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.