Clinical trials: surrogate endpoints or hard endpoints?

A man, aged 50, has about a 50% risk and a 50-year-old woman a 35% risk of having a myocardial infarction during their lifetime. The extent of atherosclerosis is the primary determinant of the risk of myocardial infarction. We will be unable to substantially reduce the lifetime risk of coronary artery disease without primary prevention of atherosclerosis. Noninvasive methods to measure subclinical atherosclerosis and its progression offer a unique opportunity to improve individual patient preventive strategies, based both on pharmacologic and nonpharmacologic therapies, as well as an opportunity to study and develop new drug therapies. The use of subclinical disease as a surrogate marker of atherosclerosis and the study of plaque characteristics will greatly enhance our understanding of the role of new risk factors for atherosclerosis, lipoprotein metabolism, and genetic-lifestyle interactions.