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January 20, 1984, Vol 251, No. 3 >
ARTICLE | January 20, 1984

The Lipid Research Clinics Coronary Primary Prevention Trial Results: Title and subTitle BreakI. Reduction in Incidence of Coronary Heart Disease FREE

[+] Author Affiliations

Reprint requests to Lipid Metabolism-Atherogenesis Branch, National Heart, Lung, and Blood Institute, Federal 401, Bethesda, MD 20205 (Basil M. Rifkind, MD).


JAMA. 1984;251(3):351-364. doi:10.1001/jama.1984.03340270029025
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References

The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), a multicenter, randomized, double-blind study, tested the efficacy of cholesterol lowering in reducing risk of coronary heart disease (CHD) in 3,806 asymptomatic middle-aged men with primary hypercholesterolemia (type II hyperlipoproteinemia). The treatment group received the bile acid sequestrant cholestyramine resin and the control group received a placebo for an average of 7.4 years. Both groups followed a moderate cholesterol-lowering diet. The cholestyramine group experienced average plasma total and low-density lipoprotein cholesterol (LDL-C) reductions of 13.4% and 20.3%, respectively, which were 8.5% and 12.6% greater reductions than those obtained in the placebo group. The cholestyramine group experienced a 19% reduction in risk (P<.05) of the primary end point—definite CHD death and/or definite nonfatal myocardial infarction—reflecting a 24% reduction in definite CHD death and a 19% reduction in nonfatal myocardial infarction. The cumulative seven-year incidence of the primary end point was 7% in the cholestyramine group v8.6% in the placebo group. In addition, the incidence rates for new positive exercise tests, angina, and coronary bypass surgery were reduced by 25%, 20%, and 21%, respectively, in the cholestyramine group. The risk of death from all causes was only slightly and not significantly reduced in the cholestyramine group. The magnitude of this decrease (7%) was less than for CHD end points because of a greater number of violent and accidental deaths in the cholestyramine group. The LRC-CPPT findings show that reducing total cholesterol by lowering LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of raised LDL-C levels. This clinical trial provides strong evidence for a causal role for these lipids in the pathogenesis of CHD.

(JAMA 1984;251:351-364)

REFERENCES

1 +
Levy RI: Review:  Declining mortality in coronary heart disease . Arteriosclerosis 1981;; 1:312-325.
2 +
Gordon T, Castelli WP, Hjortland MC, et al:  The prediction of coronary heart disease by high-density and other lipoproteins: An historical perspective , in Rifkind B, Levy R (eds): Hyperlipidemia—Diagnosis and Therapy . New York, Grune & Stratton Inc, 1977;, pp 71-78.
3 +
Stamler J:  Population studies , in Levy RI, Rifkind BM, Dennis BH, et al (eds): Nutrition, Lipids, and Coronary Heart Disease . New York, Raven Press, 1979;, pp 25-88.
4 +
Arteriosclerosis: A Report by the National Heart and Lung Institute Task Force on Arteriosclerosis , Dept of Health, Education, and Welfare publication (NIH) 72-137. Washington, DC, National Institutes of Health, 1971;, vol 1.
5 +
Levy RI, Fredrickson DS, Stone NJ, et al:  Cholestyramine in type II hyperlipoproteinemia: A double-blind trial . Ann Intern Med 1973;; 79:51-58.
6 +
 The Lipid Research Clinics Program: The Coronary Primary Prevention Trial: Design and implementation . J Chronic Dis 1979;;32:609-631.
7 +
Protocol for the Lipid Research Clinics Type II Coronary Primary Prevention Trial . Chapel Hill, NC, University of North Carolina Department of Biostatistics, 1980;.
8 +
 The Lipid Research Clinics Program: Participant recruitment to the Coronary Primary Prevention Trial . J Chronic Dis 1983;;36:451-465.
9 +
 The Lipid Research Clinics Program: Recruitment for clinical trials: The Lipid Research Clinics Coronary Primary Prevention Trial experience . Circulation 1982;;66( (suppl 4) ):1-78.
10 +
 The Lipid Research Clinics Program: Preentry characteristics of participants in the Lipid Research Clinics Coronary Primary Prevention Trial . J Chronic Dis 1983;;36:467-479.
11 +
Dennis B, Ernst N, Hjortland M, et al:  The NHLBI nutrition data system . J Am Diet Assoc 1980;;77:641-647.
12 +
Kalbfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data . New York, John Wiley & Sons, 1980;.
13 +
O'Brien PC, Fleming TR:  A multiple testing procedure for clinical trials . Biometrics 1979;;35:549-556.
14 +
Majundar H, Sen PK:  Nonparametric testing for simple linear regression under progressive censoring with staggering entry and random withdrawal . Communication in Statistics— Theory and Methods . 1978;;A7:349-371.
15 +
Breslow N, Haug C:  Sequential comparison of exponential survival curves . J Am Stat Assoc 1972;;67:691-697.
16 +
Tsiatis AA:  The asymptomatic joint distributions of efficient scores test for the proportional hazards model over time . Biometrika 1981;;68:311-315.
17 +
 Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial Results: II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering . JAMA 1984;;251:365-374.
18 +
 Committee of Principal Investigators, W.H.O. Clofibrate Trial: A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate, report . Br Heart J 1978;; 40:1069-1118.
19 +
H-ICDA: Hospital Adaptation of ICDA , ed 2, eighth revision. Ann Arbor, Mich, Commission on Professional and Hospital Activities, 1973;, vol 1.
20 +
Cornfield J, Mitchell S:  Selected risk factors in coronary disease: Possible intervention effects . Arch Environ Health 1969;;19:382-391.
21 +
Davis CE, Havlik R:  Clinical trials of lipid lowering and coronary artery disease prevention , in Rifkind BM, Levy RI (eds): Hyperlipidemia—Diagnosis and Therapy . New York, Grune & Stratton Inc, 1977;, pp 79-92.
22 +
Rinzler SH:  Primary prevention of coronary heart disease by diet . Bull NY Acad Med 1968;;44:936-949.
23 +
Dayton S, Pearce ML, Hashimoto S, et al:  A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis . Circulation 1969;;39-40(suppl 2):1-63.
24 +
Turpeinen O, Karvonen MJ, Pekkarinen M, et al:  Dietary prevention of coronary heart disease: The Finnish Mental Hospital Study . Int J Epidemiol 1979;;8:99-118.
25 +
Hjermann I, Velve Byre K, Holme I, et al:  Effect of diet and smoking intervention on the incidence of coronary heart disease: Report from the Oslo Study Group of a randomized trial in healthy men . Lancet 1981;;2:1303-1310.
26 +
 Multiple Risk Factor Intervention Trial Research Group: Multiple Risk Factor Intervention Trial: Risk factor changes and mortality results . JAMA 1982;;248:1465-1477.
27 +
Committee of Principal Investigators, W.H.O. Clofibrate Trial:  W.H.O. Cooperative Trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: Mortality follow-up report . Lancet 1980;; 2:379-385.
28 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Initial findings leading to modification of its research protocol . JAMA 1970;;214:1303-1313.
29 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Findings leading to discontinuation of the 2.5 mg/day estrogen group . JAMA 1973;;226:652-657.
30 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Findings leading to further modifications of its protocol with respect to dextrothyroxine . JAMA 1972;;220:996-1008.
31 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Clofibrate and niacin in coronary heart disease . JAMA 1975;; 231:360-381.
32 +
Group of Physicians of the Newcastle Upon Tyne Region:  Trial of clofibrate in the treatment of ischaemic heart disease: Five-year study . Br Med J 1971;;4:767-775
33 +
Research Committee of the Scottish Society of Physicians:  Ischaemic heart disease: A secondary prevention trial using clofibrate . Br Med J 1971;;4:775-784.
34 +
Friedewald WT, Halperin M:  Clofibrate in ischemic heart disease . Ann Intern Med 1972;; 76:821-823.
35 +
Asano T, Pollard M, Madsen DC:  Effects of cholestyramine on 1,2-dimethylhydrazine-induced enteric carcinoma in germfree rats . Proc Soc Exp Biol Med 1975;;150:780-785.
36 +
Oliver MF:  Serum cholesterol: The knave of hearts and the joker . Lancet 1981;;2:1090-1095.
37 +
Kannel WB, Castelli WP, Gordon T, et al:  Serum cholesterol, lipoproteins and the risk of coronary heart disease: The Framingham Study . Ann Intern Med 1971;;74:1-12.
38 +
Goldstein JL, Kita T, Brown MS:  Defective lipoprotein receptors and atherosclerosis: Lessons from an animal counterpart of familial hypercholesterolemia . N Engl J Med 1983;; 309:288-296.
39 +
Blackburn H, Keys A, Simonson E, et al:  The electrocardiogram in population study . Circulation 1960;;21:1160-1175.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Levy RI: Review:  Declining mortality in coronary heart disease . Arteriosclerosis 1981;; 1:312-325.
2 +
Gordon T, Castelli WP, Hjortland MC, et al:  The prediction of coronary heart disease by high-density and other lipoproteins: An historical perspective , in Rifkind B, Levy R (eds): Hyperlipidemia—Diagnosis and Therapy . New York, Grune & Stratton Inc, 1977;, pp 71-78.
3 +
Stamler J:  Population studies , in Levy RI, Rifkind BM, Dennis BH, et al (eds): Nutrition, Lipids, and Coronary Heart Disease . New York, Raven Press, 1979;, pp 25-88.
4 +
Arteriosclerosis: A Report by the National Heart and Lung Institute Task Force on Arteriosclerosis , Dept of Health, Education, and Welfare publication (NIH) 72-137. Washington, DC, National Institutes of Health, 1971;, vol 1.
5 +
Levy RI, Fredrickson DS, Stone NJ, et al:  Cholestyramine in type II hyperlipoproteinemia: A double-blind trial . Ann Intern Med 1973;; 79:51-58.
6 +
 The Lipid Research Clinics Program: The Coronary Primary Prevention Trial: Design and implementation . J Chronic Dis 1979;;32:609-631.
7 +
Protocol for the Lipid Research Clinics Type II Coronary Primary Prevention Trial . Chapel Hill, NC, University of North Carolina Department of Biostatistics, 1980;.
8 +
 The Lipid Research Clinics Program: Participant recruitment to the Coronary Primary Prevention Trial . J Chronic Dis 1983;;36:451-465.
9 +
 The Lipid Research Clinics Program: Recruitment for clinical trials: The Lipid Research Clinics Coronary Primary Prevention Trial experience . Circulation 1982;;66( (suppl 4) ):1-78.
10 +
 The Lipid Research Clinics Program: Preentry characteristics of participants in the Lipid Research Clinics Coronary Primary Prevention Trial . J Chronic Dis 1983;;36:467-479.
11 +
Dennis B, Ernst N, Hjortland M, et al:  The NHLBI nutrition data system . J Am Diet Assoc 1980;;77:641-647.
12 +
Kalbfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data . New York, John Wiley & Sons, 1980;.
13 +
O'Brien PC, Fleming TR:  A multiple testing procedure for clinical trials . Biometrics 1979;;35:549-556.
14 +
Majundar H, Sen PK:  Nonparametric testing for simple linear regression under progressive censoring with staggering entry and random withdrawal . Communication in Statistics— Theory and Methods . 1978;;A7:349-371.
15 +
Breslow N, Haug C:  Sequential comparison of exponential survival curves . J Am Stat Assoc 1972;;67:691-697.
16 +
Tsiatis AA:  The asymptomatic joint distributions of efficient scores test for the proportional hazards model over time . Biometrika 1981;;68:311-315.
17 +
 Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial Results: II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering . JAMA 1984;;251:365-374.
18 +
 Committee of Principal Investigators, W.H.O. Clofibrate Trial: A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate, report . Br Heart J 1978;; 40:1069-1118.
19 +
H-ICDA: Hospital Adaptation of ICDA , ed 2, eighth revision. Ann Arbor, Mich, Commission on Professional and Hospital Activities, 1973;, vol 1.
20 +
Cornfield J, Mitchell S:  Selected risk factors in coronary disease: Possible intervention effects . Arch Environ Health 1969;;19:382-391.
21 +
Davis CE, Havlik R:  Clinical trials of lipid lowering and coronary artery disease prevention , in Rifkind BM, Levy RI (eds): Hyperlipidemia—Diagnosis and Therapy . New York, Grune & Stratton Inc, 1977;, pp 79-92.
22 +
Rinzler SH:  Primary prevention of coronary heart disease by diet . Bull NY Acad Med 1968;;44:936-949.
23 +
Dayton S, Pearce ML, Hashimoto S, et al:  A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis . Circulation 1969;;39-40(suppl 2):1-63.
24 +
Turpeinen O, Karvonen MJ, Pekkarinen M, et al:  Dietary prevention of coronary heart disease: The Finnish Mental Hospital Study . Int J Epidemiol 1979;;8:99-118.
25 +
Hjermann I, Velve Byre K, Holme I, et al:  Effect of diet and smoking intervention on the incidence of coronary heart disease: Report from the Oslo Study Group of a randomized trial in healthy men . Lancet 1981;;2:1303-1310.
26 +
 Multiple Risk Factor Intervention Trial Research Group: Multiple Risk Factor Intervention Trial: Risk factor changes and mortality results . JAMA 1982;;248:1465-1477.
27 +
Committee of Principal Investigators, W.H.O. Clofibrate Trial:  W.H.O. Cooperative Trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: Mortality follow-up report . Lancet 1980;; 2:379-385.
28 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Initial findings leading to modification of its research protocol . JAMA 1970;;214:1303-1313.
29 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Findings leading to discontinuation of the 2.5 mg/day estrogen group . JAMA 1973;;226:652-657.
30 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Findings leading to further modifications of its protocol with respect to dextrothyroxine . JAMA 1972;;220:996-1008.
31 +
Coronary Drug Project Research Group:  The Coronary Drug Project: Clofibrate and niacin in coronary heart disease . JAMA 1975;; 231:360-381.
32 +
Group of Physicians of the Newcastle Upon Tyne Region:  Trial of clofibrate in the treatment of ischaemic heart disease: Five-year study . Br Med J 1971;;4:767-775
33 +
Research Committee of the Scottish Society of Physicians:  Ischaemic heart disease: A secondary prevention trial using clofibrate . Br Med J 1971;;4:775-784.
34 +
Friedewald WT, Halperin M:  Clofibrate in ischemic heart disease . Ann Intern Med 1972;; 76:821-823.
35 +
Asano T, Pollard M, Madsen DC:  Effects of cholestyramine on 1,2-dimethylhydrazine-induced enteric carcinoma in germfree rats . Proc Soc Exp Biol Med 1975;;150:780-785.
36 +
Oliver MF:  Serum cholesterol: The knave of hearts and the joker . Lancet 1981;;2:1090-1095.
37 +
Kannel WB, Castelli WP, Gordon T, et al:  Serum cholesterol, lipoproteins and the risk of coronary heart disease: The Framingham Study . Ann Intern Med 1971;;74:1-12.
38 +
Goldstein JL, Kita T, Brown MS:  Defective lipoprotein receptors and atherosclerosis: Lessons from an animal counterpart of familial hypercholesterolemia . N Engl J Med 1983;; 309:288-296.
39 +
Blackburn H, Keys A, Simonson E, et al:  The electrocardiogram in population study . Circulation 1960;;21:1160-1175.

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