The Effectiveness and Safety of Extended Anticoagulant Treatment in Patients with Venous Thromboembolism

Background: Current guidelines for the secondary prevention of venous thromboembolism (VTE) recommend oral anticoagulation for at least 90 days. Extending therapy has been shown to decrease the risk of VTE recurrence but comes with the increased risk of bleeding. Currently, little data are available on the optimal duration of therapy and the benefit-to-risk profile of extended anticoagulation in patients with VTE.

Objectives: To evaluate the effectiveness and safety of extending anticoagulant therapy in patients with VTE.

Methods: Using administrative claims data from US Medicare and two commercial health insurance databases (January 2010 — March 2021), we conducted a cohort study of patients who were hospitalized for VTE and initiated an oral anticoagulant (apixaban, dabigatran, edoxaban, rivaroxaban or warfarin) within 30 days of VTE discharge. Patients were required to have at least 365 days of health plan enrollment prior to VTE with no exposure to any oral anticoagulant during that period. We further required study patients to complete at least (1) 90, (2) 180, (3) 270, or (4) 360 days of continuous anticoagulation. Among patients who completed the specified initial treatment, we compared those who continued anticoagulation further with patients who discontinued treatment. Primary outcomes included VTE recurrence and hospitalization with major bleeding. Propensity score matching weights were used to adjust for confounding. Follow-up began the day after completion of initial treatment, and patients were censored on change of therapy in the primary analysis. A weighted Cox model was used to estimate adjusted hazard ratios (HRs) and 95% robust confidence intervals (CIs).

Results: We identified 90,921 eligible patients who completed 90 days; 52,892 who completed 180 days; 26,428 who completed 270 days; and 8,363 who completed 360 days of anticoagulation. Patients who completed at least 90 days were, on average, 70 years old with 57% female. Anticoagulant continuation was associated with a lower risk of recurrent VTE relative to discontinuation, with HRs ranging from 0.30 (95% CI 0.25-0.35) for therapy beyond 90 days to 0.15 (95% CI 0.08-0.26) for therapy beyond 360 days. There were no major differences in the risk of bleeding for continuation versus discontinuation with HRs from 1.16 (95% CI 0.99-1.37) for therapy beyond 90 days to 0.91 (95% CI 0.52-1.61) for therapy beyond 360 days. Findings were similar across subgroup and sensitivity analyses, including an intention-to-treat approach.

Conclusions: In this analysis of patients with VTE, extended anticoagulant treatment was associated with a lower risk of recurrent VTE and no major increase in risk of bleeding, as compared to stopping therapy.