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.— To compare 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.— Outpatient clinics in Texas.
Participants.— A total 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 
mg/dL) (51st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150
 mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L
(36  mg/dL) for men and 1.03 (0.14) mmol/L (40  mg/dL) for women (25th
and 16th percentiles, respectively), and median (SD) triglyceride levels were
1.78 (0.86) mmol/L (158  mg/dL) (63rd percentile).
Intervention.— Lovastatin (20-40 mg daily) or placebo in addition to a low–saturated
fat, low-cholesterol diet.
Main Outcome Measures.— First acute 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; P<.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.— Lovastatin reduces 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.