Am J Cardiol. 1998 Nov 26;82(10B):53T-56T. Pedersen TR. Department of Cardiology, Aker Hospital, Oslo, Norway. Although hyperlipidemia is a known risk factor for coronary artery disease, lipid-lowering agents were not used widely until recently because evidence was lacking that they could prolong life. In 1987, a large clinical trial, the Scandinavian Simvastatin Survival Study (4S), was designed to test whether such therapy could decrease all-cause mortality in patients with documented coronary artery disease. The prospective, randomized, multicenter trial included 4,444 patients who had had angina pectoris or myocardial infarction (MI), serum total cholesterol of 213-310 mg/dL, and serum triglycerides < or =221 mg/dL. Patients received either simvastatin 20-40 mg/day or placebo and were followed for a median of 5.4 years. Therapy decreased total cholesterol an average of 25%; low-density lipoprotein (LDL) cholesterol, 35%; and triglyceride levels, 10%. Therapy increased high-density lipoprotein (HDL) cholesterol levels 8%. Although noncardiac death rates were similar among the groups, the relative risk of mortality (from any cause) was decreased 30%, and the relative risk of coronary mortality was decreased 42% in the simvastatin arm. The mortality risk reductions were profound in patients > or =60 years of age. Treatment also significantly decreased the relative risk of coronary events and the need for bypass surgery or coronary angioplasty. Patients with diabetes also benefited significantly from simvastatin therapy. The reductions in relative risk of major coronary events were achieved irrespective of such baseline risk factors as hypertension and smoking and such medication factors as aspirin, beta-blocker, and calcium-antagonist use. Simvastatin therapy has been shown to be cost-effective, decreasing per-patient hospitalization costs by 31% or