Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women

Judith P L Verlaan; Bernadine H Stegeman; Jasmijn F Timp; Luuk J J Scheres; Linda E Flinterman; Frans M Helmerhorst; Frits R Rosendaal; Suzanne C Cannegieter; Astrid van Hylckama Vlieg

doi:10.1016/j.jtha.2024.03.014

Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women

J Thromb Haemost. 2024 Mar 28:S1538-7836(24)00172-7. doi: 10.1016/j.jtha.2024.03.014. Online ahead of print.

Authors

Judith P L Verlaan¹, Bernadine H Stegeman², Jasmijn F Timp¹, Luuk J J Scheres³, Linda E Flinterman¹, Frans M Helmerhorst¹, Frits R Rosendaal¹, Suzanne C Cannegieter⁴, Astrid van Hylckama Vlieg⁵

Affiliations

¹ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
² Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Internal Medicine, Section Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Knowledge Institute of the Dutch Association of Medical Specialists, Utrecht, The Netherlands.
³ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Internal Medicine, Section Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: a.van_hylckama_vlieg@lumc.nl.

PMID: 38554933
DOI: 10.1016/j.jtha.2024.03.014

Abstract

Background: Extensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE.

Objectives: We aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women.

Methods: Premenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010. Data on HC use were available through linkage to the Dutch Foundation for Pharmaceutical Statistics. The risk of recurrence was assessed 1) during anticoagulant therapy and 2) after cessation of anticoagulant therapy. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs adjusted for age and body mass index at baseline and thromboprophylaxis use during follow-up.

Results: Six hundred fifty women were uniquely linked and followed for a total of 3538 person-years (median, 6.1 years), during which 57 VTE recurrences occurred. Five occurred (8.8%) during anticoagulation treatment, with no clear risk difference for CHC use vs nonuse (HR, 0.8; 95% CI, 0.1-8.2). After anticoagulation cessation, CHC use was associated with a 2.4-fold higher risk of recurrence (HR, 2.4; 95% CI, 1.2-5.0) compared with nonuse. Recurrence risk for levonorgestrel-releasing intrauterine device use was similar to that for nonuse (HR, 0.9; 95% CI, 0.3-3.1).

Conclusion: CHC use after a first VTE is safe during anticoagulant use but substantially increases the risk of a recurrent VTE event in absence of anticoagulant use. This study adds to the evidence regarding the use of a levonorgestrel-releasing intrauterine device as a safe alternative.

Keywords: contraceptive; hormones; recurrence; thrombosis; women.