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

BJOG. 2017 Oct;124(11):1672-1679. doi: 10.1111/1471-0528.14358. Epub 2016 Oct 5.

Abstract

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.

Keywords: Arterial thromboembolism; drospirenone; drug safety; oral contraceptives.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Androstenes / adverse effects
  • Androstenes / therapeutic use*
  • Case-Control Studies
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Oral, Combined / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Levonorgestrel / therapeutic use*
  • Middle Aged
  • Risk Factors
  • United Kingdom / epidemiology
  • Venous Thromboembolism / chemically induced
  • Venous Thromboembolism / epidemiology*
  • Young Adult

Substances

  • Androstenes
  • Contraceptives, Oral, Combined
  • Levonorgestrel
  • drospirenone