The risk of myocardial infarction in patients with reduced activity of cytochrome P450 2C9

Objective The aim of the present follow-up study was to investigate whether the enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated with myocardial infarction. Methods We investigated whether the variant alleles CYP2C9*2 and CYP2C9*3 or the use of CYP2C9 substrates or inhibitors was associated with an increased risk of myocardial infarction in 2210 men and 3534 women from the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years or older. Results In women, the use of CYP2C9 substrates or inhibitors was significantly associated with incident myocardial infarction with a hazard ratio of 2.48 (95% confidence interval: 1.55–3.96). Within the group of female carriers of a variant allele, the use of CYP2C9 substrates or inhibitors was associated with a fourfold increased risk of myocardial infarction (hazard ratio 3.86, 95% confidence interval: 1.93–7.75), as compared with non-use. Neither the use of CYP2C9 inhibitors or substrates nor the variant CYP2C9 alleles were associated with an increased risk of myocardial infarction in men. Conclusions Drugs that are metabolized by CYP2C9 increase the risk of myocardial infarction in women. This risk was even higher in women with allelic variants of CYP2C9 with reduced enzyme activity.

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