A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives

Aims In October 1995 in response to the results of three studies, the Commi ttee on the Safety of Medicines advised doctors and pharmacists that oral c ontraceptives containing desogestrel (DSG) and gestodene (GST) were associa ted with around a two-fold increase in the risk of thromboembolism compared with those containing other progestogens. The objective of this study was to estimate the risk of idiopathic venous thromboembolic disease (VTE) in u sers of combined oral contraceptives (COCs), to compare the risk between fo rmulations and to examine the effect of using age banding as opposed to mat ching by exact year of birth. Methods A nested case control study was conducted using the General Practic e Research Database. Women with a VTE event recorded between 1992 and 1997, who were treated with an anticoagulant, from consideration of their prescr iption records were likely to have been using a COC prescription on the day of the event and also had no exclusion factors, were deemed cases. For com parison with the previous studies, two nested case control studies were und ertaken. Study 1 used controls matched by practice and year of birth. Study 2 used controls matched by practice and within 5 years age bands. Results We found an incidence of idiopathic VTE amongst users of combined o ral contraceptives of 3.8 per 10 000 exposed women years. Incidence rates i ncreased markedly after 35 years of age. The nested case-control study usin g controls matched by year of birth showed no significant difference in ris k between the major COC formulations. With levonorgestrel (LNG) 150 mu g an d ethinyloestradiol (EE) 30 mu g as the reference, the adjusted ORs for GST 75 mu g and EE 30 mu g was 1.3 (95% CI 0.8, 2.1), for DSG 150 mu g and EE 30 mu g it was 1.0 (95% CI 0.7, 1.7) and for DSG 150 mu g and EE 20 mu g it was 0.8 (95% CI 0.4, 1.6). Using less rigorous matching criteria, matching controls to cases within 5 years age bands, the ORs increased. When a mixe d group of COCs, characterized by having LNG as the progestogen component w as used as the reference category, there was an elevation in the ORs for th e newer products. We found a significant association between idiopathic VTE and current smoking (OR 2.0 (1.4, 2.7)), BMI over 35 (OR 3.8 (1.8, 8.0)) a nd asthma (OR 1.9 (1.3, 2.9)). The OR for women who had proxy evidence of g eneral ill health (indicated by the number of prescriptions issued) was 2.2 (1.7, 3.7). Conclusions The results of this study indicate that a number of the charact eristics of the women taking COCs affect the risk of VTE. There is no evide nce to support the hypothesis that there is any difference in risk between COC formulations containing under 50 mu g ethinyloestradiol.