Risk of Bleeding With Dabigatran in Atrial Fibrillation

Abstract

IMPORTANCE It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice. OBJECTIVE To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data. DESIGN, SETTING, AND PARTICIPANTS In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011. EXPOSURES Dabigatran users (n = 1302) and warfarin users (n = 8102). MAIN OUTCOMES AND MEASURES We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities. RESULTS Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease. CONCLUSIONS AND RELEVANCE Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Direct oral anticoagulants in atrial fibrillation: can data from randomized clinical trials be safely transferred to the general population? Yes

“…Different findings are reported in a recently published analysis from the Medicare database; the rate of major bleeding is reported to be up to 9.0 % with dabigatran vs 5.9 % with warfarin (HR 1.58, 95 % CI 1.36-1.83) [14]. However, in this cohort, the definition of major bleeding also includes the need for emergency department stay, irrespective of hemoglobin loss or the need for transfusions, and baseline patients characteristics suggest a higher risk population treated with dabigatran (mean age 75 years, 33 % chronic kidney disease, and 29 % with seven or more comorbidities [14]). …”

“…In a recent study, using nationwide Danish prescription and patient registries, the highest bleeding rates in a population of AF patients are seen with vitamin K antagonists-naïve warfarin initiators, and no difference in overall bleeding rates is detected between warfarin experienced patients and dabigatran patients [13]. Different findings are reported in a recently published analysis from the Medicare database; the rate of major bleeding is reported to be up to 9.0 % with dabigatran vs 5.9 % with warfarin (HR 1.58, 95 % CI 1.36-1.83) [14]. However, in this cohort, the definition of major bleeding also includes the need for emergency department stay, irrespective of hemoglobin loss or the need for transfusions, and baseline patients characteristics suggest a higher risk population treated with dabigatran (mean age 75 years, 33 % chronic kidney disease, and 29 % with seven or more comorbidities [14]).…”

Novel Anticoagulants in Atrial Fibrillation: A Primer for the Primary Physician

“…44 While the RE-LY study outlines the bleeding risk of warfarin compared with dabigatran within the close follow-up of a clinical trial, a recent article looking at bleeding risk between these drugs with "real life" use should be highlighted. 17,45 In essence this is a retrospective look at a random sampling of medicare beneficiaries over a 1-year period with atrial fibrillation who were prescribed either of these medications. Among dabigatran users (n ϭ 1302) and warfarin users (n ϭ 8102), risk of both major and minor bleeding was higher for dabigatran.…”

Clinical Benefit of American College of Chest Physicians Versus European Society of Cardiology Guidelines for Stroke Prophylaxis in Atrial Fibrillation

“…As compared to warfarin, novel anticoagulants have lower risks of intracranial hemorrhage but risks of extracranial hemorrhage that are equivalent or higher. 3 Whether the benefits of novel anticoagulants outweigh their risks in patients with a CHADS 2 score of 0 is unknown, as low-risk patients were excluded from trials of novel anticoagulants.…”

“…As compared to warfarin, novel anticoagulants have lower risks of intracranial hemorrhage but risks of extracranial hemorrhage that are equivalent or higher. 3 Whether the benefits of novel anticoagulants outweigh their risks in patients with a CHADS 2 score of 0 is unknown, as low-risk patients were excluded from trials of novel anticoagulants.The benefits of anticoagulants in clinical practice are lower than in randomized trials. In our cohort of 65−74-year-old patients with a CHADS 2 score of 0, the stroke equivalents per 100 patient-years were 2.6 with warfarin and 2.9 without warfarin; the difference between these two strategies was not significant.…”