IMPORTANCE: Outcomes in patients with diabetes after fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) using current-generation drug-eluting stents (DES) compared with coronary artery bypass grafting (CABG) are unknown. OBJECTIVES: To investigate the relative treatment effect of PCI vs CABG according to diabetes status with respect to major adverse cardiac and cerebrovascular events (MACCE) at 3 years and to evaluate the impact of the SYNTAX score. DESIGN, SETTING, AND PARTICIPANTS: This is a prespecified subgroup analysis of the FAME (Fractional Flow Reserve vs Angiography for Multivessel Evaluation) 3 trial, an investigator-initiated, randomized clinical trial conducted at 48 centers worldwide. The FAME 3 trial enrolled patients with 3-vessel coronary artery disease not involving the left main undergoing coronary revascularization between August 2014 and December 2019. Data analysis was conducted in August 2023. Clinical follow-up was performed at hospital discharge and at 1 month, 6 months, 1 year, 2 years, and 3 years after randomization. INTERVENTION: Either FFR-guided PCI with current-generation DES or CABG. MAIN OUTCOMES AND MEASURES: The primary end point was MACCE, defined as the composite of all-cause death, myocardial infarction, stroke, or repeat revascularization at 3 years. RESULTS: Of 1500 total patients enrolled, mean (SD) patient age was 65.1 (8.4) years, and 265 patients (17.7%) were female. The FAME 3 trial included 428 patients with diabetes (28.5%). Patients with diabetes, especially those receiving insulin, had a higher risk of MACCE at 3 years compared with those without diabetes. Regarding relative treatment effect, the risk of MACCE was higher after FFR-guided PCI compared with CABG in both patients with diabetes (hazard ratio [HR], 1.44
95% CI, 0.91-2.28
P = .12) and those without diabetes (HR, 1.50
95% CI, 1.08-2.07
P = .02), with no significant interaction (P for interaction = .94). In patients with a low SYNTAX score (<
23), there was no significant difference in MACCE between PCI and CABG, while in patients with an intermediate to high SYNTAX score (≥23), PCI had a higher risk of MACCE than CABG, regardless of diabetes status. CONCLUSIONS AND RELEVANCE: In this subgroup analysis of the FAME 3 randomized clinical trial, the relative benefit of CABG compared with FFR-guided PCI was similar among patients with and without diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02100722.