Because of the high recurrence risk, guidelines recommend indefinite anticoagulation in women with a first unprovoked proximal deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). The optimal duration of anticoagulation in women who had venous thromboembolism (VTE) while using estrogens is unknown. We therefore compared the risk of recurrent VTE between women who used estrogens at the time of first VTE and women who did not.
This analysis was performed within the frame of the Austrian Study on Recurrent Venous Thromboembolism (AUREC), an on-going prospective observational study. Patients with a first objectively confirmed DVT of the leg and/or PE who had received anticoagulants for 3 to 18 months were included. Exclusion criteria were: age < 18 years; VTE associated with surgery, trauma, cancer or pregnancy; long-term anticoagulation; natural inhibitor deficiency; lupus anticoagulant; homozygosity or double heterozygosity for factor V Leiden and/or the prothrombin mutation. Women were advised to refrain from further estrogen use and were excluded in case of non-adherence. The study end point was recurrent symptomatic DVT and/or PE verified by imaging. The local ethics committee approved the study and all patients gave written informed consent.
We followed 630 women (mean age 46 +/- 17 years) who had been treated with oral anticoagulants for 7 (+/- 3) months for an average of 69 (+/- 52) months. Recurrent VTE was recorded in 71 patients (11%). Recurrent VTE occurred in 22 (7%) of 333 estrogen users and in 49 (17%) of 297 non-users. After 1, 2 and 5 years, the cumulative probability of recurrence was 1% (95% CI 0-2), 1% (95% CI 0-2) and 6% (95% CI 3-9) among estrogen users and 5% (95% CI 2-7), 9% (95% CI 6-13) and 17% (95% CI 12-22) among non-users, respectively (p < 0.001, Figure). Compared to non-users, estrogen users had a relative risk (RR) of recurrent VTE of 0.4 (95% CI 0.2-0.8) after adjustment for age, site of first VTE and factor V Leiden carrier status. Compared to non-users in the respective age groups, the RR of recurrent VTE was 0.4 (95% CI 0.2-0.8) among estrogen containing contraceptive users and was 0.7 (95% CI 0.3-1.5) among women using estrogen containing hormone replacement therapy.
Women who had their first VTE while using estrogens have a low risk of recurrent VTE. The recurrence risk is particularly low in estrogen containing contraceptive users. We therefore propose that these women should receive anticoagulant therapy for no longer than 3 months.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.
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