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PEACE

25 juin 2016

Prevention of Events with Angiotensin Converting Enzyme Inhibition.

L’étude PEACE? au design proche de celui de l’étude EUROPA? a inclus 8290 patients coronariens stables recevant un IEC? (trandolapril 4 mg/j) comparé à un placebo avec un suivi de 4.8 ans. Aucune différence n’a été observée sur le critère primaire d’évaluation. Le résultat négatif de cet essai, à la différence d’EUROPA, suggère que le bénéfice apporté par l’adjonction d’un IEC peut être limité chez les patients à risque? de décès cardiovasculaire moindre dont le traitement a été optimisé par une plus grande fréquence de la revascularisation et un recours plus large à l’utilisation des statines.

Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL ; PEACE? Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med. 2004 ;351(20):2058-68 15531767

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.

Solomon SD, Rice MM, A Jablonski K, Jose P, Domanski M, Sabatine M, Gersh BJ, Rouleau J, Pfeffer MA, Braunwald E ; Prevention of Events with ACE inhibition (PEACE?) Investigators. Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE?) trial. Circulation. 2006 ;114(1):26-31 16801465

BACKGROUND :
Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.

METHODS AND RESULTS :
We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE?). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE? was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60>
 ; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR?, 0.94 ; 95% CI, 0.78 to 1.13).

CONCLUSIONS :
Although trandolapril did not improve survival in the overall PEACE? cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.