Optimal Timing of Staged Complete Revascularization in STEMI With Multivessel Disease

Overview

This prospective, multicenter, open-label, superiority trial will enroll patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. Following successful percutaneous coronary intervention (PCI) of the infarct-related artery (IRA), patients who meet the eligibility criteria will be randomized in a 1:1 ratio to either in-hospital staged complete revascularization with PCI of non-IRA lesions performed on a separate day during hospitalization, at least 48 hours after PCI of the IRA, or out-of-hospital staged complete revascularization with PCI of non-IRA lesions performed after discharge between 15 and 45 days of randomization. In both groups, non-IRA lesions with 50-69% stenosis will be evaluated using FFR.

* Study Objectives: To determine the optimal timing of staged complete revascularization guided by fractional flow reserve (FFR) (in-hospital staged complete revascularization vs. out-of-hospital staged complete revascularization) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. * Study Background: Approximately half of patients with STEMI have multivessel coronary artery disease, which is associated with worse clinical outcomes than single vessel disease. Complete revascularization has become the standard interventional strategy for the management of these patients. Regarding the timing of complete revascularization, two recent randomized clinical trials demonstrated that immediate complete revascularization was non-inferior to staged complete revascularization in patients with STEMI. In this context, the 2023 European guidelines give a class IA recommendation for complete revascularization, either during the index procedure or within 45 days. The 2025 American guidelines recommend immediate complete revascularization with a class IIb recommendation for hemodynamically stable patients with STEMI and low-complex anatomy. However, in these trials, planned staged revascularization in the staged group was performed after hospital discharge rather than during the index admission. In those previous trials, the timing of staged revascularization was median 15 days (IQR 4-28) in the BIOVASC trial and median 37 days (IQR 30-43) in the MULTISTARS AMI trial, and most clinical events in the staged group (mainly due to unplanned revascularization and myocardial infarction) had occurred during the early phase after the index procedure with the possibility of progression of a non-infarct related artery (non-IRA) lesion before the staged procedure. Greater inflammatory status during the acute phase of myocardial infarction might be associated with these findings. The OPTION-STEMI trial, which compared immediate and staged complete revascularization during index hospitalization, failed to demonstrate non-inferiority for the primary endpoint at 1 year (13% in the immediate complete revascularization group and 11% in the staged complete revascularization group; hazard ratio 1.24; 95% confidence interval 0.86-1.79; P for non-inferiority = 0.024). Therefore, it remains unclear whether the treatment effect differs between in-hospital and out-of-hospital staged complete revascularization in patients with STEMI and multivessel disease. The investigators designed a prospective, open-label, multicenter, superiority trial to evaluate the efficacy and safety of in-hospital staged complete revascularization compared with out-of-hospital staged complete revascularization in patients with STEMI and multivessel disease. Non-IRA lesions with 50-69% stenosis will be assessed using FFR, whereas those with ≥ 70% stenosis will undergo revascularization without FFR assessment. The investigators hypothesize that in-hospital staged complete revascularization may mitigate the risk of early progression of non-IRA lesions, compared with out-of-hospital staged complete revascularization, without increasing the procedural risk associated with immediate complete revascularization. * Study Hypothesis: In-hospital staged complete revascularization would reduce the risk of the primary composite endpoint (a composite of all-cause death, non-fatal myocardial infarction, or all unplanned revascularization) at 12 months compared with out-of-hospital staged complete revascularization in patients with STEMI and multivessel disease.