The effectiveness of HMG‐CoA reductase inhibitors in an elderly population is independent of apolipoprotein E‐genotypes

Abstract

In a substudy of the Scandinavian Simvastatin Survival Study (4S) subjects with coronary heart disease (aged 35–70 years) with the e4-allele of apoE had nearly twice the risk of dying, compared with patients without an e4-allele. Simvastatin treatment reduced the risk of mortality by 67% in e4 carriers and by 34% in non e4 carriers. The aim of the study was to assess whether the effectiveness of statins in the prevention of myocardial infarction, stroke, and total mortality is influenced by apoE genotype in an elderly population. We used data from the Rotterdam study, a prospective population-based cohort study in the Netherlands, which started in 1990 and included 7,983 subjects aged 55 years and older. We selected patients who were treated with statins at baseline or who had a baseline total cholesterol ≥6.5 mmol l−1. We compared the incidence of myocardial infarction, stroke and total mortality in subjects who received ≥2 years of statin treatment with the untreated subjects by using a Cox proportional hazard model with cumulative statin use as time dependent covariate. At baseline there were 3,813 subjects eligible, seven died before 1-1-1991 and 180 subjects were excluded because of missing apoE genotypes. 3,626 subjects remained for the analyses. The adjusted relative risk of myocardial infarction and stroke was 0.62 (95% CI 0.3, 1.1) for subjects treated with statins for more than 2 years (1148.5 person years) compared with untreated subjects (23252.8 person years). In the subjects treated for less than 2 years (1581 person years) the relative risk was 1.42 (95% CI 1.0, 2.1). The adjusted relative risks for myocardial infarction and stroke were similar for subjects with the e4 allele (0.61, 95% CI 0.2, 2.0) and without the e4 allele (0.63, 95% CI 0.3, 1.3). The adjusted relative risk of mortality from any cause was 0.90 (95% CI 0.6, 1.4) for subjects treated with statins for more than 2 years compared with untreated subjects. The adjusted relative risk of total mortality in subjects with the e4 allele was 1.06 (95% CI 0.5, 2.2) and in subjects without the e4 allele 0.80 (95% CI 0.5, 1.4). We found a non-significant protective effect of statins after 2 years of treatment in all apoE genotypes. In subjects treated for less than 2 years the elevated risk was possibly caused by confounding by indication. There were no differences in the effects of statins on the risks of myocardial infarction and stroke or total mortality between subjects with and without apoE4. This study was financially supported by the Netherlands Heart Foundation, grant number NHF-2000.170.