[en] Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antilipemic Agents/administration & dosage/pharmacology ; Coronary Artery Disease/drug therapy ; Diabetes Complications ; Female ; Humans ; Male ; Middle Aged ; Placebos ; Randomized Controlled Trials as Topic ; Sex Factors ; Simvastatin/administration & dosage/pharmacology ; Stroke/prevention & control ; Survival Analysis ; Treatment Outcome
[en] 20,536 adults (15,454 men and 5,082 women, aged 40-80 years) with coronary heart disease, other occlusive arterial disease or diabetes mellitus were randomly allocated to receive 40 mg simvastatin daily or matching placebo. In addition to being randomized to compare simvastatin vs placebo, all patients were also randomized to compare antioxidant vitamin supplementation (vitamin E 600 mg/day, vitamin C 250 mg/day and betacarotene 20 mg/day) vs placebo in a "2 x 2 factorial" design. Duration of the study was 5 years. All-cause mortality was significantly reduced among patients allocated to simvastatin (-12.3%) due to a highly significant (-18%) reduction in the coronary death rate, a marginally significant reduction in other vascular deaths and a non-significant reduction in non-vascular deaths. There were highly significant reductions (of about one-quarter) in the first event rate for non-fatal myocardial infarction and coronary death (combined), for non-fatal and fatal stroke and for coronary or non-coronary revascularization. The beneficial effect of simvastatin was seen in all sub-categories which were studied and, particularly: women vs men; patients aged > 70 years vs those aged < 70 years; patients with LDL cholesterol < vs > 116 mg/dl, or total cholesterol < vs > 193 mg/dl. The treatment was well tolerated and the annual risk of myopathy was 0.01%. All comparisons between antioxidant vitamin supplementation and placebo failed to reveal any difference in favour or against the supplementation which was otherwise well tolerated. These important results and their implications will be briefly discussed.