BACKGROUND: Long-term outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) might be changing because of improved techniques and better medical therapy. This final prespecified analysis of the Fractional Flow Reserve (FFR) versus Angiography for Multivessel Evaluation (FAME) 3 trial aimed to reassess their comparative effectiveness at 5 years. METHODS: FAME 3 was a multicentre, randomised trial comparing FFR-guided PCI using current-generation zotarolimus-eluting stents versus CABG in patients with three-vessel coronary artery disease not involving the left main coronary artery. 48 hospitals in Europe, USA and Canada, Australia, and Asia participated in the trial. Patients (aged ≥21 years with no cardiogenic shock, no recent ST segment elevation myocardial infarction, no severe left ventricular dysfunction, and no previous CABG) were randomly assigned to either PCI or CABG using a web-based system. At 1 year, FFR-guided PCI did not meet the prespecified threshold for non-inferiority for the outcome of death, stroke, myocardial infarction, or repeat revascularisation versus CABG. The primary endpoint for this intention-to-treat analysis was the 5-year incidence of the prespecified composite outcome of death, stroke, or myocardial infarction. The trial was registered at ClinicalTrials.gov, NCT02100722, and is completed; this is the final report. FINDINGS: Between Aug 25, 2014 and Nov 28, 2019, 757 of 1500 participants were assigned to PCI and 743 to CABG. 5-year follow-up was achieved in 724 (96%) patients assigned to PCI and 696 (94%) assigned to CABG. At 5 years, there was no significant difference in the composite of death, stroke, or myocardial infarction between the two groups, with 119 (16%) events in the PCI group and 101 (14%) in the CABG group (hazard ratio 1·16 [95% CI 0·89-1·52]; p=0·27). There were no differences in the rates of death (53 [7%] vs 51 [7%]; 0·99 [0·67-1·46]) or stroke (14 [2%] vs 21 [3%], 0·65 [0·33-1·28]), but myocardial infarction was higher in the PCI group than in the CABG group (60 [8%] vs 38 [5%], 1·57 [1·04-2·36]), as was repeat revascularisation (112 [16%] vs 55 [8%], 2·02 [1·46-2·79]). INTERPRETATION: At the 5-year follow-up, there was no significant difference in a composite outcome of death, stroke, or myocardial infarction after FFR-guided PCI versus CABG, although myocardial infarction and repeat revascularisation were higher with PCI. These results provide contemporary evidence to allow improved shared decision making between physicians and patients. FUNDING: Medtronic and Abbott Vascular.

Aarhus University Hospital Aarhus Denmark

Atlanta VA Healthcare System Decatur GA USA; Emory University School of Medicine Atlanta GA USA

Cardiovascular Center Aalst Aalst Belgium

Cardiovascular Center Aalst Aalst Belgium; Lausanne University Centre Hospital Lausanne Switzerland

Catharina Hospital Eindhoven Netherlands

Centre Hospitalier de l'Université de Montréal Montreal QC Canada

Centre Hospitalier Universitaire de Charleroi Charleroi Belgium

Cleveland Clinic London London UK

Clinic of Cardiac and Vascular Diseases Institute of Clinical Medicine Vilnius University Vilnius Lithuania; Vilnius University Hospital Santaros Klinikos Vilnius Lithuania

Clinical Hospital Centre Zemun University of Belgrade Belgrade Serbia

Danderyd University Hospital and Karolinska Institutet Solna Sweden

Department of Cardiothoracic Surgery Stanford University Stanford CA USA

Department of Health Policy Stanford University Stanford CA USA; Department of Medicine Stanford University Stanford CA USA

Department of Medicine Stanford University Stanford CA USA

Department of Medicine Stanford University Stanford CA USA; Stanford Cardiovascular Institute Stanford University Stanford CA USA

Department of Medicine Stanford University Stanford CA USA; Stanford Cardiovascular Institute Stanford University Stanford CA USA; VA Palo Alto Health Care System Palo Alto CA USA

Golden Jubilee National Hospital Glasgow UK

Gottsegen National Cardiovascular Center Budapest Hungary

Houston Methodist Hospital Houston TX USA

Isala Hospital Zwolle Netherlands

Kings College Hospital London UK

Medical Faculty of Masaryk University Brno Czech Republic; University Hospital Brno Brno Czech Republic

NY Presbyterian Brooklyn Methodist Hospital New York NY USA; Weill Cornell Medical College New York NY USA

Oxford University Hospital NHS Trust Oxford UK

Quantitative Sciences Unit Stanford University Stanford CA USA

Rigshospitalet Copenhagen Denmark

Sahlgrenska University Hospital Gothenburg Sweden

Södersjukhuset Hospital Stockholm Sweden; Karolinska Institutet Solna Sweden

Southlake Regional Health Centre Newmarket ON Canada

St Antonius Hospital Nieuwegein Netherlands; Catharina Hospital Eindhoven Netherlands

Stanford Center for Clinical Research Department of Medicine Stanford University Stanford CA USA

Wythenshawe Hospital Manchester UK

Lancet. 2025 Apr 26;405(10488):1441-1443. doi: 10.1016/S0140-6736(25)00583-5. PubMed

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ClinicalTrials.gov
NCT02100722