Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data
Jick SS,Hernandez RK
Published April 21, 2011BMJ (Clinical Research Ed.), 342(apr21 2), d2151
Jick, S. S., & Hernandez, R. K. (2011). Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ (Clinical Research Ed.), 342(apr21 2), d2151. https://doi.org/10.1136/bmj.d2151
Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ. 2011;342(apr21 2):d2151. doi:10.1136/bmj.d2151
Jick, Susan S., and Rohini K. Hernandez. "Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data." BMJ (Clinical Research Ed.), vol. 342, no. apr21 2, 2011, pp. d2151.
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RRM Academy Synopsis
Drospirenone pills carried about twice the blood clot risk, US study
Drospirenone pill users had about double the odds of a blood clot compared with levonorgestrel pill users. A nested case-control and cohort study of United States claims data matched 186 women with an unexplained clot to 681 without one, all aged 15 to 44. The overall risk stayed low for both groups.
Study at a glance, nested case-control and cohort study: Drospirenone pills carried about twice the blood clot risk, US study. Source: Jick SS et al., 2011, PMID 21511805.
Key Findings
The odds ratio for an unexplained, non-fatal blood clot was 2.3 (95% CI 1.6 to 3.2) among 186 cases and 681 controls, rising to 2.4 (1.7 to 3.4) adjusted for use duration.
The incidence rate was 30.8 (25.6 to 36.8) per 100,000 woman years for drospirenone users and 12.5 (9.61 to 15.9) for levonorgestrel users, an age-adjusted rate ratio of 2.8 (2.1 to 3.8).
Among women under 30, the odds ratio was 3.7 (2.0 to 6.9), rising to 4.0 (2.1 to 7.7) after adjusting for duration of use.
Among women aged 30 to 39 the odds ratio was 1.9 (1.1 to 3.3); among those aged 40 to 44, a smaller age group, it was 1.4 (0.65 to 3.0).
The study drew on 937,408 women contributing 392,844 woman years of drospirenone use and 521,824 woman years of levonorgestrel use, from US claims data spanning 2002 to 2008.
Interpretation
This nested case-control and cohort study drew on a United States claims database covering about 55 million people. Researchers matched 186 women aged 15 to 44 with a newly diagnosed, unexplained clot to 681 women without one, all from the same group of 937,408 birth control users used to calculate clot rates. Matching cases and controls on age and the same calendar date aimed to isolate the pill's own role in risk, and the higher odds held after the authors adjusted for obesity, menstrual disorders and length of use. The authors note that clot diagnoses were not checked against primary medical records, and judged that this would not explain the raised risk. A companion United Kingdom study found a similar effect size. The authors conclude that, in the absence of other considerations, a drospirenone pill should not be the first choice of birth control pill.
RRM Context
This study compares two birth control pills that both suppress a woman's own hormone cycle. NaProTechnology and other cycle-tracking methods read a woman's own hormone signs and add no outside hormones to her body. The clotting difference found here sits inside the hormone-pill category.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel.
Design
Nested case-control and cohort study.
Setting
The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans.
Participants
The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time.
Main Outcome Measures
Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives.
Results
186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100,000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100,000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8).
Conclusions
The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account.
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