Studies of lipid-lowering therapy are usually conducted in patients with severely elevated cholesterol levels. However, most individuals who develop clinically significant coronary artery disease (CAD) have total cholesterol levels <240 mg/dL and low-density lipoprotein (LDL) cholesterol levels similar to individuals who do not develop significant CAD. The Lipoprotein and Coronary Atherosclerosis Study (LCAS) was conducted to determine whether lipid-lowering therapy with fluvastatin would reduce the progression or induce the regression of coronary atherosclerotic lesions and/or reduce new lesion formation in patients with CAD and mildly to moderately elevated LDL cholesterol. The LCAS was the first angiographically monitored trial of this 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All 429 men and women (mean age, 58.8 years) had angiographic evidence of CAD and LDL cholesterol levels of 115–190 mg/dL (mean 145.6 mg/dL). Patients were randomized to fluvastatin 20 mg twice daily or placebo. Patients whose prerandomization LDL cholesterol was ≥160 mg/dL also received open-label cholestyramine. Lipid-lowering therapy with fluvastatin significantly slowed CAD progression. After 2.5 years, the mean LDL cholesterol decreased by 23.9% in all fluvastatin-treated patients (± cholestyramine) and by 22.5% in patients treated with fluvastatin monotherapy. There was significantly less lesion progression in fluvastatin versus placebo-treated patients (p <0.01). There also were fewer clinical events in fluvastatin-treated patients. Findings suggest that fluvastatin may improve arterial and arteriolar function within a few weeks of beginning therapy.