Secondary prevention of coronary heart disease by antilipidemic therapy beginning at > or =3 months after an acute coronary syndrome is well documented. The impact, however, of immediate initiation of antilipidemic therapy on coronary stenoses and clinical outcome in patients with acute coronary syndrome is unknown. In our study, patients were randomized, on average, 6 days after an acute myocardial infarction and/or percutaneous transluminal coronary angioplasty secondary to unstable angina, to pravastatin (combined, when necessary, with cholestyramine and/or nicotinic acid) to achieve low-density lipoprotein cholesterol levels of < or =130 mg/dl (group A, n = 70). In controls (group B, n = 56), antilipidemic therapy was determined by family physicians. Quantitative coronary angiography was performed at inclusion, and at 6- and 24-month follow-up. The combined clinical end points were total mortality, cardiovascular death, nonfatal myocardial infarction, need for coronary intervention, stroke, and new onset of peripheral vascular disease. Minimal lumen diameter in group A increased by 0.05 +/- 0.20 mm after 6 months and 0.13 +/- 0.29 mm after 24 months, whereas it decreased by 0.08 +/- 0.20 mm and 0.18 +/- 0.27 mm, respectively, in group B (p = 0.004 at 6 months and p <0.001 at 24 months). After 2 years, 29 patients of 56 patients in group B, but only 16 of 70 patients in group A, experienced a clinical end point (p = 0.005; odds ratio 0.28, confidence intervals 0.13 to 0.6). We conclude that pravastatin-based therapy initiated immediately after an acute coronary syndrome is well tolerated and safe, lessens coronary atherosclerosis, and has a pronounced clinical benefit.