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Circulation. 2001;103:919-925

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(Circulation. 2001;103:919.)
© 2001 American Heart Association, Inc.


Clinical Investigation and Reports

Effects of Ramipril and Vitamin E on Atherosclerosis

The Study to Evaluate Carotid Ultrasound Changes in Patients Treated With Ramipril and Vitamin E (SECURE)

Eva M. Lonn, MD, MSc; Salim Yusuf, MBBS, DPhil; Vladimir Dzavik, MD; C. Ian Doris, MBChB; Qilong Yi, PhD; Sandra Smith, RDMS; Anne Moore-Cox, RDMS; Jackie Bosch, MSc; Ward A. Riley, PhD; Koon K. Teo, MB, PhD; for the SECURE Investigators

From the Departments of Medicine (E.M.L., S.Y., Q.Y., S.S., A.M.-C., J.B., K.K.T.) and Radiology (C.I.D.), McMaster University, Hamilton, Ontario, Canada; The University of Alberta Hospitals, Edmonton, Alberta, Canada (V.D., K.K.T.); the Canadian Cardiovascular Collaboration (E.M.L., S.Y., V.D., C.I.D., Q.Y., S.S., A.M.-C., J.B., K.K.T.); and the Bowman Gray School of Medicine, Department of Neurology, Winston-Salem, NC (W.A.R.).

Correspondence to Eva Lonn, MD, Hamilton Health Sciences Corporation, General Site, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2. E-mail hope{at}ccc.mcmaster.ca

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.

Methods and 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.


Key Words: atherosclerosis • angiotensin • carotid arteries • ultrasonics




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