Rivaroxaban comparable to warfarin in stroke prevention

December 1, 2010

Rivaroxaban, an oral direct Factor Xa inhibitor given once daily was superior to warfarin in reducing the risk of stroke and non-central nervous system systemic embolism in patients with AF, with comparable rates of bleeding in the pre-specified on-treatment population, according to results from the ROCKET AF study.

Key Points

Also, in a more conservative intent-to-treat population (ITT) analysis, which includes data from patients who were randomly assigned into the trial until its completion, whether or not they completed the full course of therapy or switched to other options, rivaroxaban showed comparable benefits to warfarin.

In the study, rivaroxaban was superior to warfarin for the primary efficacy end point, showing a 21% relative risk reduction (RRR) for stroke and non-CNS systemic embolism in the pre-specified on-treatment population (1.7% vs 2.2%, respectively, P=.015). Also, in the ITT, which followed all patients randomly assigned in the trial until its completion, whether or not they completed the full course of therapy or switched to other options, rivaroxaban showed comparable benefits to warfarin (2.1% vs 2.4%, P<.001 for non-inferiority). This result indicates that the treatment benefits compared to warfarin were sustained as long as the patients received rivaroxaban.

Formulary Editorial Advisor Craig Coleman, PharmD, associate professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, and co-director and methods chief, UCONN/Hartford Hospital, shared a similar viewpoint. "Not only is rivoroxaban an efficacious drug for stroke prevention in those with atrial fibrillation, it also can be administered once daily, doesn't require INR monitoring, and does not appear to carry any significant increased bleeding risk compared to warfarin," he said. "In fact, rivaroxaban appears to have a lower risk of intracranial bleeding, critical organ bleeding, and bleeding-related death as compared to warfarin."

For the principal safety measure, rivaroxaban showed similar rates of major and non-major clinically relevant bleeding events, compared to warfarin (14.9% vs 14.5%, P=.442). Rates of major bleeding were also comparable between rivaroxaban and warfarin (3.6% vs 3.5%, P=.576). Patients treated with rivaroxaban had fewer intracranial hemorrhages (0.5% vs 0.7%, P=.019), critical organ bleeds (0.8% vs 1.2%, P=.007), and bleeding-related deaths (0.2% vs 0.5%, P =.003) compared to those treated with warfarin, but showed increased rates of hemoglobin/hematocrit drop (2.8% vs 2.3%, P=.019) and transfusions (1.7% vs 1.3%, P=.044), compared to warfarin. The frequency of abnormal laboratory values of liver function was balanced between the treatment groups. Rivaroxaban had similar rates of discontinuation due to adverse events compared to warfarin, and did not require routine laboratory coagulation monitoring.

Rivaroxaban-treated patients had numerically fewer myocardial infarctions (0.9% vs 1.1%, P=.121), and an observed reduction in rates of all-cause mortality compared to warfarin (1.9% vs 2.2%, P=.073), though these results were not statistically significantly different.

"Importantly, there were no liver enzyme elevations noted," added Dr Mahaffey, who is also co-director, Cardiovascular Research, and director, Clinical Events Classification (CEC) Group, Duke Clinical Research Institute.

Harold L. Karpman, MD, clinical professor of medicine, David Geffen School of Medicine at UCLA, Cardiovascular Medical Group, Beverly Hills, Calif., said: "Strokes occurring in patients with atrial fibrillation occur because clots form in the left atriums of these patients afflicted and, as was clearly pointed out, these death-dealing clots occur less frequently in patients given the new drug as well in those patients receiving Coumadin.

"However, patients receiving Coumadin require frequent blood monitoring and patients given the new drug do not require blood monitoring-to evaluate the prothrombin times-to be performed at all," Dr Karpman added. "The need to receive frequent prothrombin time blood tests is a great inconvenience and often patients are not compliant because of this, which therefore increases the possibilities of developing uncontrolled bleeding and/or more aggressive clotting, which may lead to strokes and other embolic events."

Patients in the trial were at moderate or high risk for future stroke or systemic embolism and much higher risk than previous trials, said Dr Mahaffey.