Abstract 15115: Reduction in Bleeding with Apixaban versus Warfarin is Consistent Across Subgroups and Locations: Insights from the ARISTOTLE Trial

Abstract

Background: While oral anticoagulation is effective at preventing stroke, bleeding complications are common and are a major limitation of treatment. We describe the incidence, location, and severity of bleeding with apixaban and warfarin in the ARISTOTLE trial.

Methods: Major bleeding was defined as overt bleeding with a decrease in hemoglobin of ≥2 g/dl or transfusion of ≥2 units of packed red cells or occurring at a critical site or resulting in death. Bleeding outcomes were assessed in patients who received at least one dose of a study drug and included events through day 2 after the last dose. The number of first, location-specific bleeds and rates per 100 person- years* were determined. P-values to compare rates were derived using Cox regression models.

Results: Major bleeding occurred in 789 patients (4.3%); of which 19 (2.4%) were fatal. Risk factors included older age, prior bleed, prior fall, higher CHADS₂ score, use of an antiplatelet agent or gastric acid suppressant, and renal impairment. Major bleeding was lower with apixaban across all major subgroups. The most frequent sites of bleeding and rates of bleeding are shown in the table. The clinical relevance of the numerical difference in intraocular bleeding is unclear. The rate of major bleeding was reduced 31% with apixaban, and when such bleeding occurred, it was associated with similar (or fewer) adverse consequences: transfusions (apixaban vs warfarin, 48% vs 53%, p=0.24), interventions to stop bleeding (35% vs 38%, p=0.37), and hospitalizations (56% vs 61%, p=0.27).

Conclusions: In ARISTOTLE, factors related to bleeding were consistent with previous reports. Nearly one-third of major bleeds were GI, and most of these occurred in the upper GI tract. The 31% relative risk reduction in major bleeding with apixaban was generally preserved regardless of the subgroup or location.