Research Clinics Coronary Primary Prevention Research Articles

Sensitivity of exercise electrocardiography for acute cardiac events during moderate and strenuous physical activity. The Lipid Research Clinics Coronary Primary Prevention Trial

Sensitivity of exercise electrocardiography for acute cardiac events during moderate and strenuous physical activity. The Lipid Research Clinics Coronary Primary Prevention Trial

The Lipid Research Clinics Coronary Primary Prevention Trial: design, results, and implications

The Coronary Primary Prevention Trial (CPPT) was the major clinical investigation conducted in the Lipid Research Clinics (LRC) Program. There were 12 North American clinics involved in this joint double-blind protocol. The hypothesis tested was: lowering plasma cholesterol in middle-aged men with primary hypercholesterolemia [plasma total cholesterol greater than or equal to 265 mg/dl (6.88 mm/l)] who are otherwise healthy leads to a reduction in coronary heart disease (CHD) as manifest by a reduction in definite myocardial infarction (fatal and nonfatal) over a 7-year follow-up of all participants. The trial was conducted in 3806 male volunteers between the ages of 35 and 59, who were randomly assigned to two equal groups. The treatment group received a moderate cholesterol-lowering diet plus cholestyramine: the placebo group received an identical diet plus a placebo. The study medication was administered at 24 g daily in divided doses. The participants were followed up bimonthly for an average of 7.4 years. The diet (daily cholesterol intake of about 400 mg and a polyunsaturated fat/saturated fat ratio of 0.8) lowered plasma cholesterol by an average of 4%, as designed. The cholestyramine group experienced average plasma total cholesterol (TC) lowering and plasma low-density lipoprotein cholesterol (LDC-C) lowering 8.5% and 12.6% greater than the placebo group, respectively. This resulted in a 19% reduction in definite myocardial infarction (P less than 0.05). The trial results for CHD deaths, nonfatal myocardial infarction,new positive exercise stress tests (P less than 0.001) new-onset angina (P less than 0.01) and coronary artery bypass surgery (P less than 0.06) and coronary artery bypass surgery ((p less than 0.06) were consistent with and supportive of the main findings of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

The lipid research clinics coronary primary prevention trial: Design, results, and implications

The lipid research clinics coronary primary prevention trial: Design, results, and implications

Deaths due to Accidents and Violence in Two Recent Trials of Cholesterol-Lowering Drugs

The Helsinki Heart Study and the Lipid Research Clinics Coronary Primary Prevention Trial both reported higher rates of deaths due to homicides, suicides, and accidents in the groups receiving cholesterol-lowering agents compared with the groups receiving placebos. We examined these deaths in the active treatment arms of the two trials to determine if there were some readily explainable causes or if the cholesterol-lowering agents might be a factor. Our examination showed that the two homicides were victims, not offenders, and one had stopped treatment because of myocardial infarction 1 year before his death. Five of the eight suicides had dropped out of the trials and had not taken the cholesterol-lowering drugs for periods of months to years prior to committing suicide. Of the 10 deaths due to accidents, two were dropouts from the trials, three others had high blood alcohol concentrations detectable at autopsy, and another three reported a history of psychiatric symptoms and/or treatment prior to entry. When dropouts and known risk factors for these deaths such as alcohol intoxication and psychiatric histories are considered, little evidence remains to support the hypothesis that cholesterol-lowering drugs are causally associated with deaths due to homicides, suicides, and accidents in these trials.

Variations in cardiovascular disease mortality by time and place: the challenge

Australian and New Zealand Journal of MedicineVolume 20, Issue 5 p. 636-638 Free Access Variations in cardiovascular disease mortality by time and place: the challenge ROBERT BEAGLEHOLE, ROBERT BEAGLEHOLE Professor, Department of Community Health, School of Medicine, University of Auckland, Auckland, New ZealandSearch for more papers by this author ROBERT BEAGLEHOLE, ROBERT BEAGLEHOLE Professor, Department of Community Health, School of Medicine, University of Auckland, Auckland, New ZealandSearch for more papers by this author First published: October 1990 https://doi.org/10.1111/j.1445-5994.1990.tb00391.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 WHO MONICA Project Principal Investigators (Prepared by H. Tunstall-Pedoe). WHO MONICA Project (Monitoring Trends and Determinants in Cardiovascular Disease): a major international collaboration. J Clin Epidemiol 1988; 41: 105– 14. 2 Rose G. Cold weather and ischaemic heart disease. Br J Prev Soc Med 1966; 20: 97– 100. 3 Anderson TW, Le Riche WH. Cold weather and myocardial infarction. Lancet 1970; 1: 291– 6. 4 McKee CM. Deaths in winter: can Britain learn from Europe Eur J Epidemiol 1989; 5: 178– 82. 5 Scragg R. Seasonal variation of mortality in Queensland. Community Health Studies 1982; 6: 120– 9. 6 Marshall RJ, Scragg R, Bourke P. An analysis of the seasonal variation of coronary heart disease mortality in New Zealand. Int J Epidemiol 1988; 17: 325– 31. 7 Dunningan MG, Harland WA, Fyfe T. Seasonal incidence and mortality of ischaemic heart disease. Lancet 1970; ii: 793– 7. 8 Thakur CP, Anand MP, Shahi MP. Cold weather and myocardial infarction. Int J Cardiol 1987; 16: 19– 25. 9 Brennan PJ, Greenberg G, Miall WE, Thompson SG. Seasonal variation in arterial blood pressure. Br Med J 1982; 285: 919– 23. 10 Gordon DJ, Trost DC, Hyde J, Whaley FS, Hannan PJ, Jacobs DR. Seasonal cholesterol cycles: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. Circulation 1987; 76: 1224– 31. 11 Beaglehole R, Dobson A, Hobbs MST, Jackson R, Martin CA. Coronary heart disease in Australia and New Zealand. Int J Epidemiol 1989; 18(Suppl 1): S145– 8. 12 Gibberd RW, Dobson AJ, Florey C du V, Leeder SR. Differences and comparative declines in ischaemic heart disease mortality among subpopulations in Australia, 1969–78. Int J Epidemiol 1984; 13: 25– 31. 13 West RR, Lowe CR. Mortality from ischaemic heart disease—inter-town variation and its association with climate in England and Wales. Int J Epidemiol 1976; 5: 195– 201. 14 Keatinge WR, Coleshaw SRK, Cotter F, Mattock M, Murphy M, Chelliah R. Increases in platelets and red cell counts, blood viscosity, and arterial pressure during mild surface cooling: factors in mortality from coronary and cerebral thrombosis in winter. Br Med J 1984; 289: 1405– 8. 15 Anderson TW, Rochard C. Cold snaps, snowfall and sudden death from ischemic heart disease. Can Med Assoc J 1979; 121: 1580– 3. 16 Glass RI, Zack MM. Increase in deaths from ischaemic heart disease after blizzards. Lancet 1979; i: 485– 7. 17 Voors AW, Johnson WD. Altitude and arteriosclerotic heart disease mortality in white residents of 99 of the 100 largest cities in the United States. J Chron Dis 1979; 32: 157– 62. 18 West R. Seasonal variation in CHD mortality. Int J Epidemiol 1989; 18: 463– 4. 19 Bainton D, Jones GR, Hole D. Influenza and ischaemic heart disease - a possible trigger for acute myocardial infarction Int J Epidemiol 1978; 7: 231– 9. 20 Scragg R. Seasonally of cardiovascular disease mortality and the possible protective effect of ultra-violet radiation. Int J Epidemiol 1981; 10: 337– 41. 21 Scragg R, Jackson R, Holdaway IM, Lim T, Beaglehole R. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol (in press). Volume20, Issue5October 1990Pages 636-638 ReferencesRelatedInformation

Lovastatin and simvastatin prevention studies

There is substantial evidence that drug treatment of hypercholesterolemia in patients without known coronary artery disease (CAD) can reduce fatal and nonfatal CAD events. Two trials, the Lipid Research Clinics Coronary Primary Prevention Trial and the Helsinki Heart Study used cholestyramine and gemfibrozil, respectively, to alter lipoprotein levels; their demonstrated efficacy and safety have led to their widespread use in hyperlipidemic patients. Recently, a new class of hypolipidemic agents has been shown to be extremely effective in lowering total and low-density lipoprotein cholesterol levels. These drugs, including lovastatin and simvastatin, competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of intracellular cholesterol synthesis. Results of safety and efficacy studies suggest that they may be valuable first-line treatment options for high-risk hypercholesterolemic patients. Two long-term clinical trials are planned with lovastatin and simvastatin. In the United States, lovastatin will be used in a double-blind, placebo-controlled, primary prevention trial involving 8,000 patients without clinical evidence of CAD, slight to moderate elevations of total cholesterol, and low-and high-density lipoprotein cholesterol to establish whether 5 years of treatment will decrease the rate of fatal CAD or nonfatal myocardial infarction. A Scandinavian study of 4,000 patients with ischemic heart disease and hypercholesterolemia will determine if simvastatin will improve total survival and reduce fatal or nonfatal myocardial infarction and sudden death for at least 3 years. These study designs will be discussed and compared with other studies, and the expected impact on CAD event rates presented.

Clinical Relevance of hyperlipidemia

This review concerns the clinical impact of treating hyperlipidemia. The U.S. Lipid Research Clinics Coronary Primary Prevention Trial, the Helsinki Heart Study, and the Oslo Primary Prevention Trial all consistently showed that intensive and long-term (5-7 years) lipid-lowering treatment is successful in reducing the incidence of fatal and nonfatal myocardial infarction. Secondary prevention trials (Coronary Drug Project and the Stockholm Ischaemic Heart Disease Secondary Prevention Study) have overall confirmed this result. Assessment of progression/regression of atherosclerosis by invasive or noninvasive methods has shown that an important mechanism underlying the reduction of coronary events with long-term lipid-lowering treatment is that involving stabilization or regression of arterial lesions. An additional advantage from lipid-lowering treatment might come from useful hemodynamic changes, occurring shortly after the start of an intensive cholesterol-lowering treatment with low-density lipoprotein apheresis.

Clinical trials including an update on the Helsinki heart study

The incidence of myocardial infarction (MI), sudden death and other clinical manifestations of coronary heart disease can be reduced by lowering the blood cholesterol level. This is now well established by multiple clinical trials using a variety of interventions including diet and lipid-lowering drugs. Dietary studies in Los Angeles and in Oslo, Norway, have induced a reduction in blood cholesterol of between 10 and 15% with correlated reductions in coronary disease of 20 to 50%. Both niacin and clofibrate in separate cohorts demonstrated a significant reduction in new MI during 5 years of treatment in the Coronary Drug Project. Similar reductions in new MI occurred in the World Health Organization Study with clofibrate. However, in this trial and different from all other trials, mortality in the drug-treatment group actually increased. This finding remains unexplained. In the more recent Lipid Research Clinics Coronary Primary Prevention Trial using the bile acidbinding resin cholestyramine, only a 9% reduction in total cholesterol resulted in a highly significant reduction in the major end points—MI and sudden death—as well as in other secondary end points, including the need for coronary artery bypass graft surgery, ischemic changes on exercise electrocardiography and new-onset angina. Recently, another primary prevention trial using gemfibrozil produced a similar reduction in total cholesterol but a much more significant increase in high-density lipoprotein cholesterol. The reduction in coronary heart disease was in excess of 34% and was strongly related to both low-density lipoprotein cholesterol reduction and high-density lipoprotein elevation. Combination drug studies have produced larger reductions in total cholesterol. In the Stockholm Heart Study, niacin and clofibrate produced a statistically significant reduction in total mortality in patients who had had recent Ml. Similarly, in men who had undergone coronary artery bypass graft surgery, the combination of niacin, colestipol and diet produced strong evidence of a reduced rate of progression of arteriosclerotic lesions as demonstrated by coronary angiography. This study, conducted at the University of Southern California, was the Cholesterol-Lowering Atherosclerosis Study. It also produced evidence of lesion regression in some patients. Although these studies have been carried out primarily in middle-aged men, the older segments of these populations have appeared to do as well with regard to disease prevention as the younger members of the cohorts. We can now treat patients with high blood cholesterol levels both before and after manifestation of coronary disease with significant assurance that beneficial effects will accrue. Additional studies with newer and more powerful lipid-lowering agents are needed, as are studies in women and the elderly.

Are Clinical Trials Cost-effective?

To the Editor.— In the October 6 issue of JAMA , Dr Detsky 1 performed a cost-effective analysis of seven selected clinical trials and calculated the incremental cost-effectiveness for performing these trials, expressed as dollars per life-year extended. He concluded that this selected group of clinical trials was a good investment and suggested that government policymakers consider this information when allocating funds for medical research. I agree with Dr Detsky that the selected trials were a good investment but disagree that they were cost-effective from the standpoint of number of years of life saved. The combined cost of all seven trials selected was $272 million. Two primary prevention trials selected, the Lipid Research Clinics-Coronary Primary Prevention Trial and the Multiple Risk Factor Intervention Trial, cost $260 million and, therefore, represent 96% of the total cost of all seven trials selected. Unfortunately, life was not extended in either of these primary prevention

Empirical Bayes estimates of subgroup effects in clinical trials

At the completion of a clinical trial it is often desirable to compare the treatments within subgroups of patients. The results of the subgroup analysis are usually reported for the subgroups within which sizable treatment differences are found. This practice can lead to an overestimate of the difference between treatments within the subgroups reported. One way of adjusting for this bias is to use empirical Bayes methods which shrink the extreme estimates toward the overall measure of treatment difference. Both point and interval estimates can be obtained. The computations are illustrated with an example using subgroup data from the Lipid Research Clinics Coronary Primary Prevention Trial.

Serum lipoproteins as risk factors: recent epidemiologic studies in individuals with and without prevalent cardiovascular disease

Contrary to most prospective epidemiologic studies, an earlier report from the British Regional Heart Study (BRHS) suggested that high density lipoprotein (HDL)-cholesterol in men aged 40-59 years was not a significant, independent, predictive risk factor for coronary heart disease (CHD), controlling for the composite of low density lipoprotein (LDL)--plus very low density lipoprotein--cholesterol (i.e. non-HDL-cholesterol) and for other risk factors. In response to that report, a systematic re-examination of the Framingham Heart Study, the Lipid Research Clinics Prevalence Mortality Follow-up Study, the Lipid Research Clinics-Coronary Primary Prevention Trial, and the Multiple Risk Factor Intervention Trial was undertaken to compare the results of these four studies with those of the BRHS. In white men and women aged 30-69 years and free of clinical symptoms of CHD at baseline, the incidence of CHD in all four studies was generally highest in those with a low HDL-cholesterol and lowest in those with a high HDL-cholesterol. A later report from the BRHS, with longer follow-up and increased number of CHD events, controlling for other risk factors but without controlling for combined non-HDL-cholesterol, disclosed a statistically significant, independent prediction of CHD, albeit of modest magnitude, by HDL-cholesterol. Data from the USSR Lipid Research Clinics Follow-up Study differed from the American and the British studies. Despite higher HDL-cholesterol levels, CHD mortality rates were as high (or higher) in the USSR than in the US Lipid Research Clinics.(ABSTRACT TRUNCATED AT 250 WORDS)

The Purity of Cholestyramine Resin-Reply

In Reply.— As pointed out in the original report of the Lipid Research Clinics Coronary Primary Prevention Trial results,1the total incidence of fatal and nonfatal malignant neoplasms was similar in the cholestyramine resin and placebo groups. These incidence rates were somewhat lower than overall US cancer rates for comparably aged men. However, when the many different categories of malignancies were examined, the combined incidence of cancers of the mouth, pharynx, gastrointestinal tract, and pancreas was somewhat greater (21 vs 11 cases) in the cholestyramine resin group than in the placebo group. This excess incidence of gastrointestinal tract cancers was offset by reduced incidence of other cancers, particularly of the lung and prostate. The small numbers and multiple categories precluded firm conclusions, although the observation of excess cancers in the organ system directly exposed to cholestyramine resin was a matter of concern, especially in view of animal experiments in

The Purity of Cholestyramine Resin-Reply

In Reply. — We are pleased to respond to the questions about Questran raised by Dr Goldstein by assuring him that (1) the cholestyramine resin used in the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) was not contaminated, (2) currently marketed Questran is free of contamination, and (3) although a temporal association between cholestyramine resin and certain tumors has been observed, a causal relationship has not been established after more than 20 years of commercial availability and several hundred thousand patient-years of therapy dispensed. The questions asked by Dr Goldstein appear to arise from the fact that, in April 1988, Bristol Laboratories initiated a recall because it determined that certain batches of bulk cholestyramine resin supplied by Rohm & Haas and used in the production of Questran contained very low levels of the agricultural chemicals dichlorodiphenyldichloroethylene and dichlorobenzophenone. These chemicals are related to the manufacture of a pesticide (dicofol)

Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: The lipid research clinics coronary primary prevention trial

A positive exercise electrocardiogram (ECG) has been proved to predict cardiovascular events in asymptomatic normolipidemic men. To study whether it is also predictive for hypercholesterolemic men, data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed. All the men had performed a submaximal treadmill exercise test at baseline, before they were assigned to the cholestyramine or placebo treatment group. Because of missing or inconclusive data, 31 men were excluded from the analyses. A test was positive if the ST segment was displaced by ≥1 mm (visual code) or there was ≥10 μV-s change in the ST integral (computer code), or both. The prevalence of a positive test was 8.3%.During the 7 to 10 year (mean 7.4) follow-up period, the mortality rate from coronary heart disease was 6.7% (21 of 315) in men with a positive test and 1.3% (46 of 3,460) in men with a negative test (placebo and cholestyramine groups combined). The age-adjusted rate ratio for a positive test, compared with a negative test, was 6.7 in the placebo group and 4.8 in the cholestyramine group. With use of Cox's proportional hazards models, it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age, smoking history, systolic blood pressure, high density lipoprotein cholesterol and low density lipoprotein cholesterol. A positive test was not significantly associated with nonfatal myocardial infarction.Thus, the results indicate that the exercise ECG response is a valuable and independent predictor of the risk of death from coronary heart disease in hypercholesterolemic men.

Reduction in coronary heart disease: clinical and anatomical considerations.

Coronary artery bypass surgery, percutaneous transluminal coronary angioplasty and thrombolytic therapy in acute myocardial infarction have relieved symptoms, preserved myocardium, and prolonged life but have not modified the progression of atherosclerosis in the coronary arteries. In the last 10 years, however, progress has been made in establishing the cholesterol-atherogenesis hypothesis. Epidemiologic studies have demonstrated that the higher the total plasma cholesterol and low density lipoprotein cholesterol (LDL-C), the greater the risk that coronary artery disease will develop. Recently, clinical trials including the Coronary Drug Project, the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), and the Helsinki Heart Study provided evidence that lowering cholesterol reduces the frequency of fatal and nonfatal coronary events. In addition, the National Heart, Lung, and Blood Institute (NHLBI) Type II Coronary Intervention Study and the Cholesterol Lowering Atherosclerosis Study demonstrated that lowering of cholesterol was associated with a decreased incidence of progression of coronary disease, as well as with the potential for reduction in the atherosclerotic plaque. Beneficial effects of diet and lifestyle changes also have an important effect on atherosclerosis. The impact of lowering cholesterol has been limited primarily by pharmacologic programs which lower cholesterol only 10-20% and are associated with a high incidence of intolerable side effects. With the recent introduction of the HmG co-A reductase inhibitors and their more profound effect on serum lipids, it may be possible to further promote plaque regression. The future of all these interventions, however, must still be assessed by overall mortality; studies to date have demonstrated beneficial effects on cardiovascular mortality but age-adjusted total mortality has remained unchanged. Future management of patients with acute and chronic coronary artery disease will involve a collaboration of cardiologists, endocrinologists, and epidemiologists to coordinate screening, recognition, and treatment of this disease.

Current Therapy for Hypercholesterolemia

THE EVIDENCE is now in that lowering cholesterol levels reduces the risk of coronary heart disease (CHD). A century of animal data as well as morphological, genetic, and metabolic studies in man point to a strong association between serum cholesterol levels and coronary artery disease. Prospective epidemiologic studies show a graded relationship between serum cholesterol and coronary risk extending to cholesterol levels below 4.14 mmol/L ( 1 Clinical trials performed in man provide the final validation of the cholesterol-atherogenesis connection. In the Lipid Research Clinics Coronary Primary Prevention Trial, over a 7-year period a 12.5% decrease in low-density lipoprotein (LDL) cholesterol levels was associated with a 19% decrease in the incidence of myocardial infarction and CHD death. 2,3 In addition, treatment was associated with a significant reduction in the development of angina, a positive exercise test, and the need for

The AMA's Campaign Against Cholesterol-Reply

In Reply. — The letter by Dr Stare takes issue with the Campaign Against Cholesterol announced recently by the American Medical Association (AMA). Dr Stare objects to the campaign on the basis that the cholesterol factor is of minor importance as a risk factor in cardiovascular disease and suggests that our efforts might be directed in different ways. That cholesterol is of minor importance as a risk factor for cardiovascular disease is a subjective opinion. The recent report of the expert panel organized by the National Cholesterol Education Program certainly supports the contention that reducing the level of cholesterol is an important means of reducing morbidity and mortality from cardiovascular disease. Many well-designed studies, including the Lipid Research Clinics Coronary Primary Prevention Trial, the Framingham Study, and the Multiple Risk Factor Intervention Trial, indicate that elevated levels of blood cholesterol contribute to early death from coronary heart disease. In fact,

Importance of coronary heart disease risk factors in the management of hypertension: An overview

In the United States, the number of deaths due to coronary heart disease has declined progressively since the early 19’70s in part as a result of the treatment of hypertension. Nevertheless, the overall mortality rate from coronary heart disease in this country remains high; moreover, in a number of cases its first clinical sign is sudden death. Because of this, investigators have spent years conducting a wide range of epidemiologic and clinical studies in an attempt to identifv the factors responsible for coronary atherosclero&. Results of these st,udies demonstrate that cigarette smoking, elevated levels of total cholesterol in the plasma, and hypertension are major risk factors for coronary heart disease. In the last few years, the relationship among these three major risk factors for coronary heart disease has received considerable attention. Although each risk factor can contribute to the development of atherosclerosis, the interaction among risk factors complicates the clinician’s efforts to select the most appropriate treatment and prevention regimens. In the Framingham Heart Study, for example, investigators found that there is a powerful interaction between two of the major risk factors: hypertension and elevated serum cholesterol levels. The benefits of effective management of one factor, such as high blood pressure, may be offset or negated by adverse effects on lipid levels Ill. As such, physicians should monitor both blood pressure and cholesterol levels to ensure that good control of the former does not have an unfavorable effect on the latter. Similarly, results of the Lipid Research Clinics Coronary Primary Prevention Trial have clearly demonstrated the benefits of lowering cholesterol levels [a]. In fact, this study, which was carried out in approximately 3,800 patients, provided strong evidence that a 1 percent reduction in cholesterol levels reduces the risk of death due to myocardial infarction by 2 percent. Finally, within the last year, the report of an expert panel of the National Cholesterol Education Program provided new guidelines for the treatment of high blood cholesterol levels in adults 20 years of age and over. The panel classified total cholesterol levels as follows: 200 mgidl or less is desirable; between 200 and 239 mgidl indicates borderline-high bloocl cholesterol levels; and 240 mgidl or more signifies high blood cholesterol levels 131. Based on the results of these and other findings,

Lovastatin vs Cholestyramine Therapy for Primary Hypercholesterolemia

To the Editor.— A multicenter study 1 published in the July 15 issue of JAMA compared lovastatin and cholestyramine resin for treating severe primary hypercholesterolemia and concluded that lovastatin was both more effective and better tolerated. There is no argument that lovastatin is better tolerated than cholestyramine; however, I am not convinced that it is more effective. The Lipid Research Clinics Coronary Primary Prevention Trial 2 and the more recently published Helsinki Heart Study 3 —both long-duration primary prevention trials—demonstrated that coronary heart disease morbidity and mortality can be reduced by favorably altering lipoprotein levels using cholestyramine in the former and gemfibrozil in the latter trial. Unfortunately, neither trial resulted in a decrease in overall mortality in the groups receiving drug treatment. Fifteen-year follow-up of a secondary prevention trial 4 did reveal a decrease in coronary heart disease mortality and overall mortality in the niacin-treated group. Cholestyramine, gemfibrozil, and niacin

Therapeutic control of hyperlipidemia in the prevention of coronary atherosclerosis: A review of results from recent clinical trials

The link between elevated plasma cholesterol levels and coronary atherosclerosis is now well established. During the past decade, results from therapeutic trials indicate that control of hypercholesterolemia does result in lower cardiovascular risk. Many of these results were obtained in hypercholesterolemic, middle-aged men. Comparable data in women are not available but it is inferred that they would also benefit from cholesterol reduction. Results from the Coronary Drug Project, extended over 15 years, indicate that lipid-lowering therapy with niacin for 5 years was associated with a decrease in total mortality as well as mortality from coronary heart disease. In the studies performed for shorter periods (5 to 7 years), therapy lowered only cardiovascular morbidity and mortality but had no beneficial effect on total mortality. A reduction in cardiovascular risk begins to appear 24 to 28 months after the initiation of therapy and continues to accrue thereafter. The relatively uniform results from recent large-scale clinical trials (Lipid Research Clinics Coronary Primary Prevention Trial, Coronary Drug Project, Helsinki Heart Study) indicate that cholesterol reduction, per se, probably explains the lower cardiovascular morbidity and mortality observed in these trials. As a result of these trials, recent redefinitions of hypercholesterolemia and more aggressive treatment programs have been recommended. These guidelines stress assessment of all cardiovascular risk factors and recommend individualized care of the patient. To control hypercholesterolemia, conservative measures with diet are recommended before therapy with medication is considered. Recent clinical trial experience indicates that the clinician can have significant impact on atherosclerosis by identifying and treating patients with plasma cholesterol levels in the high-risk range.