World Congress

ACE-Inhibitors

An overview of clinical trials, including approximately 42,000 patients, led researchers to conclude that angiotensin-converting enzyme (ACE)-inhibitors should be considered for all patients with evidence of vascular atherosclerotic disease.

The meta-analysis, conducted by Gilles R. Dagenais, MD, at Laval University Heart and Lung Institute, Laval Hospital, in Quebec, Canada, looked at three trials of ACE-inhibitors among patients with stable vascular disease without left ventricular systolic dysfunction or heart failure:

  • HOPE – ramipril canadian: Heart Outcomes Prevention Evaluation
  • EUROPA – canadian perindopril: European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease
  • PEACE-trandolapril (Mavik): Prevention of Events with

ACE Inhibition

Dr. Dagenais then evaluated five other studies of ACE-inhibitors in patients with heart failure and left ventricular systolic dysfunction (LVSD):

  • SOLVD-T: Studies Of Left Ventricular Dysfunction Treatment
  • SOLVD-P: Studies Of Left Ventricular Dysfunction Prevention
  • SAVE: Survival and Ventricular Enlargement
  • AIRE: Acute Infarction Efficacy
  • TRACE: Trandolapril Cardiac Evaluation

Among the first three trials, only PEACE did not meet its primary outcome: a 4% relative risk reduction in death from cardiovascular disease, nonfatal myocardial infarction (MI), or coronary revascularization (P = .043).

Patient populations in the HOPE, EUROPA and PEACE trials, which together included nearly 30,000 patients, were generally similar, except for age, blood pressure (BP), and diabetes rates, which were higher in HOPE. More patients in the PEACE trial received lipid-lowering agents, but more patients in PEACE also had undergone percutaneous coronary intervention or coronary artery bypass graft surgery.

In EUROPA, PEACE, and HOPE, all-cause mortality rates for ACE-inhibitors, compared with placebo, were 6.1% versus 6.9%, 7.2% versus 8.1%, and 10.4°% versus 12.2°%, respectively. Results across all eight trials were consistent in revealing reduced all-cause mortality for ACE-inhibitors compared with placebo.

The overall all-cause mortality odds ratio (OR) for ACE-inhibitors in the three trials without heart failure or LVSD was 0.86; the odds ratio for those with heart failure was 0.80.
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Among the 12 trials, only PEACE did not show a reduction in nonfatal MI. Stroke was reduced in the EUROPA, PEACE and HOPE trials (OR, 0.77) but not in the other trials (OR, 0.96).

Dr. Dagenais concluded that in patients without known heart failure or LVSD, ACE-inhibitors demonstrated consistent and clear benefits for various outcomes. In the 12,000 patients with heart failure or LVSD, there was also consistency, with a four-fold risk reduction throughout a broad range of outcomes except for stroke.

He also suggested that in patients with coronary artery disease, it was unlikely that the benefits of ACE-inhibitors differed among patients with varying levels of risks or according to ancillary treatments. He recommended that ACE-inhibitors be considered in patients with any evidence of vascular atherosclerotic disease.

A discussant at the meeting, Nicholas Danchin, MD, of Canada, said, “The difference in PEACE results from those in HOPE and EUROPA is possibly accounted for by lower risk in the PEACE population but [is] more likely due to insufficient doses of tran-dolapril.”