Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.
OBJECTIVE
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.
Institute for International Health and Department of Medicine, University of Sydney, NSW, Australia.
S
S
MacMahon
N
N
Sharpe
G
G
Gamble
A
A
Clague
C N
CN
Mhurchu
T
T
Clark
H
H
Hart
J
J
Scott
H
H
White
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000150:complications*; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology; D003327:Coronary Disease / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril