This study examined the effects of long term cholesterol lowering therapy with simvastatin on progression and regression of coronary atherosclerosis, as determined by quantitative angiographic end points, in subgroups of patients with known coronary risk factors. In this randomized, placebo controlled clinical trial, the effect of simvastatin on coronary atherosclerosis was compared with that of placebo in 394 patients who had paired coronary angiograms taken an average of four years apart. The effects of treatment on the following prespecified subgroups were examined: sex, age (less than 65 years versus at least 65 years), smoking status (current or previous/never), history of diabetes mellitus or hypertension, and severity of coronary artery lesions (diameter at least 50% versus less than 50%). There were significantly smaller decreases in the average minimum diameters, between closeout and baseline angiograms, in all simvastatin-treated subgroups, compared with placebo. Trends toward or significantly smaller decreases in the average of the mean diameters, and similar smaller increases in percentage diameter stenosis were also seen in all subgroups. The slowing of angiographically demonstrable coronary atherosclerotic narrowing supports the contention that this treatment effect is causally related to the reduction of coronary events repeatedly seen in large outcome clinical trials of lipid lowering therapy. Also, this treatment effect occurs in the presence or absence of the traditional coronary risk factors.