Apixaban Approved in Europe for stroke prevention in AF

The European Commission has approved apixaban ( Eliquis, Bristol-Myers Squibb/Pfizer Inc) for the prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation (AF) with 1 or more risk factors, the companies announced today.

Apixaban is an oral direct factor Xa inhibitor, the only oral anticoagulant to demonstrate risk reduction superior to that of warfarin in stroke and systemic embolism, as well as major bleeding and all-cause death, the companies note in their statement. This is the first regulatory approval in any market for apixaban for stroke prevention in AF; the drug is under regulatory review now in the United States by the Food and Drug Administration (FDA). It is already approved in the European Union for the prevention of venous thromboembolic events in patients undergoing elective hip or knee replacement.

"The approval of Eliquis represents an important new treatment option for health care professionals, who now have an oral anticoagulant with superior outcomes versus warfarin in the reduction of stroke, major bleeding and death in patients with nonvalvular atrial fibrillation," Lars Wallentin, director and professor of cardiology at Uppsala Clinical Research Center and University Hospital, Sweden, notes in the release.

European approval was based on results of the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) trials, including about 24,000 patients with nonvalvular AF, reported previously by Medscape Medical News. However, in the United States, the companies reported in June that the FDA had issued a complete response letter, requesting additional information on "data management and verification" in the ARISTOTLE trial, although they noted the agency hadn't requested any new studies.

Subsequently, they reported that the FDA had accepted their resubmission for apixaban in September. The FDA deemed the resubmission to be complete and assigned a new Prescription Drug User Fee Act (PDUFA) goal date of March 17, 2013.

The new approved indication is for apixaban at a dose of 5 mg twice daily in patients with nonvalvular AF patients who have 1 or more risk factors, including prior stroke or transient ischemic attack, age 75 years or older, hypertension, diabetes mellitus, or symptomatic heart failure (defined as New York Heart Association class II or higher).

The first-line use of apixaban and other new oral anticoagulants, including dabigatran ( Pradaxa, Boehringer Ingelheim) and rivaroxaban ( Xarelto, Bayer/Johnson & Johnson), is already recommended by European Society of Cardiology guidelines for the management of AF.

Although apixaban is not yet approved in the United States, the latest American Heart Association/American Stroke Association scientific advisory on new oral antithrombotic agents to prevent stroke in patients with nonvalvular AF also includes it among the agents recommended to prevent a first or recurrent stroke.