Cholesterol, primary and secondary prevention, and all-cause mortality

Clinical trials of cholesterol lowering in apparently healthy persons (primary prevention) and in persons with known coronary disease (secondary prevention) routinely show a decrease in the incidence of nonfatal and fatal coronary events. Primary prevention trials, however, generally have failed to show a beneficial effect of cholesterol lowering on total mortality, because of both low overall death rates and a disturbingly high number of deaths from noncoronary causes in the treatment groups. Studies of secondary prevention give more clear-cut evidence of benefit. The rate of death from coronary heart disease is extremely high in these studies, overwhelming the rates for other causes of death. Thus, a possible increase in noncoronary deaths is of much less concern in secondary prevention studies. A possible link between cholesterol lowering and noncoronary causes of death should be explored using dose-response analyses of existing data sets, in both individual studies and aggregate meta-analysis; such analyses should be similar to those that have been done to study the relation between cholesterol lowering and coronary events. These analyses would greatly assist us in developing safe, efficacious ways to prevent coronary heart disease.