Risk of events in the 30 days following a major bleed with Apixaban or Warfarin - experiences from the ARISTOTLE trial

Abstract

Purpose: Bleeds during anticoagulation are associated with higher risk of subsequent death and thrombotic events. In the ARISTOTLE trial, apixaban compared to warfarin reduced the risk of stroke, major bleed and death in patients with atrial fibrillation. Patient outcomes were evaluated following major bleeding events. Methods: Major ISTH bleeding was defined as overt bleeding accompanied by a decrease in hemoglobin of ≥2 g/dl or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time-to-event (death, ischemic stroke or MI) was evaluated by Cox regression models. The rate of events was assessed by treatment group during 30 days following a bleed. Results: Major bleeding occurred in 859 individuals (4.7%). Out of 179 patients with intracranial hemorrhage (ICH), 76 (42.5%), and 52 (7.4%) out of the 703 patients with major non-ICH died within 30 days of the bleeding. After a major non-ICH, the risk of death or subsequent stroke or MI at 30 days was increased roughly 12-fold (Table). The risk of death at 30 days following an ICH, was markedly increased, with HR 117.5 (95% CI 88.4-156.2) and the risk of a stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. There was no interaction between randomized treatment and the risk of either death or stroke or MI after a major bleeding event. Conclusions: Major bleeding during oral anticoagulant treatment is associated with a substantially increased risk of subsequent death and thrombotic events, particularly following ICH. The risk is similarly elevated, regardless if the bleeding occurred during treatment with apixaban or warfarin.