• Arrhythmias
• Cerebrovascular Disease
• Cardiology Clinical Trials

The oral direct factor Xa inhibitor apixaban was superior to aspirin (ASA) therapy for the reduction of stroke or systemic embolism risk in patients with atrial fibrillation (AF) who were unsuitable for vitamin K antagonist (VKA) therapy. The phase III Apixaban versus Acetylsalicylic Acid to Prevent Strokes (AVERROES; NCT00496769) trial was terminated early at the suggestion of the Data Monitoring Committee due to clear evidence of efficacy at the predefined interim analysis in May 2010. Stuart Connolly, MD, Population Health Research Institute, Hamilton, Ontario, Canada, discussed results from the preliminary analysis of AVERROES and the clinical implications of this study.

AF presents a high risk of stroke, which can be offset by the use of VKA therapy. However, this regimen is unsuitable for many patients because of increased bleeding risk, compliance issues, and difficulties that are related to anticoagulation monitoring or control. Therefore, a safe, easy-to-use alternative to VKA therapy is warranted. Apixaban offers a possible antithrombotic solution to those who are unable to take VKA, with the added advantages of a 12-hour half-life, multiple excretion pathways (25% renal), and no routine coagulation monitoring requirements.

AVERROES was a double-blind, randomized, multicenter, international, trial that included 5600 patients with AF and at least one risk factor for stroke who were unsuitable candidates for VKA therapy. Patients were randomized to receive either apixaban (5 mg twice daily or 2.5 mg twice daily in selected patients; n=2809) or ASA (81–324 mg daily, with 91% receiving ≤162 mg daily; n=2791). The patients were well matched at baseline. The mean patient age was 70 years, and median follow-up was 1 year. The primary endpoint was the composite of stroke or systemic embolic event (SEE), and the primary safety endpoint was major hemorrhage. Secondary endpoints included a composite of stroke, SEE, myocardial infarction or vascular death, and total death.

Preliminary data revealed that the incidence of stroke or SEE was significantly lower in the apixaban group compared with the ASA group (RR, 0.46; 95% CI, 0.33 to 0.64; p<0.001). Apixaban reduced the incidence of stroke by >50% compared with ASA (1.5% for the apixaban group vs 3.3% for ASA; p<0.001), without a significant increase in major bleeding. The rate of major bleeding was similar between the two groups (hemorrhagic stroke was 0.2% for both groups). The composite secondary outcome and rate of total death also favored apixaban over ASA therapy.

Apixaban appeared to be safe and well tolerated compared with ASA, without evidence of liver toxicity. The reductions in stroke and SEE risk occurred without a significant increase in bleeding. Dr. Connolly concluded that for every 1000 patients who were treated with apixaban rather than ASA for 1 year, 18 strokes, 10 deaths, and 31 cardiovascular hospitalizations would be prevented at the cost of 2 major bleeds. These findings demonstrate that apixaban is appropriate for stroke prevention in AF patients who are unsuitable candidates for VKA therapy.

• © 2010 MD Conference Express