Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.

BACKGROUND: The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial. OBJECTIVES: To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs. SEARCH STRATEGY: We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index. SELECTION CRITERIA: Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French. DATA COLLECTION AND ANALYSIS: We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding. MAIN RESULTS: Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57. AUTHOR'S CONCLUSIONS: As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk. TWEETABLE ABSTRACT: Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel).

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

OBJECTIVE: To compare the rate of arterial thromboembolism (ATE) of drospirenone-containing COCs to that of levonorgestrel-containing COCs. DESIGN: Population-based cohort study. SETTING: United Kingdom's Clinical Practice Research Datalink (CPRD), which contains clinical records for >11 million patients. POPULATION: Women aged 16-45 years prescribed a drospirenone- or levonorgestrel-containing COC between May 2002 and June 2012. METHODS: We 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 MEASURES: We used conditional logistic regression to estimate hazard ratios and 95% confidence intervals (CIs), adjusted for high-dimensional propensity scores. RESULTS: Our 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. CONCLUSIONS: The 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 ABSTRACT: Little evidence was found of a greater incidence of arterial thrombosis with drospirenone versus levonorgestrel contraceptives.