Meta-Analysis of Direct-Acting Oral Anticoagulants Compared With Warfarin in Patients >75 Years of Age.

Older patients with atrial fibrillation (AF) are at higher risk of thromboembolic events and oral anticoagulant (OAC)-related bleeding complications. This meta-analysis evaluates the efficacy and safety of direct-acting OACs (DOACs) compared with warfarin in older patients with nonvalvular AF. PubMed, Embase, and Cochrane Central databases were searched for randomized controlled trials assessing the efficacy and safety of DOACs compared with warfarin in AF patients who were >75 years old. Treatment effects and relevant standard errors were calculated from the available data. These values were imputed in software R to perform meta-analysis through generic inverse variance method. Additionally, we performed a network meta-analysis to compare the relative efficacy and safety of each OAC. Five substudies of randomized controlled trials, comprising 28,135 older participants, were included in the analysis. DOACs as a group were found to have superior efficacy compared with warfarin in reducing stroke or systemic embolization (hazard ratio 0.76, 95% confidence intervals 0.67 to 0.86, p <0.01). The rate of major bleeding was similar, but intracranial hemorrhage was significantly lower in patients randomized to a DOAC (hazard ratio 0.48, 95% confidence intervals 0.34 to 0.67, p <0.01). Apixaban was the only DOAC that significantly reduced all 3 outcomes of systemic embolization, major bleeding, and intracranial hemorrhage compared with warfarin (by 29%, 36%, and 66%, respectively). In conclusion, DOACs were found to be safer and more effective than warfarin for the treatment of nonvalvular AF in older patients. Apixaban appears to provide the best combination of efficacy and safety in this population.