This paper is only available as a PDF. To read, Please Download here.
Abstract
Recent clinical trials of primary and secondary prevention of cardiovascular disease
have demonstrated that lowering plasma cholesterol decreases the incidence of coronary
heart disease in patients with elevated plasma cholesterol. However, it is not known
whether patients with established coronary artery disease and normal plasma cholesterol
can be benefited. Several previous prevention trials reviewed in this report found
that patients who had plasma cholesterol levels at baseline in the upper portion of
the eligibility range (e.g., >240 mg/dl) received greater benefit from hypolipidemic
diet or drug therapy than patients who had lower plasma cholesterol levels at baseline.
The recent availability of drugs that are more potent and less prone to cause adverse
reactions than previous regimens permits this important question to be addressed.
The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl
coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease
and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and
who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality
are important secondary end points. The trial is enrolling 4,000 men and women from
80 centers throughout North America, age 21 to 75 years, who have survived MI for
3 to 20 months, who have plasma total cholesterol <240 mg/dl (6.2 mmol/ liter) and
low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative
of the general population of patients with MI. Patients are randomized to either active
or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed
to achieve an average decrease in low-density lipoprotein cholesterol of approximately
30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up
will be ≥5 years. To protect against a lower than expected rate of recurrent events,
the trial will be continued until a predetermined fixed number of coronary heart disease
events occurs in the entire cohort so that the original sensitivity of the trial will
be maintained.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Seven Countries Study.Harvard University Press, Boston, MA1980
- Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.N Engl J Med. 1990; 322: 1700-1707
- Cholesterol in the prediction of atherosclerotic disease. New perspectives on the Framingham Study.Ann Intern Med. 1979; 90: 85-91
- Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men.Lancet. 1986; 2: 933-936
- Myocardial ischemia, risk factors and death from coronary heart-disease.Lancet. 1977; 1: 105-109
- Serum lipids and lipoproteins after myocardial infarction: associations with cardiovascular mortality and experience in the Aspirin Myocardial Infarction Study.Am Heart J. 1987; 113: 1356-1364
- Natural history of myocardial infarction in the Coronary Drug Project: long-term prognostic importance of serum lipid levels.Am J Cardiol. 1978; 42: 489-498
- Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH).N Engl J Med. 1990; 323: 946-955
- A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis.Circulation. 1969; 39 and 40: II-1-II-63
- Ischaemic heart disease: a secondary prevention trial using clofibrate.Br Med J. 1971; 4: 775-784
- Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid.Acta Med Scand. 1988; 223: 405-418
- Colestipol hydrochloride in hypercholesterolemic patients — effect on serum cholesterol and mortality.J Chron Dis. 1978; 31: 5-14
- Relation between baseline lipid and lipoprotein values and the incidence of coronary heart disease in the Helsinki Heart Study.Am J Cardiol. 1989; 63: 42H-47H
- A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate.Br Heart J. 1978; 40: 1069-1118
- The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease.JAMA. 1984; 251: 351-364
- Clofibrate and niacin in coronary heart disease.JAMA. 1975; 231: 360-381
- The Oslo Diet-Heart Study. Eleven-year report.Circulation. 1970; 42: 935-942
- Trial of clofibrate in the treatment of ischaemic heart disease. Five-year study by a group of physicians of the Newcastle Upon Tyne region.Br Med J. 1971; 2: 767-775
- The value of lowering cholesterol after MI.N Engl J Med. 1990; 323: 1112-1119
- Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.J Am Coll Cardiol. 1986; 8: 1245-1255
- Report of the Committee of Principal Investigators. W.H.O. Cooperative Trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up.Lancet. 1980; 2: 379-385
- WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up.Lancet. 1984; 2: 600-604
- Lowering cholesterol concentrations and mortality; a quantitative review of primary prevention trials.Br Med J. 1990; 301: 309-314
- The Coronary Drug Project. Findings leading to discontinuation of the 2.5-mg/day estrogen group.JAMA. 1973; 226: 652-657
- The Coronary Drug Project. Findings leading to further modifications of its protocol with respect to dextrothyroxin.JAMA. 1972; 220: 996-1008
- Efficacy and safety of pravastatin in patients with primary hypercholesterolemia.Atherosclerosis. 1990; 85: 219-227
- Safety of pravastatin in long-term clinical trials conducted in the United States.J Drug Dev. 1990; 3: 275-281
- The Lipid Research Clinics Population Studies Data Book. vol. I. The Prevalence Study.in: 5th ed. NIH publication no. 80-1527. U.S. Dept of Health and Human Services, Public Health Service, National Institutes of Health, 1980
- Report of the National Cholesterol Education Program expert panel on detection, evaluation and treatment of high blood cholesterol in adults.Arch Intern Med. 1988; 148: 36-69
- Estimating LDL cholesterol by the Friedwald equation is adequate for classifying patients on the basis of nationally recommended cutpoints.Clin Chem. 1990; 36: 15-19
- Validation of a semi-quantitative food frequency questionnaire: comparison with 1-year diet record.J Am Diet Assoc. 1987; 87: 43-47
- Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol.N Engl J Med. 1990; 323: 224-228
- Pravastatin therapy in primary moderate hypercholesterolaemia: changes in metabolism of apolipoprotein B-containing lipoproteins.J Intern Med. 1990; 227: 81-94
- An aid to data monitoring in long term clinical trials.Controlled Clin Trials. 1982; 3: 311-324
- Stochastically curtailed tests in longterm clinical trials.Communications in Statistics — Sequential Analysis. 1982; 1: 207-219
Article info
Publication history
Accepted:
July 11,
1991
Received:
May 7,
1991
Footnotes
☆This study was supported by a grant from Bristol-Myers Squibb, Princeton, New Jersey.
Identification
Copyright
© 1991 Published by Elsevier Inc.
