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

ELIQUIS® (apixaban), Multiple Data Presentations By Bristol-Myers Squibb and Pfizer.

Bristol-Myers Squibb And Pfizer Announce Data Presentations For Apixaban At European Society of Cardiology Congress 2011

New Data Presentations from Largest Phase 3 Clinical Trial Program for Stroke Prevention in Atrial Fibrillation

Multiple data presentations for ELIQUIS® (apixaban), an oral direct Factor Xa inhibitor being developed by Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE), will be given at the European Society of Cardiology Congress, August 27-31, 2011, in Paris, France.

Globally-conducted registrational studies evaluating ELIQUIS for the prevention of stroke in patients with atrial fibrillation will be presented during the congress. Of note is the first presentation of the comprehensive analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) during the Hot Line session on Sunday, August 28th.

Presentations on ELIQUIS at the Congress include:

About Atrial Fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia. It is estimated that more than 5 million Americans and 6 million individuals in the European Union have AF. The lifetime risk of atrial fibrillation is estimated to be approximately one in four for individuals 40 years of age or older. The underlying threat of atrial fibrillation is the increased risk of stroke, which is five times higher in people with atrial fibrillation than those without atrial fibrillation. In fact, 15 percent of all strokes in the U.S. are attributable to atrial fibrillation.

About ARISTOTLE and AVERROES

The ELIQUIS stroke prevention in atrial fibrillation clinical trial program was designed to comprehensively evaluate ELIQUIS in approximately 24,000 patients with atrial fibrillation requiring stroke prevention, including patients who are expected or demonstrated to be unsuitable for vitamin K antagonist therapy.

ARISTOTLE, a double-blind, multicenter, head-to-head Phase 3 trial, randomized more than 18,000 patients with atrial fibrillation from over 1,000 centers in about 40 countries. Patients were randomized to receive either ELIQUIS 5 mg twice daily (2.5 mg twice daily in selected patients) or dose-adjusted warfarin (titrated to a target INR range of 2.0 to 3.0). The key study outcomes were prespecified in a hierarchical manner that sequentially tested ELIQUIS versus warfarin for noninferiority on the composite endpoint of stroke or systemic embolism; superiority on the composite endpoint of stroke or systemic embolism; superiority on major bleeding; and superiority on all-cause death.

The AVERROES study evaluated ELIQUIS compared to aspirin in 5,599 patients with atrial fibrillation at risk for stroke who were demonstrated or expected to be unsuitable for vitamin K antagonist therapy.

About ELIQUIS

ELIQUIS is the approved trade name for apixaban in Europe and the proposed trade name in the United States. ELIQUIS is not approved in any country for the prevention of stroke in patients with atrial fibrillation. Bristol-Myers Squibb and Pfizer recently announced the first regulatory approval for ELIQUIS in the 27 countries of the European Union (EU) for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. Apixaban is not currently approved in the United States.

ELIQUIS is being investigated within the EXPANSE Clinical Trials Program, which is projected to include nearly 60,000 patients worldwide across multiple indications and patient populations and includes a total of nine completed or ongoing, randomized, double-blind Phase 3 trials, including ARISTOTLE and AVERROES.

In addition to stroke prevention in patients with atrial fibrillation and the prevention of VTE in patients who have undergone total hip or total knee replacement surgery, ELIQUIS is being investigated in Phase 3 trials for the treatment of VTE and the prevention of VTE in hospitalized acutely ill medical patients.

About the Bristol-Myers Squibb/Pfizer Collaboration

In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize ELIQUIS, an investigational oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb’s long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field.

Via Pfiser