CLINICAL STUDIES
Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease
Stephen MacMahon, PhD, MPH, FACC*,
Norman Sharpe, MD, FRACP, FACC ,
Greg Gamble, MSc,
Alison Clague, RN ,
Cliona Ni Mhurchu, PhD,
Taane Clark, MSc,
Hamish Hart, MB, ChB, FRACP ,
John Scott, MD, FRACP||,
Harvey White, DSc, FRACP, FACC¶ PART-2 Collaborative Research Group
* Institute for International Health and Department of Medicine, University of Sydney, Sydney, Australia
Department of Medicine, University of Auckland, Auckland, New Zealand
Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand
Department of Medicine, North Shore Hospital, Auckland, New Zealand
|| Department of Medicine, University of Auckland, Auckland, New Zealand
¶ Coronary Care and Cardiovascular Research Units, Greenlane Hospital, Auckland, New Zealand
Manuscript received October 20, 1999;
revised manuscript received January 26, 2000,
accepted March 29, 2000.
Reprint requests and correspondence: Dr. Stephen MacMahon, Institute for International Health, The University of Sydney, PO Box 1225, Crows Nest, Sydney NSW 1585, Australia
OBJECTIVES
The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease.
BACKGROUND
Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis.
METHODS
Six hundred seventeen patients were randomized in equal proportions to ramipril (5–10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography.
RESULTS
Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p < 0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04).
CONCLUSIONS
The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | BP | = blood pressure | | CHF | = congestive heart failure | | HOPE | = Heart Outcomes Prevention Evaluation | | LV | = left ventricle (left ventricular) | | MI | = myocardial infarction | | TIA | = transient ischemic attack |
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