Original research article Risk factors for recurrence of venous thromboembolism associated with the use of oral contraceptives ☆,☆☆ Hélène Vaillant-Roussel a, ⁎ , Lemlih Ouchchane b , Claire Dauphin c , Pierre Philippe d , Marc Ruivard d a Department of Family Medicine, Faculté de Médecine, Université de Clermont-Ferrand 1 63000 Clermont-Ferrand, France b Department of Biostatistics Medicine, Faculté de Médecine, Université de Clermont-Ferrand 1 63000 Clermont-Ferrand, France c Department of Cardiology, Centre Hospitalier Universitaire 63000 Clermont-Ferrand, France d Department of Internal Medicine, Centre Hospitalier Universitaire 63000 Clermont-Ferrand, France Received 16 March 2011; revised 19 June 2011; accepted 22 June 2011 Abstract Background: Combined oral contraceptives (COC) increase the risk of venous thromboembolism (VTE), but the risk of recurrent VTE is not precisely determined. In this retrospective cohort study, we sought the risk factors for recurrence after a first VTE that occurred in women taking COC. Study Design: Time-to-event analysis was done with Kaplan–Meier estimates. In total, 172 patients were included (43% with pulmonary embolism): 82% had no other clinical risk factor for VTE. Results: Among the 160 patients who stopped anticoagulation, the cumulative incidence of recurrent VTE was 5.1% after 1 year and 14.2% after 5 years. Significant factors associated with recurrence were renewed use of COC [hazard ratio (HR)=8.2 (2.1–32.2)], antiphospholipid syndrome [HR=4.1 (1.3–12.5)] and protein C deficiency or factor II G20210A [HR=2.7 (1.1–7)]. Pure-progestin contraception [HR=1.3 (0.5–3.0)] or factor V Leiden [HR=1.3 (0.5-3.4)] did not increase recurrence. Postsurgical VTE had a lower risk of recurrence [HR=0.1 (0.0–0.9)]. Conclusion: Further studies are warranted to determine whether testing for antiphospholipid syndrome, protein C deficiency or the factor II G20210A could modify the duration of anticoagulation. This study confirms the safety of pure-progestin contraception. © 2011 Elsevier Inc. All rights reserved. Keywords: Venous thromboembolism; Combined oral contraceptives; Recurrence 1. Introduction In women who use combined oral contraceptives (COC), i.e., an oral contraceptive that contains progestin and estrogen, the risk of venous thromboembolism [VTE; deep venous thrombosis (DVT) and/or pulmonary embo- lism (PE)] is increased by 3 to 6 times compared with nonusers [1]. The incidence of VTE during the use of COC is approximately 30–40 per 100,000 user-years [1]. In young women of reproductive age, approximately one half of cases of VTE occur during COC use [2,3]. The risk is increased with an increased dose of estrogen, with a risk ratio of 1.6 between 30 mcg and 50 mcg of ethinylestra- diol [4]. Several prospective studies including large cohorts [5,6] show that use of third-generation COC does not increase VTE risk when compared with second-generation COC. In contrast, other epidemiological and prospective studies including meta-analyses have shown an increased VTE risk following use of third-generation COC compared with second-generation COC (risk ratios varying from 1.3 to 1.7) [7–10]. A recent large cohort study confirmed these results and showed clearly that use of progestin-only pills does not carry an increased risk of VTE when compared with no use of OCs [11]. Contraception 84 (2011) e23 – e30 ☆ This work was supported by public funds (Centre Hospitalier de Clermont-Ferrand, Faculté de Médecine, Université de Clermont-Ferrand 1). ☆☆ Conflict-of-interest disclosure: The authors declare no competing financial interests. ⁎ Corresponding author. Department of Family Medicine, CHU Clermont-Ferrand, 63000 Clermont-Ferrand Cedex, France. Tel.: +334 73 750 085. E-mail address: vaillanthelene@yahoo.fr (H. Vaillant-Roussel). 0010-7824/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2011.06.008