Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: The GISSI-Prevenzione study

Aims: Controversy exists with regard to the influence of APOE polymorphisms on coronary heart disease development and on the efficacy of statin treatment. We investigated the relationship between APOE, mortality and the response to treatment in Mediterranean myocardial infarction (MI) survivors. Methods and results: We analysed 3304 Italian patients with MI randomized to pravastatin or no treatment in the GISSI-Prevenzione study, with a mean follow-up time of 23.0 ± 6.7 months (median 24.3 months). Mortality curves were calculated using Kaplan-Meier method, and differences in survival were tested using the log-rank test. There were 109 deaths during follow-up. Patients treated with pravastatin showed a significant decrease in mortality compared with non-treated patients (HR 0.67, 95% confidence interval 0.45-0.97, P = 0.038). Among the 3304 patients, 554 (16.8%) were ε4 carriers and 2750 (83.2%) were non-ε4 carriers. No significant difference in terms of mortality was observed between the ε4 and the non-ε4 carriers (3.61% vs. 3.24%, P = 0.67). However, although in non-ε4 carriers no significant difference in mortality was observed between patients treated with pravastatin and non-treated (2.81% vs. 3.67%, P = 0.21), among the ε4 carriers a significant reduction in mortality was observed in patients treated compared with non-treated (1.85% vs. 5.28%, P = 0.023). Conclusion: We found that ε4 allele is a determinant of pravastatin response in terms of survival. Though in the entire population investigated,we found a beneficial effect of pravastatin in terms of survival, only the ε4 carriers seemed to have gained a significant benefit from this treatment. We suggest that the effect of statins is of particular interest in this fraction of the population. Genetic markers can help in identifying patients that benefit more from statin treatment.