Abstract 148: Efficacy and Safety of Rivaroxaban Compared with Warfarin Among Elderly Patients with Nonvalvular Atrial Fibrillation in the ROCKET-AF Trial

Abstract

Background: Nonvalvular atrial fibrillation (AF) affects 5-10% of people over 75 years of age, in whom the risk of thromboembolism is higher than in younger individuals. Although warfarin protects against ischemic stroke, many patients cannot sustain treatment because of bleeding, drug interactions and coagulation monitoring. The oral Factor Xa inhibitor, rivaroxaban, displayed noninferior efficacy and safety as an alternative anticoagulant in the ROCKET-AF trial (median age 73 years). This analysis compares these treatments in patients >75 years. Methods: The ROCKET-AF trial (n=14,264) included 6,229 patients >75 years of age with AF and at least 1 additional stroke risk factor randomized to adjusted-dose warfarin (target INR 2.0-3.0) or fixed-dose rivaroxaban (20 mg daily; 15 mg daily if baseline creatinine clearance <50 ml/min), double-blind. The primary endpoint was all strokes (ischemic or hemorrhagic) and systemic embolism analyzed during the on-treatment period and according to intention-to-treat (ITT). Results: Compared to younger patients, those ≥75 years at baseline had a mean CHADS 2 score of 3.7 vs. 3.3, 46 vs. 35% were female, and 42 vs. 65% had prior stroke/TIA. During 9,247 patient-years exposure, 429 stroke or systemic embolic events occurred among patients >75 years old. Long-term tolerability was similar between treatments; 59.4% of patients on warfarin (W) and 59.3% on rivaroxaban (R) completed the trial taking assigned treatment, compared with 69.9 and 68.7% in younger patients. The mean INR in the warfarin group (2.44, SD=0.86) was within target range for 56.9% (SD=21.6) of follow-up, compared to 53.9% (SD=20.9) in younger patients. The table compares annualized event rates for patients <75 and >75 years of age at entry. The on-treatment thromboembolism rates of 1.78 vs. 2.65%/year with rivaroxaban and warfarin, respectively (HR 0.67; 95% CI 0.51-0.89) were not much higher than in younger patients. Older patients had higher rates of (mostly non-major) clinically relevant bleeding (interaction p =0.009), but rates with warfarin and rivaroxaban were comparable. Conclusions: In elderly, high-risk patients with AF, once-daily oral rivaroxaban without coagulation monitoring or dose adjustment performed favorably compared to adjusted-dose warfarin as it did in the overall ROCKET-AF population. 1