The objective of this study was to assess the risk of myocardial infarction (MI) associated with the use of new and old combination oral contraceptives (OC). A matched case-control study in 16 centers in Germany, the United Kingdom, France, Austria, and Switzerland explored the association of current use of combination OC with the occurrence of MI. Our subjects were 182 women aged 16-44 years with MI; the controls were 635 women without MI (at least one hospital control and one community control per case) matched for 5-year age group and region. The main outcome measures were odds ratios comparing current use of a specific group of OC against current use of other groups or against no current use. The adjusted overall odds ratio (OR; 95% confidence intervals) for MI for second generation OC versus no current use was 2.35 (1.42 to 3.89) and 0.82 (0.29 to 2.31) for third generation OC (low dose ethinyl estradiol, gestodene, and desogestrel). A direct comparison of third generation users with second generation users yielded an OR of 0.28 (0.09 to 0.86). In subgroup analyses, the odds ratio for the UK alone was 1.25 (0.36 to 4.29), while for continental Europe it was 0.10 (0.02 to 0.48). For hospital controls, the risk estimated was 0.98 (0.22 to 4.44), and 0.18 (0.04 to 0.65) for community controls. The independent risk of MI among current smokers adjusted for OC use was 7.21 (4.58 to 11.36). Among users of third generation OC, the OR for current smokers was 3.75 (0.65 to 21.74) and among users of second generation it was 9.50 (2.93 to 30.96). A comparison of OC use in the UK for the time before and after regulatory action was taken in October 1995 shows that the likelihood of a control (last control accrued June 1996) being treated with second generation OC is seven times higher after 1 November 1995 than it was before. Third generation OC are the first to be associated with no excess risk of MI. A significantly lower risk of MI is found when comparing use of third generation OC with use of second generation OC. There seems to be an impressive amelioration of risk among smokers using newer OC. An impact of regulatory action in the UK was found in the OC use spectrum of controls.
PIP: The risk of myocardial infarction associated with use of second- and third-generation oral contraceptives (OCs) was investigated in a matched case-control study conducted at 16 centers in Germany, the UK, France, Austria, and Switzerland. 182 women 18-44 years old with myocardial infarction were matched for 5-year age group and region with 635 controls (at least 1 hospital control and 1 community control per case). 57 cases and 156 controls reported exposure to OCs, of whom 7 cases and 49 controls had taken third-generation formulations. The adjusted overall odds ratio (OR) for myocardial infarction was 2.35 (95% confidence interval [CI], 1.42-3.89) for second-generation OC use versus no use but only 0.82 (95% CI, 0.29-2.31) for third-generation OC use versus no use. A direct comparison of third-generation and second-generation OC users yielded an OR of 0.28 (95% CI, 0.09-0.86). 80% of cases, compared with 37% of controls, were current smokers. The independent risk of myocardial infarction among current smokers adjusted for OC use was 7.21 (95% CI, 4.58-11.36). The OR for current smokers was 3.75 (95% CI, 0.65-21.74) among users of third-generation OCs and 9.50 (95% CI, 2.93-30.96) among users of second-generation formulations. These Transnational Study findings indicate that third-generation formulations are the first OCs to be associated with no excess risk of myocardial infarction; moreover, they substantially reduce this risk among smokers. The reduced risk of myocardial infarction associated with OCs containing desogestrel and gestodene compared with levonorgestrel may reflect the failure of third-generation progestins to inhibit the estrogen-related increase in sex hormone binding globulin.