European Heart Journal Advance Access published online on June 13, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm196
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Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study
1 Division of Genetics and Molecular Medicine, King's College London, London, UK
2 Department of Cardiovascular Research, ‘Mario Negri’ Institute for Pharmacological Research, Via Eritrea, 20157 Milano, Italy
3 University Department of Laboratory Medicine, Hospital of Desio, Milano, Italy
4 University of Milano-Bicocca, Medical School DMS, Milano, Italy
5 Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
Received 15 December 2006; revised 13 April 2007; accepted 18 April 2007.
* Corresponding author. Tel: +39 0 239014482; fax: +39 0 233200049. E-mail address: franzosi{at}marionegri.it
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 
4 carriers and 2750 (83.2%) were non-4 carriers. No significant difference in terms of mortality was observed between the 4 and the non-4 carriers (3.61% vs. 3.24%, P = 0.67). However, although in non-4 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 4 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 4 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 4 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.
Key Words: Myocardial infarction • Genetics • Apolipoproteins • Survival • Pharmacogenetics • Statins
A complete list of GISSI-Prevenzione study committees, collaborators, and participating centers was published in The Lancet (1999; 354:447–455).