PRAVASTATIN LIMITATION OF ATHEROSCLEROSIS IN THE CORONARY-ARTERIES (PLAC-I) - REDUCTION IN ATHEROSCLEROSIS PROGRESSION AND CLINICAL EVENTS

Objectives. This study was designed to evaluate the effect of pravastatin on progression of coronary atherosclerosis and ischemic events in patients with coronary artery disease and mild to moderate hyperlipidemia. Background. Pew clinical trial data support the use of Lipid-lowering therapy in patients with coronary artery disease and mild to moderate elevations in cholesterol levels. Methods. Pour hundred eight patients (mean age 57 years) with coronary artery disease and low density lipoprotein (LDL) cholesterol greater than or equal to 130 mg/dl (3.36 mmol/liter) but <190 mg/dl ([4.91 mmol/liter]) despite diet were randomized in a 3-year study to receive pravastatin or placebo. Atherosclerosis progression was evaluated by quantitative coronary arteriography. Results. Baseline mean LDL cholesterol was 164 mg/dl (4.24 mmol/liter). Pravastatin decreased total and LDL cholesterol and triglyceride levels by 19%, 28% and 8%, respectively, and increased high density lipoprotein cholesterol by 7% (p less than or equal to 0.001 vs. placebo for all lipid variables). Progression of atherosclerosis was reduced by 40% for minimal vessel diameter (p = 0.01), particularly in lesions <50% stenosis at baseline, There was a consistent although not statistically significant effect on mean diameter and percent diameter stenosis. There were also fewer new lesions in those assigned pravastatin (p less than or equal to 0.03). Myocardial infarction was reduced during active treatment (8 in the pravastatin group, 17 in the placebo group; log-rank test, p less than or equal to 0.05; 60% risk reduction), with the benefit beginning to emerge after 1 year. Conclusions. In patients with coronary artery disease and mild to moderate cholesterol elevations, pravastatin reduces progression of coronary atherosclerosis and myocardial infarction. The time course of event reduction increases the potential for a relatively rapid decrease in the clinical manifestations of coronary artery disease with lipid lowering.