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Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Open accessAbstract
BACKGROUND: Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS: We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS: Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS: Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.
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“The 2 classic trials of primary prevention patients published in the 1990s showed a reduction in morbidity but not mortality.2,3”
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“However, the current recommendations are predominantly derived from clinical trials conducted several decades ago during the initial development of statins to reduce low-density lipoprotein cholesterol (LDL-C) levels.2,3”
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“Large-scale epidemiologic and clinical studies have shown that lowering of low-density lipoprotein cholesterol (LDL-C) levels through pharmacologic and/or non-pharmacologic means is associated with significant CV benefits, with each mmol/L reduction in LDL-C levels leading to an approximately 30% reduction in the risk of adverse CV events [5][6][7][8][9][10].”
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Metadata
- Authors
- Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J.
- Affiliations
- Glasgow Royal Infirmary (GB)
- University of Glasgow (GB)
- NHS Dumfries and Galloway (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1995-11-16
- Volume
- 333
- Issue
- 20
- Pages
- 1301-1308
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2155598961
- Semantic Scholar
- 1aa5f64bbe1d0c4c74fc3de7c89ac2dffb48630a
- Cited by
- 7,449
- References
- 26
- Citations by year
- 2026: 31 · 2025: 33 · 2024: 56 · 2023: 54 · 2022: 66 · 2021: 72 · 2020: 95 · 2019: 90 · 2018: 108 · 2017: 121 · 2016: 157 · 2015: 137 · 2014: 177 · 2013: 215 · 2012: 197
- FWCI
- 344.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- pravastatin, hypercholesterolemia, coronary heart disease prevention, statins, LDL cholesterol lowering, nonfatal myocardial infarction, cardiovascular mortality, men, cholesterol-lowering therapy
- MeSH terms
- Anticholesteremic Agents, Cholesterol, Coronary Disease, Double-Blind Method, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Neoplasms, Risk, Incidence, Survival Analysis, Pravastatin
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