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Rivaroxaban : Advisory Board recommends approval of rivaroxaban in AF by the FDA
The new oral anticoagulant rivaroxaban (Xarelto®), a Xa inhibitor of Bayer HealthCare and Johnson & Johnson, was recently recommended for approval for prevention of stroke by the Food and Drug Administration (FDA) following the ROCKET AF Study presented at the American Heart Association 2010 and published in the New England Journal of Medicine(1).
This double-blind international multicenter trial randomly assigned 14,264 patients with nonvalvular AF to receive rivaroxaban (20mg daily or 15mg in patients with creatinine clearance of 30 to 49ml) or adjusted dose warfarin (target INR 2 to 3). The primary analysis was designed to determine whether rivaroxaban was noninferior in respect to the primary endpoint of stroke or systemic embolism.
The primary endpoint occurred in 188 patients of the rivaroxaban group (1.7%) and in 241 patients of the warfarin group (2.2%) p<0.001 for non-inferiority (hazard ratio for rivaroxaban 0.79;95% CI,0.66 to 0.96). Intention to treat analysis showed that the primary endpoint occurred in 269 patients of the rivaroxaban group (2.1%per year) and in 306 patients of the warfarin group (2.4% per year)
Bleeding: major and nonmajor clinically relevant bleeding occurred in 14.9% (1475 patients) of the rivaroxaban group and in 14.5% (1449 patients) of the warfarin group (P=0.44)
This study showed that rivaroxaban was noninferior to warfarin for the prevention of stroke and systemic embolism with no significant difference in clinically significant bleeding. Of interest intracranial and fatal bleeding occurred less frequently in the rivaroxaban group.
Comments:
The impressive results of the RE-LY trial using dabigatran (Pradaxa®, Boehringer Ingelheim), a competitive thrombin inhibitor in an open label study, showed that at the dose of 110 mg b.i.d. dabigatran was noninferior to warfarin for the prevention of stroke or systemic embolism with a 20% reduction in major bleeding, and at a dose of 150mg b.i.d. was superior to warfarin with no difference in major bleeding. The ROCKET-AF, a double-blind trial, showed that rivaroxaban, a Xa inhibitor was noninferior to warfarin in terms of efficacy with no difference in bleeding rates. Both dabigatran and rivaroxaban reduced the rate of intracranial bleeding. Dabigatran has been approved by the FDA for the 150mg dose and 75mg dose for patients with renal dysfunction on October 20, 2010. The dosing of dabigatran is twice a day. The administration of rivaroxaban is once a day. The characteristics of the trial design and of the population in the 2 studies were obviously different. The 2 agents will compete for the warfarin market in the coming years.
S. Lévy (No conflict of interest to declare)
Reference
This double-blind international multicenter trial randomly assigned 14,264 patients with nonvalvular AF to receive rivaroxaban (20mg daily or 15mg in patients with creatinine clearance of 30 to 49ml) or adjusted dose warfarin (target INR 2 to 3). The primary analysis was designed to determine whether rivaroxaban was noninferior in respect to the primary endpoint of stroke or systemic embolism.
The primary endpoint occurred in 188 patients of the rivaroxaban group (1.7%) and in 241 patients of the warfarin group (2.2%) p<0.001 for non-inferiority (hazard ratio for rivaroxaban 0.79;95% CI,0.66 to 0.96). Intention to treat analysis showed that the primary endpoint occurred in 269 patients of the rivaroxaban group (2.1%per year) and in 306 patients of the warfarin group (2.4% per year)
Bleeding: major and nonmajor clinically relevant bleeding occurred in 14.9% (1475 patients) of the rivaroxaban group and in 14.5% (1449 patients) of the warfarin group (P=0.44)
This study showed that rivaroxaban was noninferior to warfarin for the prevention of stroke and systemic embolism with no significant difference in clinically significant bleeding. Of interest intracranial and fatal bleeding occurred less frequently in the rivaroxaban group.
Comments:
The impressive results of the RE-LY trial using dabigatran (Pradaxa®, Boehringer Ingelheim), a competitive thrombin inhibitor in an open label study, showed that at the dose of 110 mg b.i.d. dabigatran was noninferior to warfarin for the prevention of stroke or systemic embolism with a 20% reduction in major bleeding, and at a dose of 150mg b.i.d. was superior to warfarin with no difference in major bleeding. The ROCKET-AF, a double-blind trial, showed that rivaroxaban, a Xa inhibitor was noninferior to warfarin in terms of efficacy with no difference in bleeding rates. Both dabigatran and rivaroxaban reduced the rate of intracranial bleeding. Dabigatran has been approved by the FDA for the 150mg dose and 75mg dose for patients with renal dysfunction on October 20, 2010. The dosing of dabigatran is twice a day. The administration of rivaroxaban is once a day. The characteristics of the trial design and of the population in the 2 studies were obviously different. The 2 agents will compete for the warfarin market in the coming years.
S. Lévy (No conflict of interest to declare)
Reference
- Patel et al. Rivaroxaban versus warfarin in nonvalvular atrial fib rillation. N Engl J Med 2011;365:883-91.
- Connolly S et al.. Dabigatran versus warfarin in atrial fibrillation. N Engl J Med 2009;361:1139-51.
