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 inhibito rs have proven to be more effective in reducing levels of low density lipoprotein (LDL) cholesterol and to be better tolerated than other li pid-lowering compounds. Most of the trials evaluating the effects of t hese new agents on progression of atherosclerosis have not included in dividuals asymptomatic for cardiovascular disease and who have LDL cho lesterol levels at or below the limits established by the National Cho lesterol 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 atheroscle rosis 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 doubl e-blind, placebo-controlled, factorially designed study received lovas tatin (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 ma ximum intimal-medial thickness (IMT) over 12 walls of both carotid art eries represented the primary outcome. Lovastatin treatment was associ ated 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 remai ned stable throughout the follow-up period, whereas these levels remai ned essentially unchanged in the lovastatin-placebo group. The differe nce in incidence of major cardiovascular events fbr patients in the lo vastatin 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 anal yses suggested greater primary outcome benefit in patients who were hy pertensive, followed a National Cholesterol Education Program step 1 d iet, or were women using hormone replacement therapy. in ACAPS, men an d women with moderately elevated levels of LDL cholesterol experienced reversal df early-stage carotid IMT progression while they received l ovastatin. Reductions in the incidence of major cardiovascular events and all-cause mortality associated with HMG-CoA reductase inhibitor th erapy have subsequently been confirmed in a large, secondary preventio n trial.