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


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 epsilon4 carriers and 2750 (83.2%) were non-epsilon4 carriers. No significant difference in terms of mortality was observed between the epsilon4 and the non-epsilon4 carriers (3.61% vs. 3.24%, P = 0.67). However, although in non-epsilon4 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 epsilon4 carriers a significant reduction in mortality was observed in patients treated compared with non-treated (1.85% vs. 5.28%, P = 0.023).


CONCLUSIONS
We found that epsilon4 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 epsilon4 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.
Chiodini
Benedetta D
BD
Division of Genetics and Molecular Medicine, King's College London, London, UK.
Franzosi
Maria Grazia
MG
Barlera
Simona
S
Signorini
Stefano
S
Lewis
Cathryn M
CM
D'Orazio
Andria
A
Mocarelli
Paolo
P
Nicolis
Enrico
E
Marchioli
Roberto
R
Tognoni
Gianni
G
D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin