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Angiotensin-converting-enzyme inhibition in stable coronary artery disease
Eugene Braunwald1, Michael J Domanski, Sarah E Fowler
1Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Insights
Adding angiotensin-converting-enzyme (ACE) inhibitors to standard therapy did not significantly reduce cardiovascular events in patients with stable coronary artery disease and preserved left ventricular function. This ACE inhibitor trial found no additional benefit beyond current treatments.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Angiotensin-converting-enzyme (ACE) inhibitors are established treatments for heart failure and cardiovascular risk reduction.
- Previous studies indicated potential benefits of ACE inhibitors in patients with vascular disease, even without heart failure.
Purpose of the Study:
- To evaluate the efficacy of adding ACE inhibitors to modern conventional therapy in patients with stable coronary artery disease and normal or mildly reduced left ventricular function.
Main Methods:
- The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial was a double-blind, placebo-controlled study.
- 8290 patients with stable coronary artery disease were randomized to receive either trandolapril (an ACE inhibitor) or a placebo.
Main Results:
- The primary endpoint (cardiovascular death, myocardial infarction, or coronary revascularization) occurred in 21.9% of the trandolapril group versus 22.5% in the placebo group.
- No statistically significant difference was observed between the trandolapril and placebo groups (hazard ratio: 0.96; 95% CI: 0.88 to 1.06).
- Patients in the trial received intensive contemporary treatment, including high rates of prior coronary revascularization and lipid-lowering drug use.
Conclusions:
- In patients with stable coronary heart disease and preserved left ventricular function on current standard therapy, adding an ACE inhibitor (trandolapril) did not provide further significant reduction in cardiovascular events.
- The observed lower event rate in this population, compared to historical trials, suggests that current standard therapies may already offer substantial cardiovascular protection.
Background:
Angiotensin-converting-enzyme (ACE) inhibitors are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure. ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure.
Methods:
In the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial, we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy. The trial was a double-blind, placebo-controlled study in which 8290 patients were randomly assigned to receive either trandolapril at a target dose of 4 mg per day (4158 patients) or matching placebo (4132 patients).
Results:
The mean (+/-SD) age of the patients was 64+/-8 years, the mean blood pressure 133+/-17/78+/-10 mm Hg, and the mean left ventricular ejection fraction 58+/-9 percent. The patients received intensive treatment, with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs. The incidence of the primary end point--death from cardiovascular causes, myocardial infarction, or coronary revascularization--was 21.9 percent in the trandolapril group, as compared with 22.5 percent in the placebo group (hazard ratio in the trandolapril group, 0.96; 95 percent confidence interval, 0.88 to 1.06; P=0.43) over a median follow-up period of 4.8 years.
Conclusions:
In patients with stable coronary heart disease and preserved left ventricular function who are receiving "current standard" therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease, there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes, myocardial infarction, or coronary revascularization.
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