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

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 hormonal contraceptive (CHC) use, some women continue or start after a first VTE. We aimed to evaluate the VTE recurrence risk of HC use in premenopausal women. Methods Premenopausal women with a first VTE, included in the MEGA 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 (HR) with 95% confidence intervals (95%CI), adjusted for age and BMI at baseline and thromboprophylaxis use during follow-up. Results 650 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. non-use: 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 non-use. Recurrence risk for levonorgestrel-releasing intra-uterine device use was similar with non-use (HR:0.9, 95%CI:0.3-3.1). Conclusions 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 a levonorgestrel-releasing intra-uterine device as a safe alternative.