Primary prevention of coronary heart disease by lowering lipids: results and implications

Evidence to support the hypothesis that lowering total and low-density lipoprotein (LDL) cholesterol may reduce heart attacks and heart deaths has, until recently, not been available. Early primary prevention trials lacked definitive data on these "hard" end points. Since 1980, five primary prevention trials have attempted to demonstrate the benefit of lowering cholesterol. Three of these involved diet: the Oslo Heart Trial and both the European and American Multiple Risk Factor Intervention Trials (MRFITs). Two involved lipid-lowering drugs: the European Clofibrate Primary Prevention Trial and the National Heart, Lung, and Blood Institute's recently concluded Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). The Olso Heart Trial suggested a benefit from the dietary reduction of cholesterol; results of the other studies of diet were equivocal. Although clofibrate did demonstrate a reduced incidence of heart attacks in the treated group, the cardiac mortality rate was not altered in this group. A significant increase in the all-cause mortality rate (other than ischemic heart disease) observed in this trial in treated subjects makes clofibrate difficult to recommend. The LRC-CPPT study, involving cholestyramine, has provided conclusive evidence concerning the benefits of lowering cholesterol: significant reductions were observed in all cardiovascular end points measured, including the development of angina and positive exercise stress tests, referral for bypass surgery, and the hard primary study end point heart attack and heart attack death.