Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study.

In the National Heart, Lung and Blood Institute Type II Coronary Intervention Study, patients with Type II hyperlipoproteinemia and coronary artery disease (CAD) were placed on a low-fat, low-cholesterol diet and then were randomly allocated to receive either 6 g cholestyramine four times daily or placebo. This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography. Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group. Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant. However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05). Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant. Thus, although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.

[1]  N. Ernst,et al.  Nutrition in health and disease, Vol. 1. Nutrition, lipids, and coronary heart disease. A global view. , 1979 .

[2]  S. Kelsey,et al.  Reliability of assessing change with sequential coronary angiography. , 1982, American heart journal.

[3]  J. Stamler.  The coronary drug project. Findings leading to further modifications of its protocol with respect to dextrothyroxine. The coronary drug project research group. , 1972, JAMA.

[4]  R. Levy.  Dietary Prevention of Coronary Artery Disease—A Policy Overview , 1980 .

[5]  S. Kelsey,et al.  The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of NHLBI Type II Coronary Intervention Study. , 1984, Circulation.

[6]  E. Buskirk.  The National Diet-Heart Study Final Report. , 1969, Circulation.

[7]  M. Bond,et al.  A study of atherosclerosis regression in Macaca mulatta. I. Design of experiment and lesion induction. , 1979, Experimental and molecular pathology.

[8]  R. Levy.  Cholesterol, lipoproteins, apoproteins, and heart disease: present status and future prospects. , 1981, Clinical chemistry.

[9]  R. Wissler,et al.  Reversal of advanced atherosclerosis in Rhesus monkeys: Part 1. Light-microscopic studies☆ , 1976 .

[10]  James J Schlesselman.  Case-Control Studies: Design, Conduct, Analysis , 1982 .

[11]  V. McGuire.  The dietary management of hyperlipoproteinemia. , 1977, Advances in experimental medicine and biology.

[12]  N. Ernst,et al.  Dietary management of hyperlipoproteinemia. , 1971, Journal of the American Dietetic Association.

[13]  A. Gotto,et al.  Cholestyramine in type II hyperlipoproteinemia. A double-blind trial. , 1973, Annals of internal medicine.

[14]  W. Kannel,et al.  Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. , 1979, Annals of internal medicine.

[15]  S. Kelsey,et al.  National Heart, Lung, and Blood Institute type II Coronary Intervention Study: design, methods, and baseline characteristics. , 1982, Controlled clinical trials.

[16]  M. Armstrong,et al.  Arterial Fibrous Proteins in Cynomolgus Monkeys after Atherogenic and Regression Diets , 1975, Circulation research.

[17]  D. Grafnetter,et al.  A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. , 1978, British heart journal.

[18]  The Coronary Drug Project. Initial findings leading to modifications of its research protocol. , 1970, JAMA.

[19]  Jeremy N. Morris,et al.  W.H.O. cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. , 1980 .