Clinical trial endpoints: angiograms, events, and plaque instability.

Clinical trials provide evidence on methods for risk assessment of coronary artery disease and on interventions used to decrease risk. Plaque rupture, which leads to either progression of coronary artery disease or myocardial infarction, is the critical biologic event in the pathophysiology of atherothrombosis that leads to morbidity and mortality. Trials with endpoints of myocardial infarction and death provide direct information on the effect of intervention on morbidity and mortality, but these trials require extremely large sample sizes and long duration. To obtain clinical information more quickly and with fewer patients, investigators have conducted trials using surrogate endpoints that examine the effect of treatment on the underlying disease process through measures of atherosclerotic lesion progression and/or regression and new lesion development. Coronary angiography studies have consistently shown that lipid-modifying therapy decreases coronary artery disease progression. The correlation between rate of progression of coronary artery disease and clinical coronary events such as myocardial infarction and coronary death may be explained by the relation of both to the biologic process of plaque rupture and thrombosis.