Effects of Ramipril and Vitamin E on Atherosclerosis

TLDR

Activation of the renin‑angiotensin‑aldosterone system and oxidative LDL modification contribute to atherosclerosis. In a prospective, double‑blind, 3×2 factorial trial of 732 high‑risk patients aged ≥55, participants were randomized to ramipril 2.5 or 10 mg/d, vitamin E 400 IU/d, or placebos, followed for an average of 4.5 years, with atherosclerosis progression assessed by B‑mode carotid ultrasound. Ramipril reduced carotid intima‑media thickness progression (0.0217 mm/yr placebo vs 0.0180 mm/yr 2.5 mg/d and 0.0137 mm/yr 10 mg/d, P = 0.033), while vitamin E had no effect, indicating long‑term ramipril benefits atherosclerosis progression and vitamin E is neutral.

Abstract

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.