A Double-Blind, Placebo-Controlled Angiographic Study to Evaluate the Effect of Lovastatin on the Progression Rate of Atherosclerosis in the Coronary Arteries of Patients With Coronary Heart Disease

Two conceptual advances occurring in the 1980's made it possible to test the hypothesis that significant alterations in serum lipoproteins can substantially reduce atherosclerosis progression or even induce regression. The first advance was in the development of arteriograms used in characterizing atherosclerosis, greatly reducing the number of patients required for the evaluation of an intervention designed to prevent coronary atherosclerosis progression. The second advance was the development of lovastatin that provides a lipid-lowering alternative much easier to tolerate than the niacin/colestipol combination previously used, and has been shown to be comparably effective for LDL reduction in patients with a family history of high cholesterol.

A total of 270 high-risk coronary artery disease patients, not eligible for coronary artery bypass surgery, were recruited for the study. All patients received angiograms and were randomly assigned to either the lovastatin or placebo groups stratified by three baseline factors: sex, smoking status, and plasma cholesterol levels.

Patients initially received lovastatin 40mg twice a day or a matching placebo. Those patients receiving lovastatin whose total plasma cholesterol level was less than 110mg/dL at one visit or 120 mg/dL on two successive visits had their dosage halved, and were maintained on the optimal dosage for the remainder of the study. Coronary angiography was performed prior to screening and at month 24 (visit 18). Angiographic assessment of both femoral arteries was also performed at baseline and at month 24. Noninvasive ultrasound imaging of the carotid arteries (including carotid intima-media thickness) was performed every 6 months. Patients reported to the clinic monthly for 12 months, and at two-month intervals thereafter. Plasma lipids, routine laboratory safety and physical examinations were also performed.