A large observational cohort study has found that use of combined oral contraceptive pills (COCP) containing levonorgestrel with 20 µg of oestrogen was associated with the lowest risk of pulmonary embolism (PE) and arterial thromboembolic events.

The French healthcare system collects data on drugs prescribed, demographic factors, and hospital admission diagnoses. Using this data for a 27-month period, from July 2010 to September 2012, the authors identified 4.9 million women who had been prescribed a COCP, yielding

5.4 million women years of use.

Overall 3,253 serious events were recorded in COCP users; 1,800 PE, 1,046 ischaemic strokes (CVA),

and 407 myocardial infarctions (MI). The absolute risk rates were 33, 19 and 7 per 100,000 women years of COCP use respectively.

More than half (56.7%) of the events occurred among the 26.1% of users who were over 35 years of age.

After controlling for progestogen type and available demographic data (age and socioeconomic status, hypertension and diabetes) users of 20 µg pills had a lower event risk compared with 30-40 µg pills. Adjusted relative risk (RR) for:

• PE, RR 0.75 (95% CI: 0.67-0.85)

• CVA, RR 0.82 (95% CI: 0.70-0.96)

• MI, RR 0.56 (95% CI: 0.39-0.79)

After controlling for oestrogen dose and available demographic data,

a lower event risk was found for levonorgestrel formulations compared with those containing desogestrel or gestodene. Compared with levonorgestrel RR of PE with desogestrel or gestodene formulations was 2.16 (95% CI: 1.93-2.41) and 1.63 (95% CI: 1.34-1.97) respectively.

Cohort observational studies such as this can only show associations, but given the large number of women observed the results do carry some weight. This is despite the lack of data on BMI and smoking for example. Nevertheless, PE appeared to be the most common of the three serious events observed and was associated with both higher oestrogen and third generation COCPs. CVA and MI were very uncommon in this cohort but an association with higher oestrogen dose COCPs was shown.

I took several messages away from this study. COCPs appear to be remarkably safe with very low absolute numbers of venous and arterial thromboembolic events.

Levonorgestrel containing formulations may be a slightly safer option than the newer progestogen formulations in terms of PE. When prescribing COCPs to over 35 year olds, I will use a 20 µg formulation unless there is a compelling reason not to.

Dr Chris Barclay

Weill A, Dalichampt M, Raguideau F et al. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study. BMJ 2016;353:i2002