Randomized Controlled Trial

. 2025 Apr 26;405(10488):1481-1490.

doi: 10.1016/S0140-6736(25)00505-7. Epub 2025 Mar 30.

Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial

William F Fearon¹, Frederik M Zimmermann², Victoria Y Ding³, Kuniaki Takahashi⁴, Zsolt Piroth⁵, Albert H M van Straten⁶, Laszlo Szekely⁵, Giedrius Davidavičius⁷, Gintaras Kalinauskas⁷, Samer Mansour⁸, Rajesh Kharbanda⁹, Nikolaos Östlund-Papadogeorgos¹⁰, Adel Aminian¹¹, Keith G Oldroyd¹², Nawwar Al-Attar¹², Nikola Jagic¹³, Jan-Henk E Dambrink¹⁴, Petr Kala¹⁵, Oskar Angerås¹⁶, Philip MacCarthy¹⁷, Olaf Wendler¹⁸, Filip Casselman¹⁹, Nils Witt²⁰, Kreton Mavromatis²¹, Steven E S Miner²², Jaydeep Sarma²³, Thomas Engstrøm²⁴, Evald H Christiansen²⁵, Pim A L Tonino⁶, Michael J Reardon²⁶, Hisao Otsuki⁴, Yuhei Kobayashi²⁷, Mark A Hlatky²⁸, Kenneth W Mahaffey²⁹, Manisha Desai³, Y Joseph Woo³⁰, Alan C Yeung³¹, Nico H J Pijls⁶, Bernard De Bruyne³²

Affiliations

¹ 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. Electronic address: wfearon@stanford.edu.
² St Antonius Hospital, Nieuwegein, Netherlands; Catharina Hospital, Eindhoven, Netherlands.
³ Quantitative Sciences Unit, Stanford University, Stanford, CA, USA.
⁴ Department of Medicine, Stanford University, Stanford, CA, USA.
⁵ Gottsegen National Cardiovascular Center, Budapest, Hungary.
⁶ Catharina Hospital, Eindhoven, Netherlands.
⁷ Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania; Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.
⁸ Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
⁹ Oxford University Hospital NHS Trust, Oxford, UK.
¹⁰ Danderyd University Hospital and Karolinska Institutet, Solna, Sweden.
¹¹ Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
¹² Golden Jubilee National Hospital, Glasgow, UK.
¹³ Clinical Hospital Centre Zemun, University of Belgrade, Belgrade, Serbia.
¹⁴ Isala Hospital, Zwolle, Netherlands.
¹⁵ Medical Faculty of Masaryk University, Brno, Czech Republic; University Hospital Brno, Brno, Czech Republic.
¹⁶ Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁷ Kings College Hospital, London, UK.
¹⁸ Cleveland Clinic London, London, UK.
¹⁹ Cardiovascular Center Aalst, Aalst, Belgium.
²⁰ Södersjukhuset Hospital, Stockholm, Sweden; Karolinska Institutet, Solna, Sweden.
²¹ Atlanta VA Healthcare System, Decatur, GA, USA; Emory University School of Medicine, Atlanta, GA, USA.
²² Southlake Regional Health Centre, Newmarket, ON, Canada.
²³ Wythenshawe Hospital, Manchester, UK.
²⁴ Rigshospitalet, Copenhagen, Denmark.
²⁵ Aarhus University Hospital, Aarhus, Denmark.
²⁶ Houston Methodist Hospital, Houston, TX, USA.
²⁷ NY Presbyterian Brooklyn Methodist Hospital, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
²⁸ Department of Health Policy, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
²⁹ Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, CA, USA.
³⁰ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
³¹ Department of Medicine, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
³² Cardiovascular Center Aalst, Aalst, Belgium; Lausanne University Centre Hospital, Lausanne, Switzerland.

PMID: 40174598
DOI: 10.1016/S0140-6736(25)00505-7

Randomized Controlled Trial

Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial

William F Fearon et al. Lancet. 2025.

. 2025 Apr 26;405(10488):1481-1490.

doi: 10.1016/S0140-6736(25)00505-7. Epub 2025 Mar 30.

Authors

Affiliations

¹ 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. Electronic address: wfearon@stanford.edu.
² St Antonius Hospital, Nieuwegein, Netherlands; Catharina Hospital, Eindhoven, Netherlands.
³ Quantitative Sciences Unit, Stanford University, Stanford, CA, USA.
⁴ Department of Medicine, Stanford University, Stanford, CA, USA.
⁵ Gottsegen National Cardiovascular Center, Budapest, Hungary.
⁶ Catharina Hospital, Eindhoven, Netherlands.
⁷ Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania; Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.
⁸ Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
⁹ Oxford University Hospital NHS Trust, Oxford, UK.
¹⁰ Danderyd University Hospital and Karolinska Institutet, Solna, Sweden.
¹¹ Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
¹² Golden Jubilee National Hospital, Glasgow, UK.
¹³ Clinical Hospital Centre Zemun, University of Belgrade, Belgrade, Serbia.
¹⁴ Isala Hospital, Zwolle, Netherlands.
¹⁵ Medical Faculty of Masaryk University, Brno, Czech Republic; University Hospital Brno, Brno, Czech Republic.
¹⁶ Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁷ Kings College Hospital, London, UK.
¹⁸ Cleveland Clinic London, London, UK.
¹⁹ Cardiovascular Center Aalst, Aalst, Belgium.
²⁰ Södersjukhuset Hospital, Stockholm, Sweden; Karolinska Institutet, Solna, Sweden.
²¹ Atlanta VA Healthcare System, Decatur, GA, USA; Emory University School of Medicine, Atlanta, GA, USA.
²² Southlake Regional Health Centre, Newmarket, ON, Canada.
²³ Wythenshawe Hospital, Manchester, UK.
²⁴ Rigshospitalet, Copenhagen, Denmark.
²⁵ Aarhus University Hospital, Aarhus, Denmark.
²⁶ Houston Methodist Hospital, Houston, TX, USA.
²⁷ NY Presbyterian Brooklyn Methodist Hospital, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
²⁸ Department of Health Policy, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
²⁹ Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, CA, USA.
³⁰ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
³¹ Department of Medicine, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
³² Cardiovascular Center Aalst, Aalst, Belgium; Lausanne University Centre Hospital, Lausanne, Switzerland.

PMID: 40174598
DOI: 10.1016/S0140-6736(25)00505-7

Abstract

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.

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Conflict of interest statement

Declaration of interests WFF reports research funding from Abbott, Medtronic, and CathWorks; and has stock options with HeartFlow. SM reports consulting relationships with Abbott Vascular, Amgen, Bayer, Boehringer Ingelheim, and Novartis; and a research grant from Boehringer Ingelheim and Abbott Vascular. PK reports a consulting relationship with Boston Scientific, Medtronic, and Servier Affaires Medicales; and honoraria from AstraZeneca and Bayer. OA reports research funding from Abbott Vascular and AstraZeneca; and a consulting relationship with Abbott Vascular and Boston Scientific. SM reports a consulting relationship with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Opsens, Pfizer, and Servier Affaires Medicales. TE reports a consulting relationship with Abbott Vascular, Bayer, and Novo Nordisk. EHC reports a consulting relationship with Abbott Vascular; and research grants from Abbott Vascular. PALT reports receiving research grants from Biosensors and Opsens. MJR reports a consulting relationship with Medtronic, Abbott, Boston Scientific, Gore Medical, Anteris, and JC Medical. HO reports receiving research grants from the Uehara Memorial Foundation, Abbott, Medtronic, Boston Scientific, and Terumo. YK reports institutional research support from CathWorks; and a research agreement with Medis. MAH reports a consulting relationship with Blue Cross and Blue Shield; and research support from HeartFlow. KWM reports research grants or contracts from the American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, Eidos, Ferring, Gilead, Google (Verily), Idorsia, Johnson & Johnson, Luitpold, PAC-12, Precordior, and Sanifit; has provided consulting or other services for Amgen, Applied Therapeutics, AstraZeneca, Bayer, CSL Behring, Elsevier, FibroGen, Inova, Johnson & Johnson, Lexicon, MyoKardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, Sanofi, and Theravance; and has equity in Precordior. ACY reports a consulting relationship with Medtronic. NHJP reports research funding from Abbott; consulting relationships with Abbott and Opsens; and stock with ASML, General Electric, HeartFlow, Hexacath, and Philips. BDB reports an institutional consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and minor equities in Philips, Siemens, GE Healthcare, CathWorks, Edwards Life Sciences, HeartFlow, Opsens, Celyad, Xenter, Medyria, Bayer, and Sanofi. All other authors declare no competing interests.

Comment in

Fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting: please mind the gap.
Tam DY, Lee G, Chikwe J. Tam DY, et al. Lancet. 2025 Apr 26;405(10488):1441-1443. doi: 10.1016/S0140-6736(25)00583-5. Epub 2025 Mar 30. Lancet. 2025. PMID: 40174595 No abstract available.

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Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial

Affiliations

Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

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Medical

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