RESULTS OF THE PRIMARY OUTCOME MEASURE AND CLINICAL EVENTS FROM THE ASYMPTOMATIC CAROTID-ARTERY PROGRESSION STUDY

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven to be more effective in reducing levels of low density lipoprotein (LDL) cholesterol and to be better tolerated than other lipid-lowering compounds. Most of the trials evaluating the effects of these new agents on progression of atherosclerosis have not included individuals asymptomatic for cardiovascular disease and who have LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program for initialing treatment, The Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis Ias detected by B-mode ultrasonography) in 919 asymptomatic men and women, 40-79 years of age, who had LDL cholesterol levels between the 60th and 90th percentiles. Participants randomized into this double-blind, placebo-controlled, factorially designed study received lovastatin (20-40 mg/day) or lovastatin placebo and warfarin (1 mg/day), or warfarin-placebo over a 3-year period. The progression of the mean maximum intimal-medial thickness (IMT) over 12 walls of both carotid arteries represented the primary outcome. Lovastatin treatment was associated with a reduction in progression of mean maximum IMT (p < 0.001). Levels of LDL cholesterol were reduced by 28% (43.5 mg/dl [11.25 mmol/liter]) in the lovastatin group within 6 months (p < 0.0001) and remained stable throughout the follow-up period, whereas these levels remained essentially unchanged in the lovastatin-placebo group. The difference in incidence of major cardiovascular events fbr patients in the lovastatin group compared with patients in the lovastatin-placebo group was significant: 5 versus 14, respectively (p < 0.05). A difference in all-cause mortality between these 2 groups also was noted: 1 versus 8, respectively (p < 0.05). Univariate and multivariate regression analyses suggested greater primary outcome benefit in patients who were hypertensive, followed a National Cholesterol Education Program step 1 diet, or were women using hormone replacement therapy. in ACAPS, men and women with moderately elevated levels of LDL cholesterol experienced reversal df early-stage carotid IMT progression while they received lovastatin. Reductions in the incidence of major cardiovascular events and all-cause mortality associated with HMG-CoA reductase inhibitor therapy have subsequently been confirmed in a large, secondary prevention trial.