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 initiating treatment. The Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis (as 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 for patients in the lovastatin-placebo group was significant: 5 versus 14, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Probstfield
J L
JL
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Margitic
S E
SE
Byington
R P
RP
Espeland
M A
MA
Furberg
C D
CD
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D016896:Treatment Outcome; D014463:Ultrasonography; D014859:Warfarin / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D000925:Anticoagulants; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014859:Warfarin; D008148:Lovastatin