Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study

Your recent article on drospirenone and venous thromboembolism (VTE) highlighted vast differences between drospirenone and second-generation oral contraceptives (OC) users for smoking [26.28 % versus 18.48%] and obesity [13.41% versus 26.44%] [1]. These differences were not observed in the European Active Surveillance Study which interviewed patients at baseline [2], or the INGENIX study [3], which sampled 10% of patients to assess for these covariates. Do you think this reflects differences in prescribing practices between Israel and either Germany or the United States? Might these differences suggest the presence of other potential unmeasured confounders?

The selective prescribing of drospirenone in patients with polycystic ovary syndrome (PCOS), discussed at the December 8th FDA advisory committee meeting, raised concern for confounding by indication. We recently acquired an OC cohort in IMS data to evaluate gall bladder disease with use of drospirenone [4]. In further evaluation, we found that 6.05% of women taking drospirenone/ethinyl-estradiol 0.03mg had PCOS, compared to 2.09% of women taking levonorgestrel/ethinyl-estradiol 0.03mg. (unpublished: 2011) Because women with PCOS are known to represent a population at high risk for VTE, this could be a potential issue for previous studies. Do you have data on the prevalence of polycystic ovary syndrome (PCOS) in your study population?

I would appreciate any comments you provide.

References

1. Gronich N, Lavi I, Rennert G. Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population- based cohort study. [published online ahead of print November 7, 2011]. CMAJ. 2011:doi:10.1503/cmaj.110463.

2. Dinger JC, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception. 2007;75:344-354.

3. Eng PM, Seeger JD, Loughlin J, et al. Supplementary data collection with case-cohort analysis to address potential confounding in a cohort study of thromboembolism in oral contraceptive initiators matched on claims-based propensity scores. Pharmacoepidemiol Drug Saf. 2008;17:297 -305.

4. Etminan M, Delaney JA, Bressler B, et al. Oral contraceptives and the risk of gallbladder disease: a comparative safety study. CMAJ 2011;183(8):899-904.

Conflict of Interest:

This letter represents the opinion of the author and not those of the Food and Drug Administration.