Angiotensin-converting enzyme inhibitors and atherosclerotic plaque: a key role in the cardiovascular protection of patients with coronary artery disease

In EUROPA, the angiotensin-converting enzyme inhibitor (ACEI) perindopril on top of other preventative therapies reduced the risk of major coronary events (cardiovascular death, myocardial infarction, resuscitated cardiac arrest) by 20% when compared with placebo (P = 0.0003) in patients with stable coronary artery disease (CAD). These cardiovascular benefits may be attributable not only to the blood pressure-lowering effect of the drug, but also potentially to a direct cardioprotective vascular effect as determined in two substudies of EUROPA. Analysis of intravascular ultrasound data from the PERSPECTIVE substudy indicated that perindopril treatment may be associated with favourable patterns of coronary remodelling that are associated with plaque stabilization and may induce regression of non-calcified lesions. In the PERTINENT substudy, there were reductions in markers of coronary vascular endothelial cell dysfunction and the rate of endothelial cell apoptosis in perindopril recipients. Experimental data suggest an advantage of perindopril over other ACEIs at the level of tissue ACE inhibition and relative selectivity for bradykinin, which may explain the mechanism of the beneficial effect of perindopril on the endothelium. These differences may underpin the differential results in large clinical trials of ACEIs in patients with stable CAD.