Risk of recurrence in patients with provoked venous thromboembolism: a prospective cohort study

Abstract

Venous thromboembolism (VTE) provoked by transient risk factors is generally considered low risk, supporting short-term anticoagulation. However, this paradigm is based on heterogeneous definitions of provoking factors. In a prospective cohort study, we evaluated recurrence risk using the International Society on Thrombosis and Haemostasis (ISTH) classification of major and minor transient risk factors. Patients with symptomatic deep vein thrombosis and/or pulmonary embolism who completed ≥3 months of anticoagulation were followed after treatment discontinuation. Patients with cancer, major thrombophilia, pregnancy-associated VTE, or indication for extended anticoagulation were excluded. The primary outcome was symptomatic recurrent VTE. Cumulative incidence was estimated by Kaplan-Meier analysis. The study was terminated early due to unexpectedly high recurrence risk among patients with major provoking factors. Between 2019 and 2025, 242 patients were followed for a median of 23.9 months; 72 had major and 170 minor transient risk factors. Recurrent VTE occurred in 13 patients with major and 7 with minor risk factors. At 24 months, recurrence risk was 9.5% (95% CI, 6.0-14.0) overall, 19.7% (11.0-30.2) after major, and 5.0% (2.2-9.5) after minor risk factors. No recurrence occurred in 81 women with hormone-associated VTE; after their exclusion, the recurrence risk among patients with other minor risk factors increased to 9.1% (95% CI 4.0-17.0). Recurrence after provoked VTE is not uniformly low and varies substantially by the type of transient risk factor. These findings challenge current treatment paradigms and support individualized decisions regarding anticoagulation duration.