Circulation. 2001 Feb 20;103(7):919-25. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Lonn E， Yusuf S， Dzavik V， Doris C， Yi Q， Smith S， Moore-Cox A， Bosch J， Riley W， Teo K; SECURE Investigators. Departments of Medicine， McMaster University， Hamilton， Ontario， Canada. hope@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.