Extended DOAC therapy in patients with VTE and potential risk of recurrence: A systematic review and meta-analysis

Background Guidelines recommend at least 3 months of anticoagulation for venous thromboembolism (VTE). Evidence supporting indefinite anticoagulation exists in certain conditions; however, for many patients, uncertainty regarding when to discontinue anticoagulation persists. Objective We aimed to investigate the efficacy and safety of extended direct oral anticoagulants (DOAC) therapy in patients with VTE and clinical uncertainty regarding extended anticoagulation. Methods We searched EMBASE, MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases for randomized control trials examining extended anticoagulation with DOACs as compared to non-extended therapy for the treatment of VTE. Results Of 560 citations identified by the search, three studies were eligible. Extended anticoagulation reduced VTE recurrence (relative risk [RR] 0.18, 95% confidence interval [CI] 0.12 to 0.25), and mortality (RR 0.39, 95% CI 0.19 to 0.80) with a low total number of deaths in the DOAC group (n = 12) versus placebo (n = 18). Extended anticoagulation increased clinically relevant non-major bleedings (RR 2.51, 95% CI 1.37 to 4.59). There was no difference in rates of major bleeding (RR 1.87, 95% CI 0.19 to 17.85); however, there was a low number of major bleeding events in both DOAC (n = 9) and placebo groups (n = 4). The results were mostly driven by one study (AMPLIFY-EXT), with significant heterogeneity between studies noticed when assessing bleeding outcomes. Conclusion Extended DOAC therapy for 1 year in patients with clinical uncertainty for ongoing anticoagulation can reduce VTE recurrence and mortality; however, it could increase clinically relevant non-major bleeding events.