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.