Assessment of Nonfatal Myocardial Infarction as a Surrogate for All-Cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease

Abstract

IMPORTANCEAlthough nonfatal myocardial infarction (MI) is associated with an increased risk of mortality, evidence validating nonfatal MI as a surrogate end point for all-cause or cardiovascular (CV) mortality is lacking.OBJECTIVE To examine whether nonfatal MI may be a surrogate for all-cause or CV mortality in patients with or at risk for coronary artery disease.DATA SOURCES In this meta-analysis, PubMed was searched from inception until December 31, 2020, for randomized clinical trials of interventions to treat or prevent coronary artery disease reporting mortality and nonfatal MI published in 3 leading journals.STUDY SELECTION Randomized clinical trials including at least 1000 patients with 24 months of follow-up. DATA EXTRACTION AND SYNTHESISTrial-level correlations between nonfatal MI and all-cause or CV mortality were assessed for surrogacy using the coefficient of determination (R 2 ). The criterion for surrogacy was set at 0.8. Subgroup analyses based on study subject (primary prevention, secondary prevention, mixed primary and secondary prevention, and revascularization), era of trial (before 2000, 2000-2009, and 2010 and after), and follow-up duration (2.0-3.9, 4.0-5.9, and Ն6.0 years) were performed. MAIN OUTCOMES AND MEASURES All-cause or CV mortality and nonfatal MI.RESULTS A total of 144 articles randomizing 1 211 897 patients met the criteria for inclusion. Nonfatal MI did not meet the threshold for surrogacy for all-cause (R 2 = 0.02; 95% CI, 0.00-0.08) or CV (R 2 = 0.11; 95% CI, 0.02-0.27) mortality. Nonfatal MI was not a surrogate for all-cause mortality in primary (R 2 = 0.01; 95% CI, 0.001-0.26), secondary (R 2 = 0.03; 95% CI, 0.00-0.20), mixed primary and secondary prevention (R 2 = 0.001; 95% CI, 0.00-0.08), or revascularization trials (R 2 = 0.21; 95% CI, 0.002-0.50). For trials enrolling patients before 2000 (R 2 = 0.22; 95% CI, 0.08-0.36), between 2000 and 2009 (R 2 = 0.02; 95% CI, 0.00-0.17), and from 2010 and after (R 2 = 0.01; 95% CI, 0.00-0.09), nonfatal MI was not a surrogate for all-cause mortality. Nonfatal MI was not a surrogate for all-cause mortality in randomized clinical trials with 2.0 to 3.9 (R 2 = 0.004; 95% CI, 0.00-0.08), 4.0 to 5.9

Prediction of risk for bleeding, myocardial infarction and mortality after percutaneous coronary intervention in patients with acute coronary syndromes

“…Thus, as in the case of bleeding, the occurrence of MI appears to be a marker of worse cardiovascular risk profile which may be an underlying factor for increased risk for mortality. A recent large meta-analysis of randomized clinical trials of interventions to treat coronary artery disease suggested that nonfatal MI appears not to be a surrogate for all-cause or cardiovascular mortality [25]. Second, in the current study, MI included spontaneously occurring (type 1) and periprocedural MI based on the measurements of high-sensitivity cardiac troponins.…”

Non-fatal MI is not a surrogate for cardiovascular or all-cause mortality

“…The authors of a meta-analysis assessed trial data spanning 50 years and concluded that non-fatal myocardial infarction is not a robust surrogate outcome for mortality 1…”

“…This meta-analysis of clinical trial data assessed whether non-fatal myocardial infarction (MI) is a robust surrogate outcome for all-cause or cardiovascular mortality in people with, or at risk of, coronary artery disease 1. The authors searched for randomised controlled trials (RCTs) of interventions to treat or prevent coronary artery disease published in three journals ( The New England Journal of Medicine, Journal of the American Medical Association or The Lancet ).…”

“…In a pooled analysis of 144 RCTs, assignment to the intervention arm reduced the rate of non-fatal MI from 4.2% to 3.7% (OR 0.87; 95% CI 0.85 to 0.90; p<0.001) and reduced all-cause mortality from 7.3% to 7.0% (OR 0.95; 95% CI 0.93 to 0.97; p<0.001) 1. To assess the association between non-fatal MI and mortality, the authors plotted log-transformed ORs or hazard ratios for non-fatal MI against those for cardiovascular or all-cause mortality.…”

Temporal trends in the efficacy of revascularization in stable ischaemic heart disease: A cumulative meta-analysis

“…The latter may be explained by the improved management of spontaneous MIs, which results in reduced fatality rates than several decades ago. Also, a recent meta-regression analysis of large coronary artery disease trials showed that non-fatal MI is a poor surrogate outcome for all-cause or cardiovascular mortality [6] . We have to note as well that spontaneous MI was not a pre-specified endpoint of any of the eligible trials.…”