The Lipid Research Clinics Coronary Primary Prevention Trial Results: I. Reduction in Incidence of Coronary Heart Disease
Abstract
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 less than .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 v 8.6% 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.
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Ezetimibe monotherapy at 10 mg/day reduces LDL-C in hypercholesterolaemic patients by 15-22%, with relatively high interindividual variation.
“In clinical studies, ezetimibe in monotherapy at 10 mg/day reduces LDL-C in hypercholesterolaemic patients by 15-22% with relatively high interindividual variation [261].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [261]
Age, sex, and race have no clinically significant effects on ezetimibe pharmacokinetics, and no dosage adjustment is needed in mild hepatic impairment or mild-to-severe renal insufficiency.
“There are no clinically significant effects of age, sex, or race on ezetimibe pharmacokinetics, and no dosage adjustment is necessary in patients with mild hepatic impairment or mild-to-severe renal insufficiency.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [261]
Life-threatening liver failure with ezetimibe as monotherapy or combined with statins is extremely rare.
“Life-threatening liver failure with ezetimibe as monotherapy or in combination with statins is extremely rare.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [261]
Adding ezetimibe to statin therapy does not appear to increase elevated CK levels beyond those seen with statin treatment alone.
“The addition of ezetimibe to statin therapy does not appear to increase the incidence of elevated CK levels beyond what is noted with statin treatment alone [261].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [261]
Ezetimibe is rapidly absorbed and extensively metabolized to pharmacologically active ezetimibe glucuronide.
“Ezetimibe is rapidly absorbed and extensively metabolized to pharmacologically active ezetimibe glucuronide.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [261]
Clinical trials of bile acid sequestrants demonstrated that LDL-C lowering reduces CV events in hypercholesterolaemic subjects, with benefit proportional to LDL-C reduction.
“In clinical trials, bile acid sequestrants have contributed greatly to the demonstration of the efficacy of LDL-C lowering in reducing CV events in hypercholesterolaemic subjects, with a benefit proportional to the degree of LDL-C lowering.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [239]
In clinical trials, bile acid sequestrants contributed greatly to demonstrating that LDL cholesterol lowering reduces cardiovascular events in hypercholesterolaemic subjects, with benefit proportional to the degree of LDL cholesterol lowering.
“In clinical trials, bile acid sequestrants have contributed greatly to the demonstration of the efficacy of LDL-C lowering in reducing CV events in hypercholesterolaemic subjects, with a benefit proportional to the degree of LDL-C lowering.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [239]
A meta-analysis of large-scale clinical trials involving combination therapy with ezetimibe and statins in patients with high-risk conditions such as FH, ACS, and PAD, confirmed the safety of combination therapy and cardiovascular event suppression resulting from its LDL-C-lowering effects.
“A meta-analysis of large-scale clinical trials involving combination therapy with ezetimibe and statins in patients with high-risk conditions such as FH, ACS, and PAD, confirmed the safety of combination therapy and cardiovascular event suppression resulting from its LDL-C-lowering effects667).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [667]
Orally administered colesevelam lowers HbA1c by 0.5% in diabetes.
“orally administered, colesevelam lowers HbA1c 0.5% in diabetes”
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- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 1984-01-20
- Volume
- 251
- Issue
- 3
- Pages
- 351
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W4248021162
- Cited by
- 2,747
- References
- 0
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 27 · 2023: 19 · 2022: 20 · 2021: 26 · 2020: 17 · 2019: 34 · 2018: 31 · 2017: 33 · 2016: 42 · 2015: 58 · 2014: 51 · 2013: 46 · 2012: 45
- FWCI
- 196.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
- Keywords
- cholestyramine, bile acid sequestrants, primary hypercholesterolemia, type II hyperlipoproteinemia, coronary artery disease, LDL cholesterol, total cholesterol, myocardial infarction, coronary heart disease mortality, cholesterol-lowering diet, cardiovascular risk reduction
- MeSH terms
- Adult, Cholesterol, Cholestyramine Resin, Clinical Trials as Topic, Coronary Disease, Double-Blind Method, Humans, Hypercholesterolemia, Lipoproteins, Male, Middle Aged, Mortality
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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