Regression of coronary artery disease as a result of intensive lipidlowering therapy in men with high levels of apolipoprotein B

Author

Brown G, Albers JJ, Fisher LD, et al. Reference

N Engl J Med 1990; 323: 1289-1298 Abstract

BACKGROUND AND METHODS: The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2.5-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). RESULTS: The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent). In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent. By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; p less than 0.005). Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions. Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77). CONCLUSIONS: In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events.

Summary

This study describes the change of angiographical lesion severity during lipid-lowering treatment concordant with clinical benefit.

Citation Count 1347

Related References

1. Jukema JW, Bruschke AV van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation 1995; 91: 2528-2540.

2. Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic Changes with Lovastatin Therapy. The Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 1993; 119: 969-976.

3. Pitt B, Mancini GB, Ellis SG, Rosman HS, Park J-S, McGovern ME. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol 1995; 26: 1133-1139.

4. MAAS Investigators. Effect of Simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet 1994; 344: 633-638.

5. Waters D, Higginson L, Gladstone P, et al. 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. Circulation 1994; 89: 959-968.

Key message

Our results show that quantitative arteriography is an effective method of assessing interventions against the atherosclerotic process. Although it answers different questions from those answered by clinical trials, arteriography permits a direct assessment of the vascular processes underlying clinical disorders, and it is currently the only reliable way to study the regression of lesions.

Why it's important

This and other studies demonstrated less progression or greater propensity for regression in the treatment group and demonstrated the value of luminal dimensions in the assessment of disease severity as a clinical endpoint.

Strengths

Applies coronary angiography to the quantitative assessment of atherosclerosis progression and regression in clinical research.

Weaknesses

The authors describe that other pathological processes including arterial remodelling, vasomotor tone, and endothelial function initiate changes of arterial architecture independent of changes in luminal dimension.

Relevance

These studies demonstrate the dynamic nature of coronary artery disease (CAD) and the value of luminal dimensions in the assessment of disease severity.

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