PEACE Trial Yields Unexpected Findings with Additive ACE Inhibitor Therapy
November 7, 2004 (eshonline.org) – Adding the ACE inhibitor trandolapril to optimal conventional therapy in patients with stable coronary heart disease and preserved left ventricular function did not reduce atherosclerotic-related events in the double-blind, placebo-controlled PEACE (Prevention of Events with Angiotensin Converting Enzyme Inhibition) trial. PEACE was presented at the American Heart Association meeting and simultaneously published by the New England Journal of Medicine (NEJM 2004;351:2058-2068).
PEACE randomized 8290 patients to trandolapril (4158 patients; target dose 4 mg daily) or to matching placebo (4132 patients) and followed for a mean of 4.8 years. The mean age of the patients was 64 years, baseline blood pressures were 133/78, mean left ventricular ejection fraction 58%. A statistically significant difference in the blood pressure reduction between the 2 groups was seen at 36 months (4.4/3.6 mm Hg trandolapril, 1.4/2.4 mm Hg placebo).
The composite primary endpoint of cardiovascular death, myocardial infarction, and coronary revascularization occurred in 21.9% of the trandolapril group and 22.5% of the placebo group (hazard ratio 0.96; p=0.43). The lack of benefit was consistent in all subgroups (age, gender, presence or absence of MI, stroke, diabetes).
The results from the PEACE trial suggest, stated the study presenter, Dr. Marc Pfeffer, Boston, MA, that we may be reaching a time where there is some redundancy in treatment, with little added benefit to taking an additional drug. Hence, in patients with preserved left ventricular function whose global risk is well-treated and well-managed, there may be some room to remove a drug from therapy.
The PEACE Trial
Editorial Comment
Prof. A.M. Heagerty
Editor-in-Chief - Esh Website
The results of the PEACE trial have now been published in full. It tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derived therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy. In this case Trandolapril was compared with placebo. Unlike previous trials of similar design, this study failed to show a difference in terms of death from cardiovascular causes, myocardial infarction or coronary revascularisation in patients administered with the ACE inhibitor compared with placebo. Again like the HOPE trial, which was of similar design, the systolic blood pressure fell by an average of 3mm in patients treated with Trandolapril compared with placebo. This should have been associated with a significant difference in terms of cardiac outcome. When one looks at the data from the HOPE and EUROPA trials, which have shown a positive outcome in the past, one has to say that the patients in the PEACE trial had more intensive management of their other risk factors with substantially more patients in the PEACE trial receiving lipid lowering treatment or having had revascularisation procedures before recruitment into the trial. The authors suggest that the failure to show a difference between placebo and Trandolapril can be explained by the fact that risk modification has been substantially achieved in advance of adding the drug on, which seems entirely justified from the data provided. The outcome should not deter us from aggressively treating these patients and in this context there are data clearly suggesting that newer drugs that block the renin angiotensin system or calcium channels have a prominent role to play. |
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