Drospirenone‐containing combined oral contraceptives and the risk of arterial thrombosis: a population‐based nested case‐control study

ObjectiveTo compare the rate of arterial thromboembolism (ATE) of drospirenone‐containing COCs to that of levonorgestrel‐containing COCs.DesignPopulation‐based cohort study.SettingUnited Kingdom's Clinical Practice Research Datalink (CPRD), which contains clinical records for >11 million patients.PopulationWomen aged 16–45 years prescribed a drospirenone‐ or levonorgestrel‐containing COC between May 2002 and June 2012.MethodsWe conducted nested case‐control analyses using risk set sampling to randomly select up to 10 controls for each ATE case, matched on age, cohort entry year, CPRD registration year, COC user type (first‐time ever, new, switcher, or prevalent users), duration of COC use, duration of progestin‐only or implantable contraceptive use, pre‐cohort entry duration of drospirenone and levonorgestrel use, and duration of follow up.Main outcome measuresWe used conditional logistic regression to estimate hazard ratios and 95% confidence intervals (CIs), adjusted for high‐dimensional propensity scores.ResultsOur cohort included 339 743 women followed over a mean 4.4 years, during which 228 ATE cases occurred: 37 myocardial infarctions, 170 strokes, and 21 other ATEs; overall rate: 1.5 events per 10 000 person‐years (PYs). After adjusting for potential confounders, the hazard ratio for ATE with current use of drospirenone‐containing COCs versus current use of levonorgestrel‐containing COCs was 0.89 (95% CI 0.35, 2.28), corresponding to a rate difference of −0.16 events per 10 000 PYs.ConclusionsThe overall rate of ATE in this population is low regardless of which COC was taken. We found little evidence of a difference in the rate of ATE with drospirenone‐ versus levonorgestrel‐containing COCs.Tweetable abstractLittle evidence was found of a greater incidence of arterial thrombosis with drospirenone versus levonorgestrel contraceptives.