CLINICAL IMPLICATIONS OF RECENT CHOLESTEROL-LOWERING TRIALS FOR THE SECONDARY PREVENTION OF CORONARY HEART-DISEASE

Coronary risk factors, including hypercholesterolemia, contribute subs tantially to the development and clinical expression of atherosclerosi s. Of all patients, those with established coronary heart disease bene fit the most from risk factor modification (secondary prevention). Ove r the past 2 decades, 18 of 19 angiographic cholesterol lowering trial s have demonstrated slowing of the progression of coronary or carotid atherosclerosis. Three important trials completed in the last 2 years have clarified the clinical benefit that can be derived from cholester ol lowering. All th ree also demonstrate findings that support the Nat ional Cholesterol Education Program (NCEP) guidelines. These are the S candinavian Simvastatin Survival Study (4S), the Cholesterol and Recur rent Events (CARE) trial, and the Post-Coronary Artery Bypass Graft (P ost-CABG) trial. The 4S and CARE trials demonstrated 24% to 40% reduct ions in total and cardiovascular mortality and morbidity, less need fo r coronary revascularization procedures, and fewer hospitalizations. C oronary disease patients with a total cholesterol level of >200 mg/dL or low-density lipoprotein cholesterol (LDL-C) levels of >125 mg/dL sh owed clear benefit from simvastatin or pravastatin. This benefit appea red to be independent of age, gender, other risk factors, and other me dications. The Post-CABG trial demonstrated less arteriographic diseas e progression in patients undergoing aggressive versus moderate choles terol reduction. Recent advances in our understanding of coronary athe rosclerosis pathophysiology suggest that cholesterol lowering reduces cardiovascular events through improvements in endothelial function, re ductions in oxidized LDL-C and reductions in plaque inflammation. Thes e factors result in less atherosclerosis progression and more plaque s tability. Unfortunately, only about 25% of coronary heart disease pati ents are currently on cholesterol lowering drugs. The same treatment g ap exists for other risk factor modifications. These data suggest an i mportant opportunity exists to improve the care of coronary disease pa tients.