Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels
Authors: John R. Downs, Michael Clearfield, Stephen Weis, Edwin Whitney, Deborah R. Shapiro, Polly A. Beere, Alexandra Langendorfer, Evan A. Stein, William Kruyer, Antonio M. Gotto, Jr, None for the AFCAPS/TexCAPS Research Group
Journal: JAMA (1998)

Context.-Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons.Objective.-Tocompare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels.Design.-A randomized, double-blind, placebo-controlled trial.Setting.-Outpatientclinics in Texas.Participants.-Atotal of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age-and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III).Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile).Intervention.-Lovastatin(20-40 mg daily) or placebo in addition to a lowsaturated fat, low-cholesterol diet.Main Outcome Measures.-Firstacute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death.Results.-After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (183 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79;PϽ.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83;P = .002),unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95;P = .02),coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85;P = .001),coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92;P = .006),and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91;P = .003).Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL).There were no clinically relevant differences in safety parameters between treatment groups.Conclusions.-Lovastatinreduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels.These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.