Risk of Bleeding With Dabigatran in Atrial Fibrillation

Study Questions:

What is the risk of bleeding among Medicare patients with atrial fibrillation (AF) taking dabigatran versus warfarin?


A random 5% Medicare sample was explored as a retrospective cohort study of patients with newly diagnosed AF who were initiated on dabigatran or warfarin between 2010 and 2011. Patients were followed until medication discontinuation, death, or the end of 2011. Bleeding events were categorized as major or minor events based on the location of the bleed. Propensity score matching and Cox proportional hazard regression were used to evaluate the risk of bleeding in the two groups. Subgroups at high risk for bleeding were also explored.


Dabigatran was associated with a higher risk of overall bleeding relative to warfarin in the cohort study (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.20-1.41). Dabigatran was also associated with a higher risk of major bleeding (HR, 1.58; 95% CI, 1.36-1.83) and gastrointestinal bleeding (HR, 1.85; 95% CI, 1.64-2.07) than warfarin. The risk of intracranial hemorrhage was significantly lower in dabigatran versus warfarin (HR, 0.32; 95% CI, 0.20-0.50). Dabigatran was associated with a higher bleeding risk across all subgroups analyzed, especially for African Americans and patients with chronic kidney disease.


The authors concluded that while dabigatran’s use is associated with a significantly reduced risk of intracranial hemorrhage, it is associated with a significantly elevated risk of overall, major, and gastrointestinal bleeding compared to warfarin in elderly AF patients.


This retrospective cohort study adds mounting evidence to the claim that dabigatran’s use in elderly patients is associated with an increased risk of extracranial bleeding. This study is consistent with a post-hoc subgroup analysis of the RE-LY trial where older patients (ages ≥75 years) had higher rates of extracranial bleeding when treated with dabigatran 150 mg. This same risk has not been demonstrated with the other direct oral anticoagulants (particularly rivaroxaban and apixaban). Still, dabigatran’s use consistently demonstrates a significantly reduced risk of intracranial hemorrhage, the most feared complication of systemic anticoagulation. Clinicians should be forthright with their patients when discussing the risks and benefits of using warfarin versus each of the direct oral anticoagulants for stroke prevention in AF.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents

Keywords: Stroke, Intracranial Hemorrhages, beta-Alanine, Anticoagulants, African Americans, Benzimidazoles, Warfarin, Atrial Fibrillation, Confidence Intervals, Risk Assessment, Medicare, Renal Insufficiency, Chronic

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