Key result
Initial invasive strategy shows no benefit over conservative therapy for 4-year CV death.
Why the study?
The ISCHEMIA trial showed no overall difference in all-cause mortality or cardiovascular death/myocardial infarction between initial invasive and conservative strategies, but detailed cause-specific death analyses had not been reported.
Does an initial invasive strategy compared with an initial conservative strategy affect cause-specific cardiovascular and non-cardiovascular mortality in patients with chronic coronary disease and moderate or severe ischemia?
RCT (n=5,179)
Open-label with blinded Clinical Events Committee adjudication
Randomly assigned to initial invasive or conservative strategy
Yes
Does an initial invasive strategy compared with an initial conservative strategy affect cause-specific cardiovascular and non-cardiovascular mortality in patients with chronic coronary disease and moderate or severe ischemia?
In the ISCHEMIA trial, all-cause and cause-specific cardiovascular mortality were low and similar between invasive and conservative strategies at 4 years, while an unexplained excess of malignancy deaths and fewer undetermined deaths occurred in the invasive arm.
Answers are grounded in this paper and cite their sources.
Similar cardiovascular mortality with invasive versus conservative strategy in chronic coronary disease; confirms neutral effect on cause-specific death and supports medical therapy first.
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
No takes yet. Share an insight, caveat, or question.
Sidhu et al. (2022) conducted an RCT in Chronic coronary disease with moderate or severe myocardial ischemia (n=5,179). Initial invasive strategy (cardiac catheterization, coronary angiography, and revascularization if feasible, plus guideline-directed medical therapy) vs. Conservative strategy with guideline-directed medical therapy alone (catheterization reserved for medical therapy failure or suspected clinical event) was evaluated on Cause-specific cardiovascular death at 4 years (HR 0.98, 95% CI 0.70 – 1.38). An initial invasive strategy resulted in similar 4-year cause-specific cardiovascular death rates compared to a conservative strategy (2.6% vs 3.0%; HR 0.98, 95% CI 0.70-1.38).
Synapse has enriched 10 related papers. Consider them for comparative context: