Among participants from the ISCHEMIA trial, cause-specific death rates were analyzed and findings revealed similar all-cause and cardiovascular (CV) death rates between treatment strategies. The invasive strategy was associated with fewer undetermined deaths and more malignancy deaths; this observation remains unexplained. These results need to be interpreted with caution in the context of previous studies and the overall trial findings.

• In the ISCHEMIA trial, the composite primary endpoint and the secondary endpoints of CV death/myocardial infarction or all-cause mortality did not differ overall between an initial invasive or conservative strategy among patients with chronic coronary disease and moderate or severe myocardial ischemia.

• For deaths attributable to CV conditions, the 4-year cumulative incidence rates were found to be similar between invasive and conservative strategies [2.6% vs 3.0%; hazard ratio (HR) 0.98], but non-CV death rates were higher in the invasive strategy [3.3% vs 2.1%; HR 1.45].

• Deaths due to undetermined causes (38/289) comprised 13% of the overall deaths.

• In the invasive strategy arm, fewer undetermined deaths [0.6% vs 1.3%; HR 0.48] and more malignancy deaths [2.0% vs 0.8%; HR 2.11] occurred when compared to the conservative strategy.