Nonfatal Myocardial Infarction—Poor Surrogate for Mortality

Advances in the treatment and prevention of coronary artery disease (CAD) have been associated with decreases in mortality rates. Thus, researchers have begun to incorporate nonfatal myocardial infarction (MI) into composite outcomes to enable adequately powered yet feasibly sized clinical trials. Nonfatal MI is an important end point to patients—patients want to avoid the experience of an(other) MI, but this end point is also often targeted based on the belief that preventing subsequent MIs can lead to lower cardiovascular mortality.¹ While it is biologically plausible for nonfatal MI to predict mortality, there is little evidence to show that it actually does. In this issue of JAMA Internal Medicine, O'Fee et al² evaluate the appropriateness of nonfatal MI as a surrogate measure to predict mortality. This meta-analysis of 144 randomized clinical trials involving 1 211 897 patients reported that nonfatal MI did not meet the threshold for surrogacy for either all-cause mortality (R² = 0.02; 95% CI 0.00-0.08) or cardiovascular mortality (R² = 0.11; 95% CI 0.02-0.27). The results were consistent across primary prevention, secondary prevention, and revascularization trials.²