Combined oral contraceptives containing drospirenone appear to carry a three-fold higher risk of non-fatal idiopathic venous thromboembolism (VTE) than those containing levonorgestrel, although the overall risk is still low.

The study used data from the UK General Practice Research Database (GPRD) that gathers information from a large number of general practices and more than three million people in the UK, including demographic data, information about prescribed drugs, diagnoses, hospital admissions and deaths.

Women, aged 15-44 years, who had a recorded diagnosis of non-fatal idiopathic VTE (deep vein thrombosis or pulmonary embolism) and were current users of an oral contraceptive containing 30 µg oestrogen combined with drospirenone or levonorgestrel were studied. Up to four controls were randomly selected for each case; matched by age, duration of recorded information and general practice.

The study period was from May 2002 to September 2009. In total 65 potentially eligible cases of VTE were identified of which 61 were confirmed. There were 215 matched controls. Mean age was 32.2 years for cases and 31.8 for controls.

The case-control analysis revealed that current use of a drospirenone-containing contraceptive was associated with a three-fold higher risk of non-fatal idiopathic VTE compared with levonorgestrel; the odds ratio adjusted for BMI was 3.3 (95% CI: 1.4 to 7.6). It must be stressed that the crude incidence for VTE was still low in both groups: 23.0 (95% CI: 13.4 to 36.9) per 100,000 woman-years in current users of drospirenone compared with 9.1 (95% CI: 6.6 to 12.2) per 100,000 woman-years of levonorgestrel use.

Confounding by age, BMI, smoking, concomitant drug use or underlying medical conditions was unlikely. Although information about family history was incomplete, the authors concluded this was unlikely to explain a three-fold increase in risk.

The low numbers of cases and some missing demographic data are the main weaknesses of the paper. Many other studies appear to show similar, albeit weak, association between drospirenone and VTE risk. One of these studies is by two of the authors of this paper, in the same issue, and showed a two-fold increase in risk of VTE in users of drospirenone.¹

Sensible and pragmatic advice comes from an accompanying editorial: as the absolute risk of VTE due to drospirenone is still inconclusive, an individualised risk-benefit assessment should be carried out and the pill with the best safety profile should be considered first.²

Dr Richard Ma

• Parkin L, Sharples K, Hernandez RK et al. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database BMJ 2011;340:d2139