Predictors of Gastrointestinal Bleeding Among Patients with Atrial Fibrillation After Initiating Dabigatran Therapy

More than 460,000 individuals in the United States are newly diagnosed with atrial fibrillation (AF) annually.1 Thought to affect 3 million Americans, AF is only increasing in prevalence and incidence as the population ages.1,2 Moreover, the average rate of ischemic stroke among patients with nonvalvular AF is approximately 5% per year, which is thought to be 2–7 times that of the general United States population.3 Use of anticoagulation in patients with AF is recommended to prevent thromboembolic stroke and systemic embolism.4 However, use of anticoagulants can lead to an increased risk of bleeding, and, in particular, gastrointestinal (GI) bleeding.5,6 GI bleeding alone is significantly associated with morbidity and mortality; mortality from GI bleeding has ranged from 1–13%, depending on the location in the GI tract.7–9 Until recently, warfarin was the only U.S. Food and Drug Administration (FDA)-approved anticoagulant for the prevention of stroke in patients with AF; in October 2010, approval of dabigatran for this indication provided an additional option.4,10–12 Despite demonstrated advantages over warfarin regarding risk of stroke, systemic embolism, and intracranial bleeding events, dabigatran has been shown to lead to an increased risk of GI bleeding in the major clinical trial used for FDA approval and recent observational studies in clinical practice, with overall rates of GI bleeding ranging from 1–6%.13–17 Although knowledge about the increased risk of GI bleeding in patients receiving anticoagulants has expanded, the literature on the risk factors associated with GI bleeding in these patients has been restricted to therapy settings where alternatives to warfarin were not available.5 Little is known regarding demographic and clinical characteristics that lead to higher risks of GI bleeding among patients receiving dabigatran, especially among patients in real-world practice. The ability to better understand patients who are at increased risk of GI bleeding could help clinicians to better identify appropriate patients for dabigatran use, especially given its increased risk of GI bleeding above and beyond warfarin. In addition, among patients who do experience a GI bleed, restarting anticoagulation may still be necessary to prevent stroke after recovering from the bleed, particularly among patients at high stroke risk.5,18 However, little is known regarding anticoagulant treatment patterns after a GI bleed in dabigatran users in clinical practice, and particularly whether these patients persist on any anticoagulation therapy. Therefore, the goal of this study was to identify demographic and clinical risk factors associated with GI bleeding among a large cohort of patients with AF who initiated dabigatran therapy for stroke prevention, and to describe patterns of subsequent anticoagulant use after the occurrence of the GI bleeding event.