Risk of recurrence in women with venous thromboembolism related to estrogen‐containing contraceptives: Systematic review and meta‐analysis

BACKGROUND: The risk of recurrence after a venous thromboembolism (VTE) related to estrogen‐containing contraceptives is a key driver to guide anticoagulant treatment decisions. OBJECTIVE: To estimate the incidence rate of recurrent VTE after discontinuation of anticoagulant treatment in women with a first episode of VTE related to estrogen‐containing contraceptives. METHODS: Embase, MEDLINE, and the CENTRAL were searched from 1 January 2008 to 27 May 2021 for prospective and retrospective studies reporting on recurrence after a first VTE related to estrogen‐containing contraceptives. Risk of bias was assessed using QUIPS tool. Recurrence rates per 100 patient‐years were pooled using Knapp‐Hartung random‐effects meta‐analysis. Incidence rates were reported separately based on study follow‐up duration (≤1 year, 1–5 years, and >5 years) and for several subgroups. RESULTS: A total of 4,120 studies were identified, of which 14 were included. The pooled recurrence rate was 1.57 (95%‐CI: 1.10–2.23; I(2) = 82%) per 100 patient‐years. Recurrence rates per 100 patient‐years were 2.73 (95%‐CI: 0.00–3643; I(2) = 80%) for studies with ≤1 year follow‐up, 1.35 (95%‐CI: 0.68–2.68; I(2) = 44%) for studies with 1–5 years follow‐up, and 1.42 (95%‐CI: 0.84–2.42; I(2) = 78%) for studies with >5 years follow‐up. CONCLUSION: Among women with VTE associated with estrogen‐containing contraceptives, the risk of recurrence after stopping anticoagulation is low, which favors short‐term anticoagulation. Large prospective studies on VTE recurrence rates and risk factors after stopping short‐term anticoagulants are needed.