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.

Abstract

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.

• Authors: D Waters, L Higginson, P Gladstone, B Kimball, M Le May, S J Boccuzzi, J Lespérance
• Journal: Circulation (Circulation) Vol. 89 Issue 3 Pg. 959-68 (Mar 1994) ISSN: 0009-7322 [Print] United States
• PMID: 8124836 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• Cholesterol
• Lovastatin

Topics

• Canada (epidemiology)
• Cholesterol (blood)
• Coronary Angiography
• Coronary Artery Disease (diagnostic imaging, drug therapy, epidemiology)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids (blood)
• Lovastatin (therapeutic use)
• Male
• Middle Aged
• Multivariate Analysis
• Time Factors