Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).
BACKGROUND
Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients.


RESULTS
A total of 732 patients >/=55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E (RRR-alpha-tocopheryl acetate) 400 IU/d or their matching placebos. Average follow-up was 4.5 years. Atherosclerosis progression was evaluated by B-mode carotid ultrasound. The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo.


CONCLUSIONS
Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.
Lonn
E
E
Departments of Medicine, McMaster University, Hamilton, Ontario, Canada. hope@ccc.mcmaster.ca
Yusuf
S
S
Dzavik
V
V
Doris
C
C
Yi
Q
Q
Smith
S
S
Moore-Cox
A
A
Bosch
J
J
Riley
W
W
Teo
K
K
D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011188:Potassium / Q000097:blood; D011446:Prospective Studies; D017257:Ramipril / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014810:Vitamin E / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014810:Vitamin E; D003404:Creatinine; D017257:Ramipril; D011188:Potassium