Study Finds Apixaban Reduces Stroke Risk in Atrial Fibrillation Patients

When compared with aspirin, apixaban, a factor Xa inhibitor, was found to significantly reduce the risk of stroke or systemic embolism in patients with atrial fibrillation who are not suitable for vitamin K antagonist therapy, according to a new double-blind study. The findings from the study were reported in the New England Journal of Medicine [2011;364(9):806-817].

Previous research has found that patients with atrial fibrillation are at a higher risk of stroke, but treatment for these patients is complicated. Vitamin K antagonist therapy has been found to be more effective in preventing stroke in those with atrial fibrillation than aspirin; however, vitamin K antagonist therapy is not suitable for everyone. Apixaban is a direct inhibitor of factor Xa and may be another treatment option for these individuals.

In 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, researchers designed a double-blind study to test the efficacy and safety of apixaban in patients with atrial fibrillation who were determined unsuitable for vitamin K antagonist therapy.

During the double-blind study, 5599 patients with atrial fibrillation and an increased risk of stroke from 522 centers in 36 countries were randomized to either receive 5 mg of apixaban twice daily or 81 to 324 mg of aspirin daily. Those who were assigned to apixaban also received an aspirin placebo, while those assigned to aspirin also took an apixaban placebo. Patients had to have at least 1 of the following risk factors for stroke: prior stroke or transient ischemic attack, an age of ≥75 years, arterial hypertension (receiving treatment), diabetes mellitus (receiving treatment), heart failure (New York Heart Association class ≥2 at enrollment), a left ventricular ejection fraction of ≤35%, or documented peripheral artery disease. Patients were also required to be ≥50 years of age and have documentation of atrial fibrillation within 6 months before enrollment or be diagnosed with atrial fibrillation during a 12-lead electrocardiogram on the day of the screening.

Researchers identified the primary outcome of the trial as the occurrence of stroke or systemic embolism. Other outcomes in the AVERROES study were the occurrence of major bleeding, rates of myocardial infarction, death from vascular causes, death from any cause, and a composite of major vascular events. The study was terminated early by the Data and Safety Monitoring Board after a clear benefit of apixaban was identified. Researchers found that apixaban reduced the risk of stroke or systemic embolism by more than 50% when compared with aspirin, without significantly increasing bleeding risk.

According to the findings, there were 51 incidents of stroke or systemic embolism in the apixaban group, while there were 113 incidents among the aspirin group (hazard ratio [HR] with apixaban, 0.45; 95% confidence interval [CI], 0.32-0.62; P<.001). In addition, the rates of death were lower in the apixaban (3.5% per year) group compared with the aspirin group (4.4% per year, HR, 0.79; 95% CI, 0.62-1.02; P=.07). The risk of a first hospitalization due to cardiovascular reasons was also less with apixaban.

Researchers also noted that there were significantly fewer serious adverse events in the apixaban treatment group than the aspirin group (22% vs 27%; P<.001). When it came to major bleeding events, researchers noted 44 incidents in the apixaban group and 39 incidents in the aspirin group (HR with apixaban, 1.13; 95% CI, 0.74-1.75; P=.57). The HR for minor bleeding events in the apixaban group was 1.24 (95% CI, 1.00-1.53; P=.05). In conclusion, the authors of the study believe this latest trial shows a substantial clinical benefit to apixaban. They acknowledged, however, that terminating the study early could have been a possible limitation, but said the statistical threshold for stopping the trial was very high.