Contemporary Meta-Analysis of Extended Direct-Acting Oral Anticoagulant Thromboprophylaxis to Prevent Venous Thromboembolism

Background: Medically ill patients remain at risk of venous thromboembolism for up to 6 weeks after hospital discharge due to factors such as immobilization and inflammation. Methods: We conducted a meta-analysis and systematic review of Phase III randomized controlled trials comparing extended use of direct oral anticoagulation (DOAC) post discharge for venous thromboembolism prophylaxis with placebo. Results: The primary efficacy outcome (composite of venous thromboembolism and mortality) occurred in 373/13,099 patients in the DOAC group (2.9%) and 477/13,309 patients in the placebo group (3.6%), with an odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.69-0.91). The secondary efficacy outcome (nonfatal symptomatic venous thromboembolism) occurred in 75/15,573 patients in the DOAC group (0.48%) and 120/15,599 in the placebo group (0.77%) with an OR of 0.62 (95% CI, 0.47-0.83). The primary safety outcome (major bleeding) occurred in 90/15,474 patients in the DOAC group (0.58%) and in 47/15,418 patients in the placebo group (0.3%) with an OR of 1.92 (95% CI, 1.35-2.73). The secondary safety (clinically relevant nonmajor bleeding) outcome occurred in 333/15,474 patients in the DOAC group (2.2%) and 191/15,418 patients in the placebo group (1.2%) with an OR of 1.75 (95% CI, 1.46-2.1). The extended use of venous thromboembolism prophylaxis post discharge results in decreased venous thromboembolism events but increased bleeding risk. Our cost-effective analysis of extended DOAC use vs placebo showed superiority of the DOAC group. Conclusion: In conclusion, given the mortality benefit and cost benefit, extended thromboprophylaxis is a beneficial strategy to efficiently reduce the risk of venous thromboembolism.