The novel anticoagulant apixaban significantly reduced the risk of stroke or systemic embolism without increasing the risk of major bleeding or intracranial hemorrhage in atrial fibrillation patients. The results were so beneficial that the data and safety monitoring board stopped the trial early, according to a study published Feb. 10 in the New England Journal of Medicine and simultaneously presented at the American Stroke Association's International Stroke Conference in Los Angeles.

While vitamin K antagonists have been shown to prevent strokes in patients with atrial fibrillation (AF), a number of patients are unable to receive the therapy. “Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients,” the authors wrote.

To study the possible effectiveness of apixaban in AF patients at an increased risk for stroke, Stuart J. Connolly, MD, of the Population Health Research Institute, McMaster University and Hamilton Health Sciences in Hamilton, Ontario, and colleagues randomized 5,599 patients who were unsuitable to take vitamin K antagonists either a 5 mg twice daily dose of apixaban or a 81 to 324 mg per day aspirin dose, to assess whether apixaban was effective.

The mean follow-up period of the AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study was 1.1 years and the primary outcome was the occurrence of stroke of systemic embolism. Prior to enrollment, 40 percent of patients were administered a vitamin K antagonist.

The researchers reported that a total of 51 primary outcome events occurred in patients administered apixaban compared with 113 in those those who received aspirin therapy. The rates of death were reported to be 3.5 percent per year in those administered apixaban and 4.4 percent per year in those administered aspirin. Forty-four cases of major bleeding were reported in the apixaban group and 39 in the aspirin group. Additionally, the researchers reported 11 cases of intracranial bleeding with apixaban and 13 with aspirin.

Lastly, the researchers noted that the risk of first hospitalization for cardiovascular causes was lower in the apixaban group when compared with aspirin, 12.6 percent per year versus 15.9 percent per year.

Apixaban reduced the risk of stroke or systemic embolism by over 50 percent in patients who were deemed unsuitable to receive vitamin K antagonists, the authors noted.

“[I]ndirect comparisons suggest that apixaban is more effective than clopidogrel plus aspirin and at least as effective as warfarin,” the authors wrote. This hypothesis is being analyzed in the ARISTOTLE trial.

“On the basis of the results of the intention-to-treat analysis, treating 1,000 patients for one-year with apixaban rather than with aspirin would prevent 21 strokes or systemic emboli, nine deaths and 33 hospitalizations for cardiovascular causes, at the cost of two major bleeding events,” the authors noted.

Limitations of the study stemmed from the fact that the study's observation period was limited due to the trial being stopped early.

The AVERROES trial was funded by Bristol-Myers Squibb and Pfizer.