Adding ACE inhibitor doesn't improve outcomes in stable angina and normal LVEF

Journal of Family Practice, Feb, 2005

* CLINICAL QUESTION

Does adding an angiotensin-converting enzyme inhibitor improve outcomes among patients with stable angina and no evidence of heart failure?

* BOTTOM LINE

Adding the angiotensin-converting enzyme (ACE) inhibitor trandolapril (Mavik) to standard medical treatment of patients with stable angina and normal left ventricular function did not reduce their risk of adverse cardiovascular outcomes. Although higher-risk patients and those with less well controlled risk factors may still benefit from this intervention, this study didn't assess those groups. (LOE=1b)

* STUDY DESIGN

Randomized controlled trial (double-blinded)

* ALLOCATION

Concealed

* SETTING

Outpatient (any)

* SYNOPSIS

The HOPE and EUROPA trials found that ACE inhibitors improve cardiovascular outcomes in patients with vascular disease but with no evidence of overt heart failure. This study attempted to extend these findings to an even lower-risk group using the ACE inhibitor trandolapril (Mavik). The researchers recruited patients older than 50 years with documented coronary artery disease and a left ventricular ejection fraction (LVEF) >40%, excluding patients in poor health, with renal failure, recent unstable angina, or who had recently used an ACE inhibitor. Only patients who tolerated the active drug during a run-in phase were allowed into the study, a step that increases the likelihood of finding a benefit for the drug. The mean age of participants was 65 years, 18% were women, 55% had had a myocardial infarction (MI), 92% were white, and 17% had diabetes. Patients were randomized (allocation concealed) to trandolapril 2 mg per day, increased to 4 mg per day if tolerated, or matching placebo.

Outcomes were blindly assessed and analysis was by intention to treat. The primary outcome began as death or nonfatal MI, but was expanded to include coronary revascularization as a way to reduce sample size and save money halfway through the study. The final sample included 4158 in the trandolapril group and 4132 in the placebo group; patients were followed for a median of 4.8 years. During the study, the safety monitoring committee recommended that all diabetic patients with microalbuminuria be given an ACE inhibitor, effectively removing them from the study. Removing data for these patients did not affect the overall study results.

Much to the investigators' surprise, there was no difference between groups regarding the primary outcome (21.9% in the trandolapril group vs 22.5% in the placebo group) at the end of the study. They hypothesize that this is due to the lower overall risk of the patients in the PEACE study compared with those in the HOPE and EUROPA trials. Certainly, when patients are at greater risk of bad outcomes, they tend to benefit more from interventions, so this argument may have merit. Another explanation is that trandolapril is less effective than ramipril (HOPE) or perindopril (EUROPA), although the extent of blood pressure lowering (3 mm) was similar to that in the HOPE and EUROPA studies.

PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004; 351:2058-2068.