Researchers, take note: Nonfatal MI not a surrogate for all-cause or cardiovascular mortality
Nonfatal myocardial infarction (MI) should not be used as a surrogate endpoint for all-cause or cardiovascular mortality in research related to coronary artery disease, according to new data published in JAMA Internal Medicine.
"In the early 1990s, Braunwald and colleagues suggested that combining mortality with nonfatal complications might better inform the overall outcomes of experimental therapies, accelerate the pace of evaluating proposed innovations, and minimize the number of patients exposed to ineffective therapies," wrote lead author Kevin O’Fee, MD, with the department of medicine at Washington University School of Medicine in St Louis, and colleagues. "Nonfatal MI was subsequently incorporated as an endpoint in landmark studies of acute coronary syndromes and ultimately in almost all studies of treatment or prevention of coronary artery disease based on the assumption that nonfatal MI was a surrogate for mortality and that preventing nonfatal MI would reduce mortality—a belief that endures. However, the use of nonfatal MI as a surrogate for mortality has been questioned for not meeting accepted standards for surrogacy."
To look closer at this issue, the team examined data from 144 different clinical trial, covering 1,211,897 patients.
In the analysis, it was determined that nonfatal MI “did not meet the threshold for surrogacy for all-cause or CV mortality.”
“Results of this meta-analysis suggest that treatments that reduce nonfatal myocardial infarction cannot be assumed to reduce all-cause or cardiovascular mortality,” the authors wrote.
Nonfatal MI may still be an effective endpoint, the team added, just "not based on its surrogacy for mortality."
In an accompanying editorial, Mithi del Rosario, MD, with the department of medicine at the University of California, San Francisco, and colleagues said that this study has implications for how healthcare researchers should examine their work going forward.
“Overall, this study raises important questions on the appropriateness of nonfatal MI as a clinical trial endpoint, with specific emphasis on methodologic concerns and an inability to predict mortality,” the group said.
Read the full study here. The additional editorial can be found here.