Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: The Genetics of Hypertension-Associated Treatment (GenHAT) study

Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Utrecht, Utrecht, Netherlands
American heart journal (Impact Factor: 4.46). 02/2007; 153(1):54-8. DOI: 10.1016/j.ahj.2006.10.019
Source: PubMed


The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with pravastatin to modify the risk of coronary heart disease (CHD) and other cardiovascular end points in a large clinical trial.
GenHAT is an ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants randomly assigned to pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin in reducing the risk of primary outcome (all-cause mortality) and secondary outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart failure) was compared between the genotype strata (dominant model ID + II vs DD, additive model II vs ID vs DD), by examining an interaction term in a Cox proportional hazards model.
The relative risk of fatal CHD and nonfatal myocardial infarction among subjects randomized to pravastatin compared with subjects randomized to usual care was similar in subjects with the II genotype (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68-1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27).
We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events.

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Available from: Anke-Hilse Maitland-van der Zee, Oct 03, 2015
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    • "Although this is a positive step, research to identify and validate pharmacogenomic markers of differential statin therapeutic effect has received much greater attention. In comparison, at least 10 pharmacogenomic substudies of statin RCTs have assessed markers of efficacy [Ference et al. 2011; Hoffmann et al. 2011; Maitland-van der Zee et al. 2007]. "
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    • "Regarding clinical outcomes, three randomized trials failed to show any significant ACE genotype-statin treatment interactions in primary [68] or secondary prevention [70,71] of CAD (Additional file 1). Additionally, in the observational Rotterdam study, non-significant associations were reported overall, although a significant interaction between the ACE gene and the use of statins was observed in male participants [69]. "
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