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. 2015 May 26:350:h2135.
doi: 10.1136/bmj.h2135.

Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

Yana Vinogradova  1 , Carol Coupland  2 , Julia Hippisley-Cox  2
Affiliations

Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

Yana Vinogradova et al. BMJ. .

Abstract

Objective: To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account.

Design: Two nested case-control studies.

Setting: General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices).

Participants: Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year.

Main outcome measures: Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets.

Results: 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10,000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17).

Conclusions: In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any additional organisation for the submitted work; JHC is professor of clinical epidemiology at the University of Nottingham and unpaid director of QResearch, a not-for-profit organisation which is a joint partnership between the University of Nottingham and EMIS (commercial IT supplier for 60% of general practices in the UK); JHC is also a paid director of ClinRisk, which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk algorithms within clinical computer systems to help improve patient care; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow of included patients for CPRD and QResearch analyses with proportions of excluded observations at each point of exclusion
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Fig 2 Use of different types of oral contraceptives by year and database. Data are based on age standardised exposure in controls using the UK’s general population
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Fig 3 Adjusted odds ratio for VTE in patients currently exposed to combined oral contraceptives compared with no use in the last year, by database. Odds ratios and 95% confidence intervals are adjusted for body mass index, smoking status, alcohol consumption, ethnic group, chronic and acute conditions, and use of other hormonal contraceptives
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