1. In patients with atrial fibrillation who were unable to receive warfarin for any reason, the use of apixaban reduced the risk of stroke and systemic embolism when compared to aspirin.
2. There were no significant differences between the groups in the risk of major bleeding.
Original Date of Publication: March 2011
Study Rundown: Atrial fibrillation is a common arrhythmia that increases the risk of stroke and other systemic emboli. Historically, patients with atrial fibrillation have been treated with warfarin, a vitamin K antagonist, to reduce their risk of such embolic events. Warfarin, however, has a narrow therapeutic range and requires regular monitoring. As many as 1 in 3 patients who have an indication for warfarin therapy refuse it, while those who do start the medication typically remain within the therapeutic range less than 60% of the time. Though aspirin has a modest effect reducing the risk of stroke in these patients, newer antithrombotic agents, like the factor Xa inhibitor apixaban, had shown promise in previous trials without requiring regular monitoring.
The Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial was conducted to explore the safety and efficacy of apixaban in these patients. In summary, this large, multicenter randomized trial demonstrated that apixaban was more effective than aspirin at preventing stroke and systemic embolism, while not increasing the risk of bleeding events. Thus, in patients with atrial fibrillation and in whom warfarin therapy is inappropriate or poorly tolerated, apixaban provides a better alternative than aspirin.
In-Depth [randomized controlled trial]: This multicenter, double-blind, randomized control trial was conducted at 522 centers in 36 countries to gauge the safety and effectiveness of apixaban as compared to aspirin in patients with atrial fibrillation. The trial enrolled 5599 patients who were older than 50 years of age, had atrial fibrillation, and for whom warfarin therapy had been discontinued or had never been initiated. Additionally, all patients had at least 1 risk factor for stroke (age >75 years, prior stroke or TIA, hypertension, diabetes mellitus, peripheral vascular disease, or congestive heart failure). Patients were excluded if they had any other indication for long-term anticoagulation, a serious prior bleeding event, or an increased risk of bleeding. Eligible patients were randomized to receive either apixaban 5 mg twice daily or 81–324 mg of aspirin daily. Of note, patients older than 80 years, had body weight <60 kg, or with renal insufficiency were eligible to receive a reduced dose of apixaban (2.5 mg twice daily). The primary outcome was the incidence of stroke or systemic embolism, while the primary safety outcome was major bleeding.
The study was stopped early, after a mean follow-up of 1.1 years, when the data and safety monitoring committee observed a larger than expected treatment benefit in the apixaban cohort. There were 51 primary outcome events observed in the apixaban group compared to 113 in the aspirin cohort (HR 0.45, 95%CI 0.32-0.62, p < 0.001). There was a non-significant trend towards lower overall mortality (HR 0.79, 95%CI 0.62-1.02, p = 0.07). There were no significant differences between the two groups in the incidence of major bleeding (HR 1.13, 95%CI 0.74-1.75, p = 0.57).
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