatran groups and warfarin were performed. The main outcomes were 7- and 30-day mortality, management strategies (transfusions of blood and plasma and vitamin K administration), and length of stay in an intensive care setting.


Compared to patients with major bleeding on warfarin, those with major bleeding on dabigatran were older, had worse renal function, and concomitant treatment with aspirin or a nonsteroidal anti-inflammatory agent. In analyses adjusted for sex, age, weight, renal function, and concomitant antithrombotic therapy, the pooled odds ratio [OR] for 30-day mortality with dabigatran versus warfarin was 0.66 (95% confidence interval [CI], 0.44-1.00; p = 0.051). Adjusted ORs separately for dabigatran 110 mg or dabigatran 150 mg versus warfarin were also not significant at 0.65 (95% CI, 0.38-1.11) and 0.68 (95% CI, 0.42-1.08). Major bleeding in patients taking dabigatran was more frequently treated with blood transfusions (61%) than bleeds in warfarin patients (42%), p < 0.001. Those patients who received dabigatran had shorter stays in the intensive care unit setting, compared to those who were taking warfarin (mean 1.6 nights vs. 2.7 nights, p = 0.01).


Patients who experienced major bleeding on dabigatran, when compared to those who had major bleeding on warfarin, required more red blood cell transfusions and had a trend toward lower mortality and a shorter stay in intensive care.


The authors presented analysis of data pooled from five trials to assess the treatment of bleeding in patients prescribed dabigatran, compared to warfarin. The results offer reassurance about the use of dabigatran, which lacks a specific antidote. Data from this study continue to corroborate the implication that dabigatran is an acceptable alternative to warfarin with a favorable overall safety profile following major bleeding.

Clinical Topics: Anticoagulation Management, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Novel Agents

Keywords: Vitamin K, Warfarin, Venous Thromboembolism, Blood Transfusion, Blood Coagulation, Benzimidazoles, Cardiology, Hemorrhage

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