Rivaroxaban has similar safety, efficacy versus warfarin in older and younger nonvalvular afib patients

Rivaroxaban appears to have similar safety and efficacy compared with warfarin in both older and younger patients with nonvalvular atrial fibrillation, although stroke and major bleeding rates were higher in the former group, a new study found.

Researchers from the ROCKET AF trial, which was funded by Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare, performed a prespecified secondary analysis to compare outcomes of rivaroxaban and warfarin treatment in older versus younger patients. Patients were included in ROCKET AF if they had nonvalvular atrial fibrillation and previous stroke, transient ischemic attack, or systemic embolism or at least 2 risk factors for stroke. Patients were randomly assigned to receive adjusted-dose warfarin with a target international normalized ratio of 2.0 to 3.0 or rivaroxaban, 20 mg/d (15 mg/d in those with a creatinine clearance <50 mL/min). The primary study end point was stroke and systemic embolism according to intention to treat. The study results were published online June 3 by Circulation.

ROCKET AF included 14,264 patients, 6,229 of whom (44%) were 75 years of age or older. The median age was 79 years in elderly patients and 66 years in younger patients. The study involved a total of 10,866 patient-years of exposure, over which rates of primary events (2.57% vs. 2.05% per 100 patient-years; P=0.0068) and major bleeding (4.63% vs. 2.74% per 100 patient-years; P<0.0001) were higher in older patients than in younger patients. However, for rivaroxaban versus warfarin, rates of stroke and systemic embolism as well as major bleeding were consistent among older and younger patients. Stroke and systemic embolism occurred among 2.29% of elderly patients taking rivaroxaban and 2.85% of those taking warfarin per 100 patient-years (hazard ratio, 0.80; 95% CI, 0.63 to 1.02), while rates among younger patients were 2.00% versus 2.10% per 100 patient-years (hazard ratio, 0.95; 95% CI, 0.76 to 1.19). Major bleeding rates among elderly patients were 4.86% per 100 patient-years in those taking rivaroxaban and 4.40% per 100 patient-years in those taking warfarin (hazard ratio, 1.11; 95% CI, 0.92 to 1.34), compared with 2.69% versus 2.79% per 100 patient-years in younger patients (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Rates of hemorrhagic stroke were also similar in both younger and older patients.

The authors noted that ROCKET AF might not have lasted long enough to capture the true rates of potential adverse events and that included patients were all at fairly high risk for stroke, among other limitations. However, they wrote, “The main clinical implication of this study is that in elderly patients with nonvalvular [atrial fibrillation] at high risk of stroke, factor Xa inhibition with rivaroxaban is as effective as adjusted-dose anticoagulation with warfarin.”

An accompanying editorial pointed out that “new oral anticoagulants may offer increased convenience for elderly patients, because of their more predictable pharmacologic profiles, a rapid onset of action, a broader therapeutic window, and no specific requirement for routine coagulation monitoring,” in addition to fewer food and drug reactions than warfarin. The authors suggested that existing bleeding risk scores could be improved in the elderly and noted that warfarin is still the preferred therapy in some patients, such as those with mechanical valves or left ventricular thrombi and those in whom the ability to monitor international normalized ratio is helpful. Warfarin is also less expensive, the authors stressed.

“Regardless of the medication chosen, however, older patients must always be treated cautiously due to an increased risk of stroke and bleeding, and additional challenges related to drug interactions,” the editorialists wrote. “As additional data is gathered in this large and higher risk population, our ability to guide optimal use in terms of risk/benefit as well as choose the optimal medication/dosage and mitigate drug interaction, will expand and lead to better care of our older patients. However, while there is no doubt about the benefits of oral anticoagulation in the elderly, focus must be placed on reducing their risk.”