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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 April 1, 2025 e813

ing occurs as a single procedure as opposed to when staged.10–12 The decision to proceed with multivessel stenting and the timing of the procedure should take into account the patient’s clinical and hemodynamic status, the duration and complexity of the infarct-related artery PCI, the complexity of disease in the noninfarct-related artery, the amount of myocardium in jeopardy, and the presence of comorbidities that might favor a conservative approach to care. Few studies of multivessel PCI have directly compared the efficacy of a physiologic-guided PCI versus an angiographic-guided PCI approach.17,18 A meta-analysis across trials did not suggest any differential benefit for complete revascularization based on whether the approach was guided by fractional flow reserve (FFR) or angiography alone.3

Recommendation-Specific Supportive Text

1 Over the past decade, numerous trials have reported

a significant reduction in MACE with complete revascularization.1,2,4–8 These studies have demonstrated benefits to complete revascularization either at the time of PPCI2,5–8 or as a staged procedure.1,2,4,6 The PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) trial,8 one of the earliest trials of multivessel PCI, randomized 465 patients with STEMI and MVD to a strategy of complete revascularization versus culprit artery only revascularization. The trial was stopped early due to a significant reduction in the primary composite endpoint (cardiovascular death, nonfatal MI, or refractory angina) with complete revascularization, with significant reductions in nonfatal MI and refractory angina and a trend in reduction in the rates of cardiovascular death. The COMPLETE (Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial1 randomized 4041 patients with STEMI and significant MVD to a strategy of staged PCI of the non–infarct-related artery (performed up to 45 days post MI) or culprit vessel–only revascularization with PCI reserved for patients with refractory symptoms. At a median follow-up of 3 years, multivessel PCI reduced cardiovascular death or MI and cardiovascular death, MI, or ischemia-driven revascularization. This benefit was consistent across all subgroups. Angina-related QOL was also significantly improved with multivessel PCI, with a greater proportion of patients in the complete revascularization arm who were anginafree in long-term follow-up.9 In a meta-analysis, complete revascularization reduced cardiovascular death in patients with STEMI.19 The benefits of complete revascularization with multivessel PCI should not be extrapolated to patients with disease more suited to CABG surgery, because they were excluded from these trials. 2 The trials examining the benefit of multivessel

PCI in patients with STEMI and MVD excluded patients intended for CABG surgery. Furthermore, few patients with complex disease, such as chronic total occlusions or involvement of the left main artery, were included in these trials. For this reason, the benefits of a strategy of multivessel PCI cannot be extrapolated to patients with more complex noninfarct-related artery disease. In patients with CCD and complex CAD, including complex left main disease, or in patients with diabetes who have MVD involving the left anterior descending artery, CABG surgery is associated with improved event-free survival when compared with PCI.20–24 As such, a similar benefit of CABG over PCI might be expected for patients with STEMI and complex non–infarct-related artery disease involving the left main or left anterior descending artery or in patients with diabetes and MVD involving the left anterior descending artery, who are stable and remote from their acute infarct, although the optimal timing of CABG is unclear in this setting and needs to take into account increased bleeding risk from DAPT. 3.	 Performing multivessel PCI at the time of PPCI

offers the convenience of a single procedure, allowing for faster recovery, without the risk of repeated arterial access, or the potential for recurrent ischemia before the staged PCI. The BIOVASC (Direct Complete Versus Staged Complete Revascularization in Patients Presenting With Acute Coronary Syndromes and Multivessel Disease) trial10 randomized 1525 patients with ACS (∼40% with STEMI) and MVD to a strategy of a single setting immediate multivessel PCI or staged multivessel PCI. At 1 year, immediate multivessel PCI was noninferior to staged multivessel PCI for the primary endpoint all-cause death, MI, unplanned ischemia-driven revascularization, or cerebrovascular events. When compared with staged PCI, a single procedure multivessel PCI was associated with lower rates of recurrent MI and lower rates of unplanned ischemia-driven revascularization. The MULTISTARS AMI (Multivessel Immediate Versus Staged Revascularization in Acute Myocardial Infarction) study11 compared a strategy of a single procedure multivessel PCI with staged multivessel PCI in 840 patients with STEMI and MVD. Immediate multivessel PCI was noninferior and superior to staged multivessel PCI for the primary endpoint of death, reinfarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for HF at 1 year. This was largely driven by a lower rate of recurrent ischemia and recurrent infarction in the immediate group. In a network meta-analysis comparing all strategies for managing the non–infarct-related artery, a single

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