Third generation oral contraceptives and risk of myocardial infarction: an international case-control study

Abstract

<h3>Abstract</h3> <b>Objective</b>: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of myocardial infarction. <b>Design</b>: Matched case-control study. <b>Setting</b>: 16 centres in Austria, France, Germany, Switzerland, and the United Kingdom. <b>Subjects</b>: 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. <b>Main outcome measures</b>: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. <b>Results</b>: 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&lt;0.001). <b>Conclusion</b>: 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. <h3>Key messages</h3> Key messages Compared with the results of British studies published in the 1970s, the risk of myocardial infarction among current users v non-users of second generation oral contraceptives was low The risk of myocardial infarction was appreciably lower among women using third generation products, the risk being comparable to that among women who did not use oral contraception and two to three times lower than that among women using second generation products The results suggest that about 12 fewer deaths from myocardial infarction in England and Wales and 46 fewer in Germany would occur each year if all those taking second generation oral contraceptives started taking third generation products Both the risks and the benefits of oral contraceptives need to be considered in a balanced way so that doctors can give judicious advice and women have informed choice