Continued versus discontinued oral anticoagulant treatment for unprovoked venous thromboembolism: target trial emulation

Abstract Objective To compare the effect on health outcomes of continuing or discontinuing oral anticoagulants (OACs) among patients with unprovoked venous thromboembolism (VTE) after initial treatment for at least 90 days. Design Target trial emulation. Setting Optum Clinformatics Data Mart (Optum CDM) from 1 January 2009 to 28 Februray 2025, and Medicare fee-for-service claims from 1 January 2009 to 31 December 2022, United States. Participants Adults with VTE aged ≥18 years (Optum CDM) or ≥65 years (Medicare) initiating OACs (warfarin or direct OACs) within 30 days after a first hospital admission with VTE without reversible provoking factors and who continued treatment for ≥90 days. Propensity score one-to-one matching was performed between patients who continued and those who discontinued treatment (ie, absence of a refilled prescription within 30 days). Main outcome measures The primary outcomes were hospital admission for recurrent VTE (effectiveness) and major bleeding (safety). Secondary outcomes were net clinical benefit (a composite of recurrent VTE and bleeding) and mortality. Cox proportional hazards models estimated hazard ratios and generalized linear models estimated rate differences per 1000 person years. Analyses were stratified by length of initial OAC treatment (90-179, 180-359, 360-719, 720-1079, or ≥1080 days). Results The study cohort included 30 554 propensity score matched pairs who had continued or discontinued an OAC (mean age 73.9 years, 57.0% women). After initial anticoagulation of ≥90 days, compared with those who discontinued treatment, those who continued treatment had markedly lower rates of recurrent VTE (adjusted hazard ratio 0.19, 95% confidence interval (CI) 0.13 to 0.29; adjusted rate difference per 1000 person years −25.50, 95% CI −39.38 to −11.63), higher rates of major bleeding (1.75, 1.52 to 2.02; 4.78, 1.95 to 7.61), lower mortality rates (0.74, 0.69 to 0.79; −14.31, −22.02 to −6.59), and greater net clinical benefit (0.39, 0.36 to 0.42; −21.01, −32.31 to −9.71). The greater net clinical benefit was consistent across OAC types and length of initial OAC treatment. Conclusion Based on two US nationally representative routine care databases, continuing versus discontinuing OAC after initial anticoagulation of ≥90 days was associated with lower risk of recurrent VTE, higher risk of major bleeding, and a net clinical benefit. This observation persisted among those using OACs for at least three years after VTE.