Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Lipid-lowering drug therapy reversed the progression of coronary disease and reduced cardiovascular events in men with high lipid levels

ACP J Club. 1991 Mar-Apr;114:40. doi:10.7326/ACPJC-1991-114-2-040


Source Citation

Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-98.


Abstract

Objective

To compare 2 intensive strategies for lowering lipid levels (niacin-colestipol [N-C] and lovastatin-colestipol [L-C]) with a more conventional approach (control group) in men with established coronary atherosclerosis.

Design

Randomized, double-blind, placebo-controlled trial of 2.5-years' duration.

Setting

Northwest Lipid Research Clinic, a referral center in Seattle.

Patients

Patients were eligible if they had elevated apolipoprotein B levels (> 125 mg/dL), a family history of coronary artery disease, and coronary artery stenosis on angiography. Patients were excluded if they had other causes of lipid or cardiovascular disorders or had had revascularization. Of 232 eligible men, 146 (63%) agreed, and 120 (82% of those enrolled) completed the study.

Intervention

All patients received diet counseling. Patients in the N-C group (n = 36) started niacin, 125 mg twice daily, increased to as much as 6 g/d, plus colestipol, started at 5 g 3 times daily, increased to 30 g/d. The L-C group (n = 38) received colestipol (same dosage), plus lovastatin, 20 to 40 mg twice daily. The control group (n = 46) received placebos for colestipol and lovastatin, or colestipol if their low-density lipoprotein (LDL) cholesterol level exceeded the 90th percentile for age (43% of the group).

Main outcome measure

Change in LDL-cholesterol levels, percentage change in coronary stenosis, and occurrence of cardiovascular events.

Main results

The LDL cholesterol levels fell 7% in the control group, 46% in the L-C group, and 32% in the N-C group. High-density lipoprotein (HDL) cholesterol levels rose 5% in the control group, 15% in the L-C group, and 43% in the N-C group. Mean coronary stenosis was 34% at baseline; this increased 2.1 percentage points in the control group, and decreased 0.7 point in the L-C group, and 0.9 point in the N-C group (P for trend < 0.003). Cardiovascular events occurred in 3 patients (4%) receiving N-C compared with 10 patients (19%) receiving placebo. (P = 0.01). {This absolute risk reduction of 15% means that 7 patients would need to be treated with N-C for a mean of 2.5 years (compared with placebo) to prevent 1 additional patient from having a cardiovascular event, 95% CI 4 to 37; the relative risk reduction was 78%, CI 18% to 95%.}* Patients receiving L-C also had fewer cardiovascular events (7%), but this did not differ from the placebo group { P = 0.06}.*

Conclusions

In men with high levels of apolipoprotein B and established coronary artery stenosis, intensive lipid-lowering drug therapy reversed the progression of coronary lesions and reduced the incidence of cardiovascular events.

Sources of funding: National Institutes of Health and John L. Locke, Jr., Charitable Trust.

Address for article reprint: Dr. G. Brown, Cardiology Division, RG-22, University of Washington, Seattle, WA 98195, USA.

*Numbers calculated from data in article.


Commentary

This extremely important study indicates that large reductions in LDL-cholesterol (LDL-C, apolipoprotein B) combined with large increases in HDL-cholesterol (HDL-C) lead to regression or decreased progression of coronary stenosis. These results are more impressive because 43% of the control group participants received colestipol for very high levels of LDL-C, reducing the chance of showing a benefit in the other groups. Regression of atherosclerotic stenosis through aggressive antilipid therapy has been confirmed in 2 other major studies: the Cholesterol-Lowering Atherosclerosis Study (CLAS) (1) and the Program on the Surgical Control of the Hyperlipidemias (POSCH) study (2). Subsequent large clinical trials with Statis monotherapy have shown moderate clinical benefit (3, 4).

The study does not indicate that niacin-colestipol (which raised HDL-C more) is superior to lovastatin-colestipol (which lowered LDL-C more). The treated LDL-C/HDL-C ratios were 2.3 in the N-C group and 2.6 in the L-C group. These ratios are similar to that in the CLAS study (1.7), using niacin and colestipol, and to the 2.5 ratio, achieved by partial ileal bypass in the POSCH study. This finding suggests that, whether the HDL or LDL cholesterol or both are manipulated, a goal of 1.7 to 2.5 may be a useful guideline for secondary preventive treatment.

These results have been shown only for middle-aged men with proven coronary heart disease and elevated LDL cholesterol levels. Further studies are needed for other groups, particularly women and older men.

Donald A. Smith, MD, MPH
Mount Sinai Medical CenterNew York, New York, USA


References

1. Blankenhorn DH, Nessiom SA, Johnson RL, et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987;257:3233-40.

2. Buchwald H, Varco RL, Matts JP, et al., and the POSCH Group. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med. 1990;323:946-55.

3. Scandinavian Simvastatin Survival Group Study. Randomised trial of cholesteral lowering in 444 patients with coronary heart disease; the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344:1383-9.

4. Shepherd J, Cobbe SM, Ford I, et al. for the west of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-7.