Venous thromboembolism in users of hormonal contraception and non-steroidal anti-inflammatory drugs: a nationwide cohort study

Abstract Objective To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism. Design: Nationwide cohort study. Setting: Denmark through national registries. Participants: All 15-49-year-old women living in Denmark between the years 1996-2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment. Main outcome measure: A first-time discharge diagnosis of lower-limb deep venous thrombosis or pulmonary embolism. Results Among 2.0 million women followed for 21.0 million person-years, 8710 venous thromboembolic events occurred. Compared to non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 8.1 (95% confidence interval (CI) 6.9 to 9.6) in women not using hormonal contraception, 12.1 (10.6 to 13.9) in women using high-risk hormonal contraception, 8.7 (6.5 to 11.6) in users of medium-risk hormonal contraception, and 5.1 (2.9 to 9.1) with low/no-risk hormonal contraception. Compared to non-use of NSAIDs, the number of extra venous thromboembolic events per 100,000 one-week NSAID treatments was 4 in women not using hormonal contraception, 18 in women using high-risk hormonal contraception, 9 in users of medium-risk hormonal contraception, and 2 in women using low/no-risk hormonal contraception. Conclusions NSAID use was positively associated with the development of venous thromboembolism. The association was stronger in women concomitantly using high-risk hormonal contraceptives and weaker in women using low/no-risk hormonal contraception. Women requiring both hormonal contraception and regular use of NSAIDs should be advised accordingly.