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New Trial of ACE Inhibition in Stable Coronary Disease

In a placebo-controlled trial, trandolapril did not improve outcomes among patients with stable CAD and no evidence of heart failure.

In two recent international trials, HOPE and EUROPA, angiotensin-converting-enzyme (ACE) inhibitors reduced morbidity and mortality in patients with stable coronary artery disease (or multiple CAD risk factors) and without heart failure (Journal Watch Jan 25 2000 and Journal Watch Oct 21 2003 ). Now we have a third study, the PEACE trial, which was partially industry-supported and conducted mainly in North America.

Researchers randomized 8290 patients with stable CAD and normal left ventricular ejection fractions (mean, 58%) to receive trandolapril (target, 4 mg daily) or placebo. At baseline, mean blood pressure was 134/78 mm Hg, 70% of subjects were taking lipid-lowering drugs, and 72% had undergone percutaneous coronary intervention or bypass surgery.

At a median follow-up of 5 years, the incidence of the primary endpoint (death from cardiovascular causes, nonfatal myocardial infarction, or coronary revascularization) was not significantly different between the trandolapril and placebo groups (21.9% and 22.5%). No subgroup benefited from trandolapril. Trandolapril lowered mean systolic blood pressure by 3 mm Hg more than placebo did.

Comment: Surprisingly, the ACE inhibitor trandolapril did not improve outcomes among patients with stable CAD and no evidence of heart failure. The authors and editorialist speculate about why this result differs from findings of other trials. One plausible reason is that PEACE involved lower-risk patients: Cardiovascular event rates were lower in the PEACE placebo group than in the HOPE and EUROPA placebo groups, possibly because a greater proportion of PEACE subjects were using statins and had undergone previous coronary revascularization. Another possibility is that not all ACE inhibitors are equally effective. The authors and editorialist conclude that ACE-inhibitor therapy is not mandatory in selected low-risk CAD patients.

— Allan S. Brett, MD

Published in Journal Watch General Medicine November 19, 2004

Citation(s):

The PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004 Nov 11; 351:2058-68.

• Medline abstract (Free)

Pitt B. ACE inhibitors for patients with vascular disease without left ventricular dysfunction -- May they rest in PEACE? N Engl J Med 2004 Nov 11; 351:2115-7.

• Medline abstract (Free)

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