The apolipoprotein epsilon 4 allele determines prognosis and the effect onprognosis of simvastatin in survivors of myocardial infarction - A substudy of the Scandinavian Simvastatin Survival Study

Background-Carriers of the epsilon 4 allele of the apolipoprotein E gene ar e at a higher risk of coronary heart disease than individuals with other ge notypes, We examined whether the risk of death or a major coronary event in survivors of myocardial infarction depended on apolipoprotein E genotype a nd whether the benefits of treatment with simvastatin differed between geno types. Methods and Results-Cox proportional hazards models were used to analyze 5. 5 years of follow-up data from 966 Danish and Finnish myocardial infarction survivors enrolled in the Scandinavian Simvastatin Survival Study. A total of 16% of the 166 epsilon 4 carriers in the placebo group died compared wi th 9% of the 312 patients without the allele, which corresponds to a mortal ity risk ratio of 1.8 (95% confidence interval, 1.1 to 3.1). The risk ratio was unaffected by considerations of sex, age, concurrent angina, diabetes, smoking, and serum lipids in multivariate analyses. Simvastatin treatment reduced the mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in epsilon 4 carriers and to 0.66 (95% confidence interval, 0.35 to 1.24) i n other patients (P=0.23 for treatment by genotype interaction). Apolipopro tein E genotype did not predict the risk of a major coronary event. Baselin e serum levels of lipoprotein(a) also predicted mortality risk and could be combined with epsilon 4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment. Conclusions-Myocardial infarction survivors with the epsilon 4 allele have a nearly 2-fold increased risk of dying compared with other patients, and t he excess mortality can be abolished by treatment with simvastatin.