The CABG or PCI in Patients With Ischemic Cardiomyopathy (STICH) 3.0 International Trial Consortium

1. Study rationale The evidence from observational studies comparing long-term outcomes between percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and medical therapy in patients with iLVSD is inconsistent and likely affected by selection bias, with lower risk patients being accepted for CABG than PCI. In a large observational study including 4,794 propensity-matched patients with a LVEF <35% and CAD involving either the left anterior descending artery or multiple vessels, PCI was associated with a significantly higher risk of long-term mortality and of major adverse cardiovascular events (MACE) compared with CABG, but the risk of stroke was lower with PCI. A network meta-analysis from 2020 comparing CABG, PCI, and medical therapy (23 studies, 23,633 patients) suggested that CABG was the preferred strategy, with a reduced risk of mortality, cardiac death, MI, and urgent repeat revascularization (RR) compared to both medical therapy and PCI. A population level cohort study from Sweden including 2,509 patients from 2000-2018 with a left ventricular ejection fraction <50% also reported a significantly lower risk of death with CABG vs. PCI (odds ratio 0.62; 95%CI 0.41-0.96, p= 0.03).

There is currently a lack of evidence from randomized trials powered to compare all-cause mortality between contemporary state-of-the-art PCI vs. CABG in patients with multivessel CAD and iLVSD. Given the current clinical equipoise between both revascularization modalities in this high-risk population, a definitive answer is critically required to guide clinical practice.

The International STICH 3.0 International Trial Consortium has been established to address this ongoing conundrum in the STICH 3.0 International Collaborative Study. 2. Study objective The primary objective of the STICH 3.0 Study is to determine whether CABG is superior to PCI in terms of all-cause mortality at 7 years in patients with severe CAD and iLVSD. 3. Study design The STICH 3.0 study is composed of several individual national trials that were all prospectively designed by a multi-national steering committee to be combined in an international prospective individual patient data meta-analysis powered to examine whether CABG compared to PCI reduces the risk of death in patients with iLVSD. Individual patient data from these national RCTs, which are independently powered for different composite efficacy endpoints, will be pooled to compare mortality risk with PCI vs. CABG in patients with iLVSD. Each national study will be powered for a specific primary composite endpoint and all will collect all-cause mortality as a secondary endpoint. Harmonizing the study design elements across the national trials will enable data pooling to compare both revascularization modalities in terms of mortality with enough power. Patients with similar inclusion and exclusion criteria across trials will be merged in a large dataset powered for the objective of the international STICH 3.0 study.

3.1 National RCTs involved in the STICH 3.0 study Sweden: The primary objective is to determine whether PCI is non-inferior to CABG for revascularization in 470 patients with ischemic heart failure and LVEF≤40 in terms of the composite of death, stroke, non-procedural myocardial infarction or heart failure hospitalization at 3 years.

Canada: The primary objective is to determine whether CABG compared to PCI is superior in reducing all-cause death, stroke, spontaneous myocardial infarction (MI), urgent repeat revascularization (RR), or heart failure (HF) readmission over a median follow-up of 5 years in 754 patients with multivessel/LM CAD and iLVSD.