We found no differences in noncardiovascular mortality rates in the older patients in the CARE trial, as shown in the Table. However, there was an overall mortality benefit for the older patients in the CARE trial. The CARE cohort of older and younger patients (1) was not powered for a mortality end point, but with the increased event rate in the older patients we saw a significant decrease in total and cardiovascular mortality rates in the older group.

Dr. Bannerman addresses the differences in breast cancer incidence between the women who received pravastatin and those who received placebo in the overall CARE trial (1). We explored this finding carefully and concluded that this difference was a statistical aberration, with an unexpectedly low incidence of new breast cancer in the placebo group. Although epidemiologic data in the United States and Canada, where the trial was conducted, would predict 5 cases of new invasive breast cancer (95% CI, 0.6 to 9.3 cases), no new cases of invasive breast cancer were reported in the 290 women in the placebo group during the 5 years of the trial. The 1 reported case of breast cancer in the placebo group was metastatic from a previously treated cancer. In contrast, the number of new cases of invasive breast cancer in the pravastatin group, 8, was closer to the expected number, 5, and was within the confidence interval. These results strongly suggest that the inequality in breast cancer incidence between the groups is due to chance rather than a biological effect of pravastatin. This is supported by findings in the LIPID trial (2), which included 2.5 times the number of women in the CARE trial and had a longer median follow-up (5.9 years, compared to 4.9 years for CARE). The incidence of breast cancer did not differ between the placebo and pravastatin groups in LIPID (10 cases in each group). Findings were similar for long-term trials that used other statin drugs (3-5).

The analysis of the older patients in the CARE trial showed no increase in the risk for noncardiovascular death in the pravastatin group compared with the placebo group. However, the benefits of pravastatin treatment for older patients with coronary disease are substantial, with a 39% reduction in risk for death from coronary artery disease or nonfatal myocardial infarction (CI, 18% to 55%), a 32% reduction (CI, 15% to 46%) in recurrent coronary events, and a 40% reduction (CI, 4% to 62%) in stroke. Rate of death from coronary heart disease was reduced by 45%, and the total mortality rate decreased by 30%.

Older patients constitute a population in which data for cardiovascular event reduction have been limited even though this condition is the leading cause of morbidity and death in this group. The results of the CARE trial show unequivocal benefits with no offsetting adverse effects of pravastatin to prevent recurrent coronary events and stroke and to improve survival in older patients with myocardial infarction.