Apixaban for Stroke Prevention in Atrial Fibrillation: Why are Event Rates Higher in Clinical Practice than in Randomized Trials?—A Systematic Review
Tim A.C. de Vries, Jack Hirsh, Ke Xu, Imaad U. Mallick, Vinai Bhagirath, John W. Eikelboom, Jeffrey S. Ginsberg, Paul Krüger, Noel Chan
Abstract
BACKGROUND: Recent reports suggest an important contribution from frequent off-label use of apixaban 2.5 mg twice daily to the higher rates of thromboembolic events observed in observational studies (OSs) relative to in randomized controlled trials (RCTs), and consequently, advocate against such use in all patients. OBJECTIVES: To examine factors contributing to the higher thromboembolic event rates, we estimated the prevalence of off-label use in contemporary practice, and compared patient characteristics and rates of stroke/systemic embolism, major bleeding, and mortality by apixaban dose and by study design in a systematic review and meta-analysis. RESULTS AND DISCUSSION: -VASc scores (mean 3.6 vs. 2.9) versus those in RCTs. We observed a consistent pattern of higher rates of thromboembolic events, bleeding, and mortality in patients treated with 2.5 versus 5 mg twice daily apixaban in both OSs and RCTs. CONCLUSION: The higher risk profiles of patients in OSs versus RCTs, and higher rates of both bleeding and mortality not attributable to thromboembolism in patients treated with apixaban 2.5 versus 5 mg twice daily suggest that differences in patient characteristics are additional important contributors to the higher than expected thromboembolic event rates in clinical practice.