Third Generation Oral Contraceptives and Risk of Myocardial Infarction: an International Case-control Study. Transnational Research Group on Oral Contraceptives and the Health of Young Women

Objective: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of myocardial infarction.

Design: Matched case-control study.

Setting: 16 centres in Austria, France, Germany, Switzerland, and the United Kingdom.

Subjects: Cases were 153 women aged 16-44 with a myocardial infarction event. Controls were 498 women (at least 3 controls per case) unaffected by myocardial infarction who were matched with their corresponding case for age and for hospital or community setting within four months of the index infarction.

Main Outcome Measures: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables.

Results: The estimated odds ratio for myocardial infarction of third compared with second generation oral contraceptives among all 651 study subjects was 0.36 (95% confidence interval 0.1 to 1.2) (P = 0.11). The odds ratio for the United Kingdom and Germany alone was 0.45 (0.1 to 1.8) (P = 0.26). Other odds ratios for the five countries were 3.1 (1.5 to 6.3) (P = 0.003) for use of second generation products v no current use and 1.1 (0.4 to 3.4) (P = 0.9) for use of third generation products v no current use. Among the confounding variables the independent contribution of smoking (for which adjustment was made in the above estimates) proved to be important (10.1 (5.7 to 17.9), P < 0.001).

Conclusion: An odds ratio of 0.45 with wide confidence intervals shows that third generation oral contraceptives compared with second generation products are associated with a reduced risk of myocardial infarction or with no difference. This finding from an interim analysis should be interpreted with extreme caution. However, the excess risk of venous thromboembolism associated with the use of third generation products may be balanced by the reduced risk of myocardial infarction associated with the same products.