Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research DatabaseBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2139 (Published 21 April 2011) Cite this as: BMJ 2011;342:d2139
- Lianne Parkin, senior lecturer in epidemiology1,
- Katrina Sharples, senior lecturer in biostatistics1,
- Rohini K Hernandez, epidemiologist2,
- Susan S Jick, director2
- 1Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand
- 2Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, 11 Muzzey Street, Lexington, MA 02421, USA
- Correspondence to: S S Jick
- Accepted 24 March 2011
Objective To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel.
Design Nested case-control study.
Setting UK General Practice Research Database.
Participants Women aged 15-44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009. Cases were women with a first diagnosis of venous thromboembolism; up to four controls, matched by age, duration of recorded information, and general practice, were randomly selected for each case.
Main outcome measures Odds ratios and 95% confidence intervals estimated with conditional logistic regression; age adjusted incidence rate ratio estimated with Poisson regression.
Results 61 cases of idiopathic venous thromboembolism and 215 matched controls were identified. In the case-control analysis, current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use; the odds ratio adjusted for body mass index was 3.3 (95% confidence interval 1.4 to 7.6). Subanalyses suggested that referral, diagnostic, first time user, duration of use, and switching biases were unlikely explanations for this finding. The crude incidence rate was 23.0 (95% confidence interval 13.4 to 36.9) per 100 000 woman years in current users of drospirenone and 9.1 (6.6 to 12.2) per 100 000 woman years in current users of levonorgestrel oral contraceptives. The age adjusted incidence rate ratio was 2.7 (1.5 to 4.7).
Conclusions These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.
We thank David Skegg and Charlotte Paul for their helpful comments on an earlier draft of the paper and Sheila Williams for help with implementing multiple imputation methods in Stata.
Contributors: LP was involved in the conception, design and conduct of the study, contributed to the analyses, interpreted the results, and wrote the manuscript. SSJ was involved in the conception and design of the study, obtained data for and oversaw the conduct of the study, and contributed to the interpretation of the results and the writing of the manuscript. KS did the imputed data analyses, interpreted the results, and contributed to the manuscript. RKH contributed to the conduct of the analyses, the interpretation of the results, and the manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. SSJ is the guarantor.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The protocol for this study was approved by the Independent Scientific Advisory Committee for MHRA (Medicines and Healthcare Products Regulatory Agency) database research.
Data sharing: If access to the source data used for this study is required, please contact the data owner at.
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