Apixaban May Join Wafarin Combatting Clot For Patients With Atrial Fibrillation.

According to a post on NEJM blog and the release of the primary results of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE; ClinicalTrials.gov number, NCT00412984) indicate that Apixaban is actually superior to Wafarin.
The trial was to find if Apixaban was non inferior to Wafarin but the trail investigators found that apixaban was actually superior, reducing the risk of stroke or systemic embolism by 21% and the risk of major bleeding by 31%. In predefined hierarchical testing, apixaban, as compared with warfarin, also reduced the risk of death from any cause by 11%.

The Apixaban results follow two other, phase 3 trials that compared new anticoagulants with warfarin in patients with atrial fibrillation:
the Randomized Evaluation of Long-Term Anticoagulation Therapy trial (RE-LY, NCT00262600)(Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151[Erratum, N Engl J Med 2010;363:1877.]
Full Text | Medline ) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF, NCT00403767)- (Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891 Full Text  | Medline ). The RE-LY trial evaluated the direct thrombin inhibitor dabigatran in two different doses, 110 mg and 150 mg, both administered twice daily. ROCKET AF evaluated the direct factor Xa inhibitor rivaroxaban at a dose of 20 mg once daily.

The trials have a number of similar conclusions. Apixaban, dabigatran, and rivaroxaban, as compared with warfarin, all significantly reduce the risk of hemorrhagic stroke. In fact, in all the studies, the reductions in the primary efficacy end point — which included hemorrhagic as well as ischemic stroke — were greatly influenced by this dramatic reduction in the risk of hemorrhagic stroke. Of the three drugs, only dabigatran at a dose of 150 mg holds the distinction of also having significantly reduced the risk of ischemic stroke as compared with warfarin; nonetheless, even in this case, there was a greater influence on hemorrhagic stroke than on ischemic cerebrovascular events. Similarly, the risk of particularly serious bleeding was reduced with each of the three drugs, as compared with warfarin, and apixaban therapy also resulted in lower rates of all major bleeding. Thus, the newer anticoagulants boast favorable bleeding profiles as compared with warfarin in patients with atrial fibrillation.

NEJM

Rivaroxaban for Prevention of Stroke in Patients with Atrial Fibrillation Submitted To FDA For Approval

Johnson and Johnson Pharmaceuticals and Development LLC has filed a new drug application for  Rivaroxaban which is aiming to Prevent Stroke in Patients with Atrial Fibrillation.

RARITAN, N.J.--(BUSINESS WIRE)--Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) announced today that it has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for rivaroxaban, an investigational, oral, once-daily anticoagulant, for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF).

The submission is supported by data from the pivotal, global Phase 3 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) trial.

AF is the most common sustained cardiac rhythm disorder, affecting more than 2.3 million people in the U.S. In patients with AF, the heart’s irregular beat makes them vulnerable to the formation of blood clots in the atria, which can travel to the brain, potentially resulting in a stroke. Strokes can lead to major physical and behavioral impairments, or even death. People living with AF are at a five-fold increased risk for stroke compared with the general population, and almost one-third will suffer from a stroke in their lifetimes.

J&JPRD also announced today that it has submitted its complete response to the FDA seeking approval to use rivaroxaban for the prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing total hip or total knee replacement surgery. The submission includes specific information requested by the FDA in a complete response letter issued to J&JPRD on May 28, 2009, and is primarily supported by data from the pivotal, global Phase 3 RECORD (REgulation of Coagulation in major Orthopedic surgery reducing the Risk of DVT and PE) clinical trial program.

More information about the rivaroxaban clinical development program, and the diseases for which it is being developed, may be accessed at http://www.jnjpharmarnd.com/jnjpharmarnd/rivaroxaban.html.

About Rivaroxaban

Rivaroxaban is a novel oral anticoagulant being evaluated for the prevention and treatment of a broad range of disorders in which blood clotting plays a major role. In clinical studies, the compound has shown no requirement for routine laboratory coagulation monitoring, and limited risk for food and drug interactions. The extensive program of clinical trials evaluating this compound makes rivaroxaban the most studied oral, direct Factor Xa inhibitor in the world today. By the time of its completion, more than 65,000 patients will have participated in the rivaroxaban clinical development program. Rivaroxaban is being developed jointly by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., which is part of the Johnson & Johnson Family of Companies, and Bayer HealthCare AG.