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Circulation, Vol 89, 959-968, Copyright © 1994 by American Heart Association
D Waters, L Higginson, P Gladstone, B Kimball, M Le May, SJ Boccuzzi and J Lesperance
BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are
widely prescribed for hyperlipidemia, yet their effect on the evolution of
coronary atherosclerosis has not been defined. METHODS AND RESULTS: To
address this issue, 331 patients with diffuse but not necessarily severe
coronary atherosclerosis documented on a recent arteriogram and with
fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a
randomized, double-blind, placebo-controlled trial. All patients received
intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d
and was titrated to 40 and 80 mg during the first 16 weeks to attain a
fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The
mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after
2 years. In 299 patients (90%), 3858 coronary segments containing 2309
stenoses were measured blindly on pairs of films with an automated
computerized quantitative system. Total and LDL cholesterol decreased by 21
+/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but
changed by < 2% in placebo patients. The primary end point, coronary
change score, defined as the per-patient mean of the minimum lumen diameter
changes (follow-up minus baseline angiogram) for all lesions measured,
excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the
placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01).
Progression (a worsening in minimum diameter of one or more stenoses by
> or = 0.4 mm) with no regression at other sites occurred in 48 of 146
lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New
coronary lesions developed in 23 lovastatin and 49 placebo patients (P =
.001). The beneficial effect of treatment was most pronounced in the more
numerous, milder lesions and in patients whose baseline total or LDL
cholesterol levels were above the group median. CONCLUSIONS: Lovastatin
slows the progression of coronary atherosclerosis and inhibits the
development of new coronary lesions.
ARTICLES
Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial
Division of Cardiology, Hartford Hospital, Conn 06115.
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