Causes of Cardiovascular and Non-Cardiovascular Death in the ISCHEMIA Trial. American heart journal Sidhu, M. S., Alexander, K. P., Huang, Z., O'Brien, S. M., Chaitman, B. R., Stone, G. W., Newman, J. D., Boden, W. E., Maggioni, A. P., Steg, P. G., Ferguson, T. B., Demkow, M., Peteiro, J., Wander, G. S., Phaneuf, D. C., De Belder, M. A., Doerr, R., Alexanderson-Rosas, E., Polanczyk, C. A., Henriksen, P. A., Conway, D. S., Miro, V., Sharir, T., Lopes, R. D., Min, J. K., Berman, D. S., Rockhold, F. W., Balter, S., Borrego, D., Rosenberg, Y. D., Bangalore, S., Reynolds, H. R., Hochman, J. S., Maron, D. J. 2022


The ISCHEMIA trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported.We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as cardiovascular (CV), non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death.Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies [2.6% vs. 3.0%; hazard ratio (HR) 0.98; 95% CI (0.70 - 1.38)], but non-CV death rates were higher in the invasive strategy [3.3% vs. 2.1%; HR 1.45 (1.00 - 2.09)]. Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths [0.6% vs. 1.3%; HR 0.48 (0.24 - 0.95)] and more malignancy deaths [2.0% vs. 0.8%; HR 2.11 (1.23 - 3.60)] occurred in the invasive strategy than in the conservative strategy.In ISCHEMIA, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.

View details for DOI 10.1016/j.ahj.2022.01.017

View details for PubMedID 35149037