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ACE Inhibitors for Stable CAD: Mounting Evidence

Do the benefits of ACE inhibitors extend to patients with stable coronary artery disease?

Angiotensin-converting-enzyme (ACE) inhibitors limit adverse cardiovascular events in heart-failure patients and other patients who are at high risk for ischemic events. Might the benefits of ACE inhibitors extend to patients with stable coronary artery disease (CAD)? In a study supported by a manufacturer of perindopril, European investigators randomized 12,218 patients with stable CAD but without heart failure to perindopril (target dose, 8 mg once daily) or placebo; all subjects received conventional CAD therapy.

At a mean follow-up of 4.2 years, the rate of cardiovascular death, nonfatal myocardial infarction, or cardiac arrest with successful resuscitation was significantly lower among perindopril recipients (8%) than among placebo recipients (10%). Perindopril's benefit was evident even among patients who were taking ß-blockers, lipid-lowering drugs, or calcium-channel blockers, and among diabetic patients. Perindopril lowered blood pressure by an average of 5 mm Hg systolic and 2 mm Hg diastolic. However, improved outcomes were noted both in hypertensive and in normotensive subgroups, which suggested that the benefits were mediated at least partly by mechanisms other than BP lowering.

Comment: These data provide more support for the benefit of ACE inhibitors in CAD patients. As an editorialist notes, these subjects were at lower risk than subjects in the HOPE trial, in which the ACE inhibitor ramipril reduced risk for cardiovascular death, MI, or stroke by 22% over placebo in patients with known cardiovascular disease or diabetes but without heart failure (Journal Watch Jan 25 2000). Precisely how ACE inhibitors achieve their benefit and whether they vary from each other in effectiveness isn't clear, but existing evidence suggests that CAD patients without contraindications should receive ACE inhibitors in addition to standard therapy.

— Kirsten E. Fleischmann, MD, MPH

Published in Journal Watch General Medicine October 21, 2003

Citation(s):

The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: Randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003 Sep 6; 362:782-8.

• Medline abstract (Free)

White HD. Should all patients with coronary disease receive angiotensin-converting-enzyme inhibitors? Lancet 2003 Sep 6; 362:755-7.

• Medline abstract (Free)