Apixaban Approved in Canada for Stroke Prevention in AF

Susan Jeffrey


December 06, 2012

Health Canada has approved apixaban (Eliquis, Bristol-Myers Squibb/Pfizer Inc) for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (AF), 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 second regulatory approval for apixaban for stroke prevention in AF after approval in the European Union last month; 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 and in Canada for the prevention of venous thromboembolic events in patients undergoing elective hip or knee replacement.

"AF places people at an increased risk of stroke. Yet despite available treatment options, many patients remain inadequately managed or untreated," said Paul Dorian, MD, department division director, Cardiology, University of Toronto, and staff cardiac electrophysiologist, St. Michael's Hospital, Ontario, Canada, in the company statement. "New oral anticoagulants (NOACs) are now the first recommended options for most patients for stroke prevention in Canada, and by making new therapies like Eliquis available, the goal is to reduce the burden of this disease."

Like European approval, approval of apixaban in Canada 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. FDA deemed the resubmission to be complete and assigned a new Prescription Drug User Fee Act (PDUFA) goal date of March 17, 2013.

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. As a class, new oral anticoagulants are also recommended by Canadian Cardiovascular Society clinical practice guidelines as preferable to warfarin.

Despite its not yet being 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 apixaban among the agents recommended to prevent a first or recurrent stroke.