Bleeding Risk in Atrial Fibrillation Patients: the Amadeus Study

ABSTRACT BACKGROUND: To assess the impact of combination antithrombotic therapy on stroke and bleeding risk compared to anticoagulation alone in atrial fibrillation (AF) patients. METHODS: Post-hoc analysis of 4576 AF patients [mean (SD) age 70.1 (9.1) years, 66.5% men] enrolled in the AMADEUS trial, randomised to receive either subcutaneous idraparinux (2.5mg weekly, n=2283) or dose-adjusted vitamin K antagonists (VKAs) (INR 2.0-3.0, n=2293). Of these, 848 (18.5%) patients used antiplatelet therapy (aspirin, clopidogrel, ticlopidine, etc) in addition to anticoagulation (combination antithrombotic therapy). RESULTS: 572 (15.3% per year) clinically relevant and 103 (2.6% per year) major bleeds occurred. Patients on combination antithrombotic therapy had 2.3 to 2.5-fold increased risk of clinically relevant bleeds and major bleeds, respectively, compared to those on anticoagulation alone. Multivariate analyses [HR, (95% CI)] revealed that the risk of clinically relevant bleeding was significantly increased by age 65 to 74 years [1.44 (1.14-1.82)] and ≥75 years [1.59 (1.24-2.04)] (p=0.001), and by combination antithrombotic therapy [2.47 (2.07-2.96); p