The ROCKET AF (Stroke Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared With Warfarin in Patients with Nonvalvular Atrial Fibrillation) trial tested rivaroxaban (20 mg/day) against warfarin in 14,264 patients with atrial fibrillation (AF). The results of the trial, which were first presented last November at the American Heart Association, have now been published in the New England Journal of Medicine.
The primary per protocol analysis demonstrated that rivaroxaban (Xarelto, Johnson & Johnson) was noninferior to warfarin: the rate of stroke or systemic embolism occurred in 1.7% of the rivaroxaban group compared with 2.2% in the warfarin group (HR for rivaroxaban: 0.70, CI 0.66-0.96, p<0.001 for noninferiority).
The intention-to-treat analysis also demonstrated noninferiority but did not demonstrate superiority: an endpoint event occurred in 2.1% of the rivaroxaban group versus 2.4% of the warfarin group (HR o.88, CI 0.74-1.03, p<0.001 for noninferiority, p=0.12 for superiority).
The ROCKET AF investigators wrote 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.”
There was no significant difference in the rate of major and nonmajor clinically relevant bleeding 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% in the rivaroxaban group versus 14.5% in the warfarin group, 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.”
It should be noted that the results of ARISTOTLE with another factor Xa inhibitor, apixaban (Eliquis, Pfizer and Bristol Myers), will be presented at the European Society of Cardiology meeting in Paris on August 28. The trial has attracted a great deal of interest, based on a press release that revealed the main results of the trial.
[…] far more difficult than had been expected. Remember that the ROCKET AF trial had been presented and published with broad approval, but then came under heavy fire from FDA reviewers. It is possible that FDA […]