Initial invasive versus conservative management of stable ischemic heart disease in patients with a history of heart failure or left ventricular dysfunction

Selected in Circulation by D. Milasinovic

Insights from the ISCHEMIA Trial, commented by D. Milasinovic

Reviewer

Dejan Milasinovic

@MilasinD18

Interventional cardiologist / Cardiologist

Belgrade, Serbia

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My Comment

Why this study? – the rationale/objective

This secondary analysis of the ISCHEMIA trial sought to evaluate the impact of revascularization in patients with chronic coronary artery disease (CAD) and heart failure (HF) and/or left ventricular dysfunction (LVD, with EF 35-45%).

How was it executed? – the methodology

• Of the 5179 patients with chronic coronary disease (left main stenosis >50% excluded), 7.7% (n=398) had HF/LVD.
• The primary combined endpoint was cardiovascular death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or HF.
• Median follow-up was 3.2 years.

What is the main result?

• Presence of HF or LVD in patients with chronic coronary disease was independently associated with the increased risk of the primary endpoint, but also of all-cause and cardiovascular mortality. 
• Compared with initial conservative management, routine revascularization reduced the occurrence of the primary endpoint (17.2% vs. 29.3%) and of the combined endpoint of cardiovascular death or MI (14.6% vs. 25.9%), in patients with the history of HF or LVD at baseline.
• Interaction tests (p=0.055 for the primary endpoint; p=0.061 for CV death/MI) confirmed the tendency for baseline HF or LVD to modify the effect of revascularization in patients with chronic coronary syndromes.

Critical reading and the relevance for clinical practice

In the light of the overall ISCHEMIA trial results suggesting that routine initial revascularization in patients with chronic CAD may not confer additional benefit over optimal medical therapy (at least for the duration of median follow-up of 3 years), this secondary analysis opens a window of opportunity to improve prognosis by revascularizing patients with chronic CAD and history of HF or LVD.

There appear at least 2 issues worth considering in the interpretation of this study. First, prior MI was twice as frequent in the subgroup of patients with HF/LVD (17.7% vs. 37%), but it appears not to have been accounted for in the regression analysis. As prior MI is associated with increased risk of future ischemic events, it may be a further important modifier of the effect of revascularization in patients with chronic CAD, that could be independent from and/or synergistic with HF/LVD. Second, the here presented evidence could be put in the perspective of the STICH trial, which demonstrated a long-term (10 year) mortality benefit of CABG over medical therapy in patients with EF<35%. Thereby, it is interesting to appreciate that in the ISCHEMIA trial, revascularization was beneficial in patients with mid-range reduced EF. Also, the longer-term follow-up may bring new insights to the ISCHEMIA trial, both in patients with and without HF/LVD, especially given the continuous separation of Kaplan Meier curves for the endpoint of spontaneous MI in favour of the invasive strategy. 

Notwithstanding its hypothesis-generating nature, the here presented ISCHEMIA sub-study does seem to add further evidence to the notion that when deciding about revascularization in chronic CAD, a multitude of factors beyond the mere angiographic appearance of CAD need to be taken into consideration. In this respect, a possible approach could be creation of integrative patient risk profiles combining data from angiography, intracoronary imaging & physiology with clinical risk factors, the degree of LV impairment and the overall atherosclerosis burden.