Patients with atrial fibrillation who use anticoagulants and have a history of gastrointestinal bleeding may be at higher risk for subsequent major gastrointestinal bleeding, but not all-cause mortality or stroke, according to study results published in the American Heart Journal.

In this study, researchers used data from the Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation trial (ARISTOTLE; identifier: NCT00412984), a double-blind randomized controlled trial in which 18,201 patients with atrial fibrillation and ≥1 additional risk factor for stroke were enrolled.

A total of 784 participants (4.3%) had a history of gastrointestinal bleeding and (321 and 463 patients had lower and upper bleeding, respectively). Patients with gastrointestinal bleeding were older and more likely to have impaired renal function and ≥1 comorbidities, including anemia, dyspepsia, and peripheral or coronary artery disease. At baseline, 215 patients (27%) had experienced gastrointestinal bleeding within 1 year.

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During the study, major gastrointestinal bleeding occurred more frequently in patients with vs without a history of gastrointestinal bleeding (lower bleeding: adjusted hazard ratio [aHR], 1.72; 95% CI, 0.86-3.42; upper bleeding: aHR, 3.13, 95% CI, 1.97-4.96). This association with major gastrointestinal bleeding was more prevalent in patients who experienced gastrointestinal bleeding within vs over 1 year before study start (lower bleeding: aHR, 2.58, 95% CI, 0.95-7.01; upper bleeding: aHR, 5.16, 95% CI, 2.66-10.0). No associations between a history of gastrointestinal bleeding and stroke or all-cause death were identified. A history of gastrointestinal bleeding was not found to affect the relative risk of apixaban vs warfarin for stroke, major hemorrhage, or all-cause death.

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Study limitations include a lack of randomization. “Although this risk increase may change calculations regarding the net benefit of anticoagulation therapy in general, we found no evidence that a history of [gastrointestinal] bleeding would substantially modify what is already known about the superiority of apixaban as compared with warfarin in the relative risks for important clinical outcomes such as stroke or systemic embolism, major bleeding, and all-cause death,” concluded the study authors.

 Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Garcia DA, Fisher DA, Mulder H, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial [published online October 31, 2019]. Am Heart J. doi: 10.1016/j.ahj.2019.10.013