Benefits from full apixaban dose outweigh bleeding risk in some with AF

By David Douglas

NEW YORK (Reuters Health) - Many patients with atrial fibrillation (AF) at risk for stroke could benefit from the full apixaban dose (5.0 mg twice daily) despite being at increased risk of bleeding, according to a secondary analysis of a large clinical trial.

As Dr. John H. Alexander explained in an email to Reuters Health, "There is concern that physicians are using the lower dose (2.5 mg) of apixaban in patients with advanced age, low body weight, or renal insufficiency because of concerns about bleeding."

"Our analysis," he added, "confirms the safety of apixaban 5 mg in patients even with (these) extremes." The 2.5 mg dose "should only be used in patients with two or three of these characteristics."

Dr. Alexander of Duke Clinical Research Institute in Durham, North Carolina, and colleagues examined data on more than 17,000 AF patients involved in the ARISTOTLE study of warfarin versus apixaban (Eliquis).

Their study, online July 22 in JAMA Cardiology, was supported by Bristol-Myers Squibb and Pfizer, which also funded the ARISTOTLE trial. Dr. Alexander and co-authors reported relationships with these and other pharmaceutical companies.

Patients randomized to apixaban with no or just one dose reduction criterion received 5.0 mg twice daily. Patients with at least two of the "ABC" dose-reduction criteria - age of at least 80 years, body weight of 60 kg or less, and creatinine level 1.5 mg/dL or higher - received apixaban 2.5 mg twice daily.

Compared with apixaban patients with no dose reduction criteria, those with one had significantly higher rates of stroke or systemic embolism (hazard ratio, 1.47) and major bleeding (HR, 1.89).

However, the bleeding risk was significantly lower with 5 mg twice daily apixaban than with warfarin for patients with one (HR, 0.68) or no dose-reduction criterion (HR, 0.72). "Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance," the researchers note.

"The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion," they conclude.

Dr. Jeffrey I. Weitz, co-author of an accompanying editorial, told Reuters Health by email, "There is systemic underdosing of apixaban in the community. The results of this analysis highlight the need for using full dose apixaban (5 mg twice daily) in most patients."

"Only those with at least 2 of the 3 ABC dose reduction criteria . . . should have their dose of apixaban reduced to 2.5 mg twice daily," agreed Dr. Weitz of Hamilton General Hospital, Ontario, Canada.

SOURCE: http://bit.ly/2aEIvQg and http://bit.ly/2avDieD

JAMA Cardiol 2016.

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