DOACs Versus VKAs in Older Adults Treated for Acute Venous Thromboembolism: Systematic Review and Meta-Analysis

BACKGROUND/OBJECTVES: Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years). METHODS: Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies. RESULTS: Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR =.56; 95% confidence interval [CI] =.38-.82). There was no statistically significant difference in the safety outcomes (RR =.77; 95% CI =.56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome. CONCLUSION: In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.