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

Farmer, R.D.T., Lawrenson, R.A., Todd, J.C., Tyrer, F.C., Williams, T.J., MacRae, K.D. and Leydon, G.M. (2000) A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives. British Journal of Clinical Pharmacology, 49 (6), 580-590. (doi:10.1046/j.1365-2125.2000.00198.x).

Abstract

Aims
In October 1995 in response to the results of three studies, the Committee on the Safety of Medicines advised doctors and pharmacists that oral contraceptives containing desogestrel (DSG) and gestodene (GST) were associated 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 users of combined oral contraceptives (COCs), to compare the risk between formulations and to examine the effect of using age banding as opposed to matching by exact year of birth.

Methods
A nested case control study was conducted using the General Practice Research Database. Women with a VTE event recorded between 1992 and 1997, who were treated with an anticoagulant, from consideration of their prescription 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 comparison with the previous studies, two nested case control studies were undertaken. 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 oral contraceptives of 3.8 per 10 000 exposed women years. Incidence rates increased markedly after 35 years of age. The nested case-control study using controls matched by year of birth showed no significant difference in risk between the major COC formulations. With levonorgestrel (LNG) 150 µg and ethinyloestradiol (EE) 30 µg as the reference, the adjusted ORs for GST 75 µg and EE 30 µg was 1.3 (95% CI 0.8, 2.1), for DSG 150 µg and EE 30 µg it was 1.0 (95% CI 0.7, 1.7) and for DSG 150 µg and EE 20 µg 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 mixed group of COCs, characterized by having LNG as the progestogen component was used as the reference category, there was an elevation in the ORs for the 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)) and asthma (OR 1.9 (1.3, 2.9)). The OR for women who had proxy evidence of general 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 characteristics of the women taking COCs affect the risk of VTE. There is no evidence to support the hypothesis that there is any difference in risk between COC formulations containing under 50 µg ethinyloestradiol.

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Contributors

Author: G.M. Leydon

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