Treatment with low drug doses is generally recommended in the elderly. However, the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined. Therefore, we compared the effect of low-dose with standard dose pravastatin, an HMG CoA reductase inhibitor, on the incidence of cardiovascular events (CVEs) in elderly patients with hypercholesterolemia in a randomized prospective trial. Subjects aged > or = 60 years (73 +/- 6 years) with serum total cholesterol (TC) levels of 220-280 mg/dL were randomized to the low-dose (groupL, 5 mg/day; n=334) or standard dose (groupS, 10-20mg/day; n= 331). Baseline TC levels were similar in the 2 groups (253 +/-15 mg/dL). Patients were followed for 3-5 years (mean 3.9 years). TC levels decreased from baseline by 11-13% in group L and by 15-17% in groupS. TC levels at 1 year in S and L group were 209 +/- 2 mg/ dL (16 +/- 1% decrease) and 221+/- 2 mg/dL (12 +/- 1% decrease), respectively. Forty two and 29 CVEs occurred in group L and S, respectively. The incidence of CVEs was significantly lower in group S than in group L (P = 0.046, generalized Wilcoxon test; P = 0.096, log-rank test). The risk ratio for group S compared with group L was 0.674 (95% confidence interval: 0.423-1.074). Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus, with TC levels of < 253 mg/dL, and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease (P = 0.026, generalized Wilcoxon test; P = 0.032, log rank test). These findings suggest that standard-dose pravastatin (10-20 mg/day) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin (5 mg/ day), especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease.