Major Bleeding in Patients With Atrial Fibrillation Receiving Apixaban or Warfarin in the ARISTOTLE Trial: Predictors, Characteristics, and Clinical Outcomes

Study Questions:

What are the clinical characteristics of patients treated with apixaban for stroke prevention in atrial fibrillation (AF), who experienced major bleeding events?


In the ARISTOTLE trial, apixaban (2.5-5 mg twice daily depending on renal function, age and weight) was compared to warfarin for stroke prevention in 18,140 patients with AF. In this post-hoc analysis, factors associated with major bleeding events were explored.


Major bleeding occurred in 789 patients (4.3% overall), with less bleeding in apixaban-treated patients versus warfarin-treated patients (2.13% per year vs. 3.09% per year; hazard ratio [HR], 0.69; p < 0.001). Bleeding events with a 30-day mortality occurred less often in apixaban-treated patients than warfarin-treated patients (HR, 0.5; p < 0.001). Patients experiencing major bleeding were older, more often had a history of myocardial infarction, prior bleeding, impaired renal function and a fall within the prior year when compared to patients without major bleeding events. Bleeding events most commonly occurred in the gastrointestinal tract (31%), intracranially (22%), and in soft tissues (10%). Apixaban was associated with fewer intracranial hemorrhage events, fewer bleeding events related to trauma, and with fewer soft tissue bleeding events than warfarin.


The authors concluded that apixaban is associated with a significant reduction in major bleeding and fatal bleeding events compared to warfarin therapy when used for stroke prevention in AF.


This post-hoc analysis of the ARISTOTLE trial provides additional evidence in support of apixaban’s safety and effectiveness when used for stroke prevention in AF. In addition to the previously reported reduction in intracranial hemorrhage and overall major bleeding rates, this report describes a reduction in major bleeding events, which result in death within 30 days for patients treated with apixaban as compared to warfarin. It is important to recognize that the ARISTOTLE trial was performed without the availability of a reversal agent for apixaban and with high-quality warfarin management. This report should offer providers additional reassurance about the safety of apixaban when used for stroke prevention in well-selected patients with nonvalvular AF.

Clinical Topics: Anticoagulation Management

Keywords: Myocardial Infarction, Stroke, Intracranial Hemorrhages, Warfarin, Pyrazoles, Gastrointestinal Tract, Pyridones, Hemorrhage

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