PRAVASTATIN, LIPIDS, AND ATHEROSCLEROSIS IN THE CAROTID ARTERIES (PLAC-II)

The Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries t rial (PLAC-II) was initiated in 1987 and was the first double-blind, r andomized clinical trial with progression of early extracranial caroti d atherosclerosis as an outcome variable. We randomized 151 coronary p atients to placebo or pravastatin and treated them for 3 years. B-mode ultrasound quantification of carotid artery intimal-medial thickness (IMT) was obtained at baseline and sequentially during this period. Th e primary outcome was the change in the mean of the maximum IMT measur ements over time. Effects on individual carotid artery segments (commo n, bifurcation, internal carotid artery) and on clinical events were a lso investigated. During follow-vp, plasma concentrations of total cho lesterol were lower in pravastatin-treated patients compared with thos e of placebo-treated patients (4.81 vs 6.08 mmol/liter [186 vs 235 mg/ dl]) as were concentrations of low density lipoprotein (LDL) cholester ol (3.10 vs 4.29 mmol/liter [120 vs 167 mg/dl]). Plasma concentrations of high density lipoprotein(2) (HDL(2)) cholesterol were higher in pr avastatin-treated patients than in placebo-treated patients (0.16 vs 0 .14 mmol/liter [6.1 vs 5.5 mg/dl]). Active treatment resulted in a non significant 12% reduction in progression of the mean-maximum IMT (from 0.068 mm/yr placebo to 0.059 mm/yr pravastatin) and a statistically s ignificant 35% reduction in IMT progression in the common carotid (p = 0.03). Active treatment was also associated with a 60% reduction of n onfatal myocardial infarction plus death caused by coronary artery dis ease (p = 0.09), a 61% reduction of any fatal event plus any nonfatal myocardial infarction (p = 0.04), and an 80% reduction of fatal plus a ny nonfatal myocardial infarction (p = 0.03).