Efficacy and Safety of Rivaroxaban Compared with Warfarin among Elderly Patients with Nonvalvular Atrial Fibrillation in the ROCKET AF Trial
Background—Nonvalvular atrial fibrillation (AF) is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the ROCKET AF trial. This prespecified secondary analysis compares outcomes in older and younger patients.
Methods and Results—There were 6229 patients (44%) aged ≥75 years with AF and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio 2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double-blind. The primary endpoint was stroke and systemic embolism (SE) by intention-to-treat (ITT). Over 10,866 patient-years, older participants had more primary events (2.57% vs. 2.05%/100 patient-years, P=0.0068) and major bleeding (4.63% vs. 2.74%/100 patient-years, P<0.0001). Stroke/SE rates were consistent among older (2.29% rivaroxaban vs. 2.85% warfarin per 100 patient-years; hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.63-1.02) and younger patients (2.00% vs. 2.10%/100 patient-years; HR 0.95, 95% CI 0.76-1.19, interaction P=0.313), as were major bleeding rates (≥75 years 4.86% rivaroxaban vs. 4.40% warfarin per 100 patient-years; HR 1.11, 95% CI 0.92-1.34; <75 years 2.69% vs. 2.79%/100 patient-years; HR 0.96, 95% CI 0.78-1.19, interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response.
Conclusions—Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly.
Clinical Trial Registration Information—ClinicalTrials.gov; Unique Identifier: NCT00403767.
- Received July 9, 2013.
- Revision received April 23, 2014.
- Accepted April 28, 2014.