Effects of Ramipril and Vitamin E on Atherosclerosis

• DOI: 10.1161/01.cir.103.7.919
• Publication Date: 2012-06-12T00:09:32Z
• Authors: Eva M. Lonn; Salim Yusuf; Vladimir Dzavik; C. Ian Doris; Qilong Yi; Sandra Smith; Anne Moore-Cox; Jackie Bosch; Ward A. Riley; Koon K. Teo
• Keywords: Carotid Artery Diseases; Male; Analysis of Variance; Arteriosclerosis; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Middle Aged; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Double-Blind Method; Ramipril; Risk Factors; Creatinine; Disease Progression; Potassium; Humans; Patient Compliance; Female; Prospective Studies; Aged; Follow-Up Studies

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, 3×2 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-α-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.