Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia

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. (N Engl J Med 1995;333:1301-7.) From the Departments of Pathological Biochemistry (J.S., C.J.P.), Medical Cardiology (S.M.C., A.R.L., P.W.M.), and Medicine (J.H.M.), University of Glasgow and Royal Infirmary, Glasgow; Robertson Centre for Biostatistics, University of Glasgow, Glasgow (I.F.); and the Department of Medicine, Dumfries and Galloway District General Hospital, Dumfries (C.G.I.) — all in Scotland. Address reprint requests to Dr. Ford at the Robertson Centre for Biostatistics, Boyd Orr Bldg., University of Glasgow, Glasgow G12 8QQ, Scotland. Supported by a research grant from the Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J. *The members of the West of Scotland Coronary Prevention Study Group are listed in the Appendix. E ARLIER trials of lipid-lowering drugs in the primary prevention of coronary heart disease have demonstrated that lowering cholesterol levels in middle-aged men with hypercholesterolemia reduces the incidence of myocardial infarction. 1-4 However, these studies, because of their design and low rates of observed events, were unable to show a clear effect of therapy on the risk of death from coronary heart disease or death from any cause. A meta-analysis of the trials provided support for the likelihood that therapy lowered the risk of death from coronary heart disease, but it also aroused concern that the risk of death from noncardiovascular causes might be increased by treatment. 5-8 Whether this latter association was due to chance, to the reduction in cholesterol itself, or to an adverse effect of the drugs is not clear. Recently, a new class of lipid-lowering drug, the 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors, has been introduced into clinical practice. These drugs block endogenous synthesis of cholesterol and reduce the levels of low-density lipoprotein (LDL) cholesterol. They slow the progression of coronary disease and reduce the incidence of death from coronary causes and death from any cause in men with manifest coronary heart disease. 9-15 The present study was designed to evaluate the effectiveness of a reductase inhibitor, pravastatin (Pravachol), in preventing coronary events in men with moderate hypercholesterolemia and no history of myocardial infarction.