Fractional Flow Reserve–Guided Complete vs Culprit-Only Revascularization in Non–ST-Elevation Myocardial Infarction and Multivessel Disease

The benefits of fractional flow reserve (FFR)-guided complete coronary revascularization in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and multivessel disease remain unclear. To compare FFR-guided complete revascularization of nonculprit lesions vs culprit-only revascularization in patients with NSTEMI and multivessel disease. This prospective, investigator-initiated, multicenter, international randomized clinical trial was conducted at 9 hospitals in Europe. Patients with NSTEMI and multivessel disease who had successful revascularization of the culprit lesion were enrolled between June 2018 and July 2024, and final follow-up was completed on July 21, 2025. The analysis was conducted on July 28, 2025. Eligibility criteria included the presence of at least 1 stenosis of at least 50% in a nonculprit lesion amendable for revascularization. Patients were randomized to receive either FFR-guided complete or culprit-only revascularization during the index procedure. Staged revascularization within 6 weeks after the index procedure was allowed in the culprit-only group. The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, any revascularization, and stroke at 1 year. Key secondary outcomes included individual components of the primary outcome, net adverse clinical events, all-cause death or nonfatal myocardial infarction, cardiac rehospitalization, and bleeding events. Among 478 randomized patients (mean SD age, 65.9 10.6 years; 347 72.9% males), 240 were randomized to receive FFR-guided complete revascularization and 238 were randomized to receive culprit-only revascularization, with crossover occurring in 7 patients in the culprit-only group. The primary outcome occurred in 13 patients (5.5%) in the FFR-guided complete revascularization group vs 32 patients (13.6%) in the culprit-only group (hazard ratio HR, 0.38 95% CI, 0.20-0.72; P = .003). Rates of any revascularization (3.0% vs 11.5%; HR, 0.24 95% CI, 0.11-0.56; P < .001) and net adverse clinical events (6.3% vs 15.3%; HR, 0.39 95% CI, 0.21-0.70; P = .002) were also significantly lower in the complete revascularization group, while there were no significant differences in the remaining secondary outcomes. FFR-guided complete revascularization during the index procedure resulted in a significant reduction in the composite of all-cause death, nonfatal myocardial infarction, any revascularization, and stroke at 1 year. This was mainly driven by reduced repeat revascularization. ClinicalTrials.gov Identifier: NCT03562572.