QResearch

​Combined oral contraceptives and risk of venous thromboembolism.

Title

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

What is the aim of the study and why is it important?

Combined oral contraceptives (commonly known as “the pill”) are used by millions of women around the world to prevent pregnancy. As with all medicines, they have side-effects many of which are mild. However one side effect can be an increased risk of thrombosis (“blood clots”) which can be serious and occasionally fatal. New types of pill have been developed using different components (particularly one of the hormones known as progesterone) to reduce the side effects. Whilst there have been studies to compare the risk of blood clots with different types of contraceptive pill, these were done some years ago before there was enough data available to be confident of the results.  We therefore carried out an extremely large study to compare the different types of contraceptive pill used in the UK.

How is the research being done?

We did the study using the two largest UK primary care research databases – QResearch and CPRD.  In total, about 10,000 women between the ages of 15 and 49 were diagnosed with a blood clot between 2001 to 2013.  Each such woman was matched with up to five women of the same age and from the same practice, who had not had a blood clot.  We then estimated the risk associated with different types of oral contraceptive pill, taking into account possible differences in the women’s health or lifestyle by adding all known or possibly relevant factors for which data was available.  These included obesity, smoking history, ethnicity, various long standing diseases and more recent health conditions.

Chief Investigator

Julia Hippisley-Cox

Location of research

Nottingham

Date on which research approved

20-Jun-2014

Project reference ID

R68

Are all data accessed are in anonymised form?

Yes

Brief summary of the dataset to be released (including any sensitive data)

women aged 15-49 with a diagnosis of thrombosis (cases) on GP, hospital or mortality records, matched to controls without thrombosis. GP data included diagnoses, risk factors for thrombosis, relevant prescriptions for oral contraceptive, oral anticoagulants. See protocol for full details.

What were the main findings?

The study found an overall three-fold increased risk of blood clots in women using combined oral contraceptives, but the risks for the different types of oral contraceptive appeared as two distinct groups.  Newer types of pill, which contain gestodene, desogestrel, drospirenone or cyproterone, were associated with risks between 1.5 and 1.8 times higher than either the older types, which contain norethisterone or levonorgestrel, or the relatively newer norgestimate.  In absolute terms, on average only 1 in 766 women taking the newest progestogen, drospirenone, is likely to be diagnosed with a blood clot during a year, while, for the older levonorgestrel, this would drop to 1 in 1739. These risks are likely to be lower than the risk of getting a blood clot during pregnancy.

Implications and Impact

Overall, blood clots are an uncommon side-effect of the Pill, but they are serious and the risk is lower with some types of pill than others. So  doctors need to consider each woman’s health issues and circumstances when prescribing these drugs to assess the pros and cons.  Women using a type of Pill associated with a higher risk of blood clots should consult their doctor and review their current type of pill at their next appointment if they have concerns.

Funding Source

Unfunded

Research Team

Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox: University of Nottingham

Publications

  • Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases
    Authors: Vinogradova Y, Coupland C, Hippisley-Cox J.
    Ref: BMJ 2015;350:h2135
    http://www.bmj.com/content/bmj/350/bmj.h2135.full.pdf
  • Re: Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases
    Authors: Vinogradova Y, Coupland C, Hippisley-Cox J
    Ref: BMJ 2015;350:h2135 Rapid Responses
    https://www.bmj.com/content/350/bmj.h2135/rr-7
  • Combined oral contraceptives and venous thromboembolism. Authors' reply to Zagarella
    Authors: Vinogradova Y, Coupland C, Hippisley-Cox J
    Ref: BMJ 2015;350:h3308
    https://www.bmj.com/content/350/bmj.h3308

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