Another Warfarin Replacement on Horizon

Just as Boehringer Ingelheim begins marketing dabigatran (Pradaxa®) as a replacement for warfarin, a competitor drug may be on the horizon. As reported at the American Heart Association (AHA) meetings in November, rivaroxaban, an oral drug factor Xa inhibitor, is as effective as warfarin at preventing stroke and blood clots in patients with nonvalvular atrial fibrillation.

The ROCKET AF study (Stroke Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared With Warfarin in Patients with Nonvalvular Atrial Fibrillation) looked at more than 14,000 patients with atrial fibrillation. Patients were randomized to warfarin or rivaroxaban (20 mg/day). The time in therapeutic range for warfarin was 57.8%. With a primary endpoint of stroke and non-CNS systemic embolism, rivaroxaban was associated with a rate of 1.71 events per 100 patient-years vs 2.16 for warfarin (P = 0.015 for superiority and P < 0.001 for non-inferiority). On an intention to treat (ITT) basis, event rates were 2.12 for rivaroxaban vs 2.42 for warfarin (P = 0.117). There were 55 intracranial bleeds with rivaroxaban compared with 84 with warfarin (P = 0.019). Rivaroxiban also showed numerically fewer MIs (0.91 vs 1.12 per 100 person-years; P = 0.12). All-cause mortality was 1.87 in the rivaroxaban group vs 2.21 in the warfarin group (P = 0.073). In the ITT analysis, mortality was 4.52 vs 4.91 (P = 0.152), respectively.

This study (presented at the American Heart Association Scientific Sessions; Chicago, IL; Nov. 15, 2010) was the seventh Phase III trial in the development of rivaroxaban, with other studies evaluating the drug for prevention and treatment of venous thromboembolism, indications that Bayer and Johnson & Johnson have already filed with the FDA. It is also expected that a new drug application will be filed soon for the prevention of stroke in patients with nonvalvular atrial fibrillation. Like dabigatran, rivaroxaban requires no monitoring and has few drug interactions. Rivaroxaban has the advantage of being dosed once a day compared to twice-daily dosing for dabigatran.