Design and recruitment in the United States of a multicenter quantitative angiographic trial of pravastatin to limit atherosclerosis in the coronary arteries (PLAC I)

The present study was designed to test the effect of pravastatin, a new, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the progression of coronary artery disease in patients with moderate hypercholesterolemia. Angiographic entry criteria included the presence of>=1 stenosis>=50% in a major epicardial coronary artery, and certification of film quality through the core angiography laboratory. Patients qualified for randomization if after diet stabilization their low density lipoprotein cholesterol concentrations were>=130 and <190 mg/dl, and triglycerides were <= 350 mg/dl. Pravastatin (40 mg) or placebo is administered once daily at bedtime. Arteriography will be repeated at the end of 3 years of treatment. The primary end point of the study is the change in absolute mean coronary artery diameter. During a 30-month recruitment period, 44,145 patients were screened, and 408 were randomized. The most frequent reason for excluding patients during the screening and dietary lead-in periods was a low serum cholesterol level. A large proportion of patients with documented coronary artery disease have cholesterol concentrations that are considered to be normal or only modestly increased. Adherence to strict standards of quality control for digital analysis of angiograms ensures that baseline angiograms can be interpreted at the end of 3-year follow-up.