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Editor's Note
October 25, 2021

Nonfatal Myocardial Infarction—Poor Surrogate for Mortality

Author Affiliations
  • 1Department of Medicine, University of California, San Francisco
  • 2Editorial Fellow, JAMA Internal Medicine
  • 3Duke University, Duke Clinical Research Institute, Durham, North Carolina
  • 4Associate Editor, JAMA Internal Medicine
JAMA Intern Med. 2021;181(12):1588. doi:10.1001/jamainternmed.2021.5713

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

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1 Comment for this article
Non- fatal Myocardial Infarction
Michael Plunkett, MD MBA | Teaching
Non-fatal myocardial infarction is used in studies as a marker because there are enough of these events to give the study “statistical significance.“ I teach trainees to look at the table and take the non-fatal myocardial infarctions out.  What do you have? Insignificance.

Researchers may care about non-fatal myocardial infarctions as an endpoint. Patient certainly don’t. Patients are afraid of “the big one,” and they’re right.

The only usefulness of nonfatal myocardial infarction is to let the physician know the patient has the disease, and to make sure that the patient has optimal medical therapy.