HMG CoA Reduction in Patients with Average Cholesterol Concentrations

Abstract

Featured Article: Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–9.4 In 1984, a National Heart, Lung and Blood Institute trial demonstrated that reducing LDL cholesterol (LDL-C)5 with a combination of diet and large doses of the cholesterol-binding resin cholestyramine reduced coronary events (1) and slowed the progression of coronary artery obstruction (2) in men with increased cholesterol concentrations. Resins were not well tolerated, however, and patient compliance was poor. Subsequently, the availability of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HmG CoA) reductase inhibitors changed the approach to cholesterol management, because these drugs were well tolerated and caused marked reductions in total cholesterol (TC) and LDL-C in the majority of individuals. Two important clinical-outcome trials were launched promptly for patients with hypercholesterolemia. The Scandinavian Simvastatin Survival Study (3) enrolled patients with coronary artery disease and hypercholesterolemia [average TC, 261 mg/dL (6.6 mmol/L); average LDL-C, 188 mg/dL (4.87 mmol/L)], and the West of Scotland Coronary Prevention Study (4) used pravastatin in men without clinical coronary disease [average TC, 272 mg/dL (7.0 mmol/L); average LDL-C, 192 mg/dL (5.0 mmol/L)]. On the basis of the earlier findings (1, 2), we assumed that these trials would show clinical benefit; however, patients with the …