Hormonal contraception and risk of major adverse cardiovascular events: A nationwide registry study from Finland

OBJECTIVES: In this study, we assessed the association of modern systemic hormonal contraception (HC), including newly introduced estradiol-containing combined oral contraceptives, with major adverse cardiovascular events (MACE): myocardial infarction [MI] and ischemic stroke [IS], during 2018-2019. STUDY DESIGN: A prospective registry-based cohort study including all 15-49-year-old women residing in Finland in 2017, using HC. We identified women from the national prescription register and incident cases of MACE from the national patient register, yielding 584,236 women and 1167,685 person-years. We analysed cases and their 1:4 age-matched controls in a nested case-control design assessing the association between use vs. non-use of different HC and risk of MACE. Altogether 19.1% of women used combined hormonal contraceptives (CHC), 8.0% ethinylestradiol (EE) and 3.7% estradiol (E2) containing pills while 7.5% used progestin-only-pills (POP). RESULTS: We recorded altogether 334 cases of MACE (84 MI and 250 IS), with an incidence rate of 28.6/100,000 person-years (7.2/100,000 for MI and 21.4/100,000 for IS). Compared to non-use of HC, the adjusted odds ratios (95% CI) of MACE were 1.24 (0.78 - 1.96) and 1.37 (0.73- 2.57) among users of EE and E2 containing HC, and 1.04 (0.64 -1.71) among users of POP. CONCLUSION: We found no increased risk of MACE associated with use of CHCs containing either EE or E2, or with POP, compared to non-use. We speculate that the cardiovascular safety of modern use of HC is linked both to improved safety of modern contraceptives and their appropriate use. IMPLICATIONS: The present findings are reassuring concerning the cardiovascular safety of modern HC, suggesting that use of modern hormonal contraceptives, when aligned with current guidelines, does not significantly increase the risk of MACE.