AVERROES: Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Strokes
Background
Patients with atrial fibrillation have an increased risk of stroke. Vitamin K antagonists (VKA), such as warfarin, are effective for reducing stroke but are associated with an increased risk of hemorrhage. In addition, the management of VKA therapy is complex, requiring frequent monitoring due to genetic variability and multiple drug and diet interactions. Many patients with atrial fibrillation cannot be maintained effectively on a VKA, others have had complications and some patients refuse to take it. For patients who are unsuitable for VKA therapy, the only alternative treatment is aspirin, which is only modestly effective. Apixaban is an investigational oral anticoagulant that selectively inhibits factor Xa. Studies in venous thromboembolism prophylaxis have demonstrated that apixaban is effective and that it has a favourable risk benefit ratio compared with low-molecular-weight heparin.
Purpose
The purpose of AVERROES was to evaluate apixaban for the prevention of stroke or systemic embolism in patients with atrial fibrillation at risk for stroke who are unsuitable for therapy with a VKA. Apixaban was compared to standard therapy for these patients, which is aspirin.
Methods
AVERROES was a double-blind, randomized, active controlled evaluated of apixaban compared to aspirin. Patients with documented atrial fibrillation and at least one risk factor for stroke who are also unsuitable for therapy with a VKA were randomized 1:1 to receive either apixaban 5 mg bid (2.5 mg bid in selected patients) or aspirin (81-324 mg per day). The study was performed in 520 sites worldwide and enrollment of 5,600 patients was completed in December 2009. The Data Monitoring Committee (DMC) performed its first formal interim analysis of efficacy when 50% of expected primary outcome events had occurred and again reviewed efficacy three months later, on May 28, 2010, according to the DMC charter. Based on overwhelming evidence of efficacy against stroke or systemic embolism, together with an excellent safety profile, they recommended termination of the study so that all patients could receive open-label apixaban. This recommendation was accepted by the Steering Committee and the study sponsors.
Results
Preliminary results are briefly described.
Treatment groups were well balanced for all baseline factors. The mean age was 70 years. The mean CHADS2 score was 2.0. 75% of patients were receiving aspirin at the time of study enrollment and 15% were receiving an oral anticoagulant. 40% had previously been exposed to a Vitamin K antagonist. The annual rate of stroke or systemic embolism (the primary outcome) was 4.0% per year on aspirin and 1.7% per year on apixaban (Hazard Ratio 0.43, 95% CI, 0.30-0.62, p=0.000004). The rate of major hemorrhage was 1.2% per year on aspirin and 1.5% per year on apixaban (Hazard Ratio 1.26, 95% CI, 0.79-2.00, p=0.33). The rate of hemorrhagic stroke was 0.2% per year in both treatment groups (Hazard Ratio 1.15, 95% CI, 0.42-3.17, p=0.79). There was no evidence of hepatic toxicity or other major adverse events.
Conclusions
In patients with atrial fibrillation at risk for stroke and unsuitable for therapy with a VKA, apixaban reduces the risk of stroke or systemic embolism by 57% with no significant increased risk in major hemorrhage. Apixaban offers an important advantage over aspirin for prevention of stroke in these patients.
http://www.escardio.org/congresses/esc- ... RROES.aspx
ESC Congress 2010: AVERROES Study
Модератор: Pyankov Vasily
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Pyankov Vasily
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