August 10th, 2011
Rivaroxaban Compared with Warfarin in 14,000 AF Patients
In ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), researchers tested rivaroxaban (20 mg/day) against warfarin in 14,264 patients with nonvalvular atrial fibrillation (AF). The results of the trial, which were first presented last November at the American Heart Association meeting, have now been published in the New England Journal of Medicine.
The primary per-protocol analysis demonstrated that rivaroxaban was noninferior to warfarin: the rate of stroke or systemic embolism was 1.7% per year in the rivaroxaban group compared with 2.2% per year in the warfarin group (HR for rivaroxaban: 0.79, CI 0.66-0.96, p<0.001 for noninferiority).
The intention-to-treat analysis also demonstrated noninferiority but did not demonstrate superiority: the event rate was 2.1% per year with rivaroxaban compared with 2.4% per year with warfarin (HR 0.88, CI 0.74-1.03, p<0.001 for noninferiority, p=0.12 for superiority).
The ROCKET AF investigators write that the difference between the two analyses “reflects the fact that among patients who discontinued therapy before the conclusion of the trial, no significant difference in outcomes would have been anticipated, and none was seen.”
The rate of major and nonmajor clinically relevant bleeding did not differ significantly between the two groups, but rivaroxaban was associated with significant reductions in intracranial hemorrhage and fatal bleeds:
- Major and nonmajor clinically relevant bleeding: 14.9% per year with rivaroxaban and 14.5% per year with warfarin, HR 1.03, CI 0.96-1.11, p=0.44)
- Intracranial hemorrhage: 0.5% versus 0.7%, p=0.02
- Fatal bleeding: 0.2% versus 0.5%, p=0.003
In an accompanying editorial, Gregory del Zoppo and Misha Eliasziw note that treatment with both rivaroxaban in ROCKET AF and dabigatran in RE-LY resulted in a lower rate of intracranial hemorrhage compared with warfarin, although no difference in overall major bleeding events was observed in either trial. They speculate that cerebral vascular beds may “have protective features that are more apparent at the doses of either of the new agents tested.”
The editorialists conclude that “oral alternatives to warfarin have arrived,” but hedge their enthusiasm by noting that “comparisons seem to depend on how easily the patient can be treated with warfarin.”