History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.
AIMS: History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. METHODS AND RESULTS: The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. CONCLUSION: In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.
De Caterina, R; Andersson, U; Alexander, JH; Al-Khatib, SM; Bahit, MC; Goto, S; Hanna, M; Held, C; Hohnloser, S; Hylek, EM; Lanas, F; Lopes, RD; López-Sendón, J; Renda, G; Horowitz, J; Granger, CB; Wallentin, L; ARISTOTLE Investigators,
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