A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease

NCT02100722 | Completed Results DMC

• 1 other identifier: FAME 3
• Study Type: interventional
• Target: 1,500
• Locations: 15 countries
• Sites: 44

Brief Summary

The purpose of this study is to determine whether Fractional flow reserve (FFR, (coronary pressure wire-based index for assessing the ischemic potential of a coronary lesion)-guided percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease (CAD) will result in similar outcomes to coronary artery bypass graft surgery (CABG).

Conditions

Coronary Disease; Coronary Stenosis

Outcome Measures

Primary Outcomes (1)

• MACCE

  Death, MI, stroke and any repeat revascularization (MACCE) will be evaluated at 1 year, where subjects contribute data from time of randomization until the occurrence of MACCE or one year follow-up, whichever occurs first. Subjects who die or are lost to follow up before 1 year will be censored at their last recorded activity.

  1 year

Secondary Outcomes (15)

• Key Secondary Outcome: Composite of Death From Any Cause, Myocardial Infarction, or Stroke

  3 years

• Number of Participants Experiencing Death, MI, or Stroke

  1 year

• Death

  1 year

• Number of Participants Experiencing Myocardial Infarction

  1 year

• Number of Participants Experiencing Stroke

  1 year

Study Arms (2)

FFR guided PCI

ACTIVE COMPARATOR

Patients undergoing PCI will have FFR measured with a St. Jude Medical coronary pressure wire across all lesions. If the FFR is ≤0.80, then PCI will be performed with the Medtronic Resolute Integrity (or Onyx) drug-eluting stent (DES) as per usual routine. If the FFR is \>0.80 then PCI will be deferred. Only those sites with prior experience measuring FFR will be included in the FAME 3 trial. These patients in whom FFR of a particular lesion was not possible will be included in all analyses based on the intention to treat principle.

Procedure: FFR guided PCI; Device: Resolute Integrity Stent; Device: Resolute Onyx Stent

CABG

ACTIVE COMPARATOR

CABG will be performed as per clinical routine at each participating center. Both off-pump and on-pump surgery are acceptable, as long as the surgeon and the site are experienced in the particular technique. An internal mammary graft to the LAD should be attempted in all cases, if feasible. Complete arterial revascularization is strongly recommended, however, each center should use a conduit strategy with which they are most comfortable. All vessels ≥ 1,5 mm in diameter and with ≥ 50% stenosis should be bypassed, if technically feasible.

Procedure: CABG

Interventions

Resolute Integrity Stent DEVICE

Durable polymer zotarolimus-eluting stent

FFR guided PCI

Resolute Onyx Stent DEVICE

Durable polymer zotarolimus-eluting stent

FFR guided PCI

FFR guided PCI PROCEDURE

Also known as: Fractional Flow Reserve-Guided PCI

FFR guided PCI

CABG PROCEDURE

Coronary Artery Bypass Graft Surgery (CABG)

CABG

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥ 21 years with angina and/or evidence of myocardial ischemia
• \. Three vessel CAD, defined as ≥ 50% diameter stenosis by visual estimation in each of the three major epicardial vessels or major side branches, but not involving left main coronary artery, and amenable to revascularization by both PCI and CABG as determined by the Heart Team. Patients with a non-dominant right coronary artery may be included if only the left anterior descending artery (LAD) and left circumflex have ≥50% stenosis
• \. Willing and able to provide informed, written consent

You may not qualify if:

• \. Requirement for other cardiac or non-cardiac surgical procedure (e.g., valve replacement, carotid revascularization)
• \. Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
• \. Recent STEMI (\<5 days prior to randomization)
• \. Ongoing Non STEMI with biomarkers (cardiac troponin) still rising
• \. Known left ventricular ejection fraction \<30%
• \. Life expectancy \< 2 years
• \. Requiring renal replacement therapy
• \. Undergoing evaluation for organ transplantation
• \. Participation or planned participation in another clinical trial, except for observational registries
• \. Pregnancy
• \. Inability to take dual antiplatelet therapy for six months
• \. Previous CABG
• \. Left main disease requiring revascularization
• \. Extremely calcified or tortuous vessels precluding FFR measurement
• \. Any target lesion with in-stent drug-eluting stent restenosis

Sponsors & Collaborators

• Stanford University: lead
• Medtronic: collaborator
• VZW Cardiovascular Research Center Aalst: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Golden Jubilee National Hospital: collaborator
• University of California, Irvine: collaborator
• Abbott Medical Devices: collaborator
• Genae: collaborator
• King's College Hospital NHS Trust: collaborator
• Houston Methodist DeBakey Heart & Vascular Center: collaborator

Study Sites (46)

Palo Alto VA

Palo Alto, California, United States

Location

Stanford University

Stanford, California, 94305-2004, United States

Location

Atlanta VA Medical Center

Decatur, Georgia, United States

Location

Jesse Brown VA Medical Center

Chicago, Illinois, United States

Location

University of Kansas Medical Center

Lawrence, Kansas, United States

Location

Lexinton VA

Lexington, Kentucky, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, United States

Location

Baystate Medical Center

Springfield, Massachusetts, United States

Location

HealthEast St. Joseph's Hospital

Saint Paul, Minnesota, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Location

Centennial Heart

Nashville, Tennessee, United States

Location

Houston Methodist Hospital

Houston, Texas, United States

Location

University of Virginia

Charlottesville, Virginia, United States

Location

Peninsula Health

Frankston, Australia

Location

St. Vincent's Hospital Melbourne

Melbourne, Australia

Location

Concord Hospital

Sydney, Australia

Location

Royal North Shore

Sydney, Australia

Location

University of Sydney

Sydney, Australia

Location

Cardiovascular Center Aalst

Aalst, 9300 Aalst, Belgium

Location

Le'Centre Hospitalier de l'Universite de Montreal

Montreal, Canada

Location

York PCI Group INC

Ontario, Canada

Location

University of Ottawa Heart Institute

Ottawa, Canada

Location

Masaryk University and University Hospital Brno

Brno, Czechia

Location

Rigshospitalet University Hospital

Copenhagen, Denmark

Location

Cardiovascular Hospital

Lyon, France

Location

Hungarian Institute of Cardiology

Budapest, Hungary

Location

Vilnius University Hospital Santariskiu Klinikos

Vilnius, Lithuania

Location

Catharina Hospital Eindhoven

Eindhoven, 5623 EJ, Netherlands

Location

HagaZiekenhuis

The Hague, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

Waikato Hospital

Hamilton, New Zealand

Location

Stavanger University Hospital

Stavanger, Norway

Location

University Clinical Center of Serbia

Belgrade, Serbia

Location

Clinical Center Kragujevac

Kragujevac, Serbia

Location

Asan Medical Center

Seoul, South Korea

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Danderyds Sjukhus

Stockholm, Sweden

Location

Karolinska Institutet, Dep of clinical science and education, Södersjukhuset

Stockholm, Sweden

Location

Wales Heart Research Institute

Cardiff, United Kingdom

Location

University Hospitals Coventry and Warwickshire

Coventry and Warwickshire, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

St. Thomas' Hospital

London, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

Oxford University Hospital NHS Trust

Oxford, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southhampton, United Kingdom

Location

Related Publications (11)

• Zimmermann FM, De Bruyne B, Pijls NH, Desai M, Oldroyd KG, Park SJ, Reardon MJ, Wendler O, Woo J, Yeung AC, Fearon WF. Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2015 Oct;170(4):619-626.e2. doi: 10.1016/j.ahj.2015.06.024. Epub 2015 Jul 9.

  PMID: 26386784 BACKGROUND

• Zimmermann FM, De Bruyne B, Pijls NHJ, Desai M, Oldroyd KG, Reardon MJ, Wendler O, Woo J, Yeung AC, Fearon WF. A protocol update of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial: A comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2019 Aug;214:156-157. doi: 10.1016/j.ahj.2019.04.012. Epub 2019 Apr 29. No abstract available.

  PMID: 31207442 BACKGROUND

• Fearon WF, Zimmermann FM, De Bruyne B, Piroth Z, van Straten AHM, Szekely L, Davidavicius G, Kalinauskas G, Mansour S, Kharbanda R, Ostlund-Papadogeorgos N, Aminian A, Oldroyd KG, Al-Attar N, Jagic N, Dambrink JE, Kala P, Angeras O, MacCarthy P, Wendler O, Casselman F, Witt N, Mavromatis K, Miner SES, Sarma J, Engstrom T, Christiansen EH, Tonino PAL, Reardon MJ, Lu D, Ding VY, Kobayashi Y, Hlatky MA, Mahaffey KW, Desai M, Woo YJ, Yeung AC, Pijls NHJ; FAME 3 Investigators. Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery. N Engl J Med. 2022 Jan 13;386(2):128-137. doi: 10.1056/NEJMoa2112299. Epub 2021 Nov 4.

  PMID: 34735046 RESULT

• Fearon WF, Zimmermann FM, Ding VY, Takahashi K, Piroth Z, van Straten AHM, Szekely L, Davidavicius G, Kalinauskas G, Mansour S, Kharbanda R, Ostlund-Papadogeorgos N, Aminian A, Oldroyd KG, Al-Attar N, Jagic N, Dambrink JE, Kala P, Angeras O, MacCarthy P, Wendler O, Casselman F, Witt N, Mavromatis K, Miner SES, Sarma J, Engstrom T, Christiansen EH, Tonino PAL, Reardon MJ, Otsuki H, Kobayashi Y, Hlatky MA, Mahaffey KW, Desai M, Woo YJ, Yeung AC, Pijls NHJ, De Bruyne B. 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. Lancet. 2025 Apr 26;405(10488):1481-1490. doi: 10.1016/S0140-6736(25)00505-7. Epub 2025 Mar 30.

  PMID: 40174598 RESULT

• Takahashi K, Otsuki H, Zimmermann FM, Ding VY, Piroth Z, Oldroyd KG, Wendler O, Reardon MJ, Desai M, Woo YJ, Yeung AC, De Bruyne B, Pijls NHJ, Fearon WF; FAME 3 Trial Investigators. Outcomes After CABG Compared With FFR-Guided PCI in Patients Presenting With Acute Coronary Syndrome. JACC Cardiovasc Interv. 2025 Apr 14;18(7):838-848. doi: 10.1016/j.jcin.2025.01.434.

  PMID: 40240081 DERIVED

• Takahashi K, Otsuki H, Zimmermann FM, Ding VY, Engstrom T, Horsted Thyregod HG, Beleslin B, Putnik S, Tapp L, Barker T, Redwood S, Young C, Bech GJ, Hoohenkerk GJF, De Bruyne B, Pijls NHJ, Fearon WF; FAME 3 Trial Investigators. FFR-Guided Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting in Patients With Diabetes. JAMA Cardiol. 2025 Jun 1;10(6):603-608. doi: 10.1001/jamacardio.2025.0095.

  PMID: 40072460 DERIVED

• Takahashi K, Otsuki H, Zimmermann FM, Ding VY, Oldroyd KG, Wendler O, Reardon MJ, Woo YJ, Yeung AC, Pijls NHJ, De Bruyne B, Fearon WF; FAME 3 Trial Investigators. Sex Differences in Patients Undergoing FFR-Guided PCI or CABG in the FAME 3 Trial. JACC Cardiovasc Interv. 2025 Jan 27;18(2):157-167. doi: 10.1016/j.jcin.2024.09.030. Epub 2024 Dec 4.

  PMID: 39641725 DERIVED

• Otsuki H, Takahashi K, Zimmermann FM, Mavromatis K, Aminian A, Jagic N, Dambrink JE, Kala P, MacCarthy P, Witt N, Kobayashi Y, Takahashi T, Woo YJ, Yeung AC, De Bruyne B, Pijls NHJ, Fearon WF; FAME 3 Trial Investigators. Impact of a Chronic Total Occlusion on Outcomes After FFR-Guided PCI or Coronary Bypass Surgery: A FAME 3 Substudy. Circ Cardiovasc Interv. 2024 Nov;17(11):e014300. doi: 10.1161/CIRCINTERVENTIONS.124.014300. Epub 2024 Nov 6.

  PMID: 39502029 DERIVED

• Zimmermann FM, Ding VY, Pijls NHJ, Piroth Z, van Straten AHM, Szekely L, Davidavicius G, Kalinauskas G, Mansour S, Kharbanda R, Ostlund-Papadogeorgos N, Aminian A, Oldroyd KG, Al-Attar N, Jagic N, Dambrink JE, Kala P, Angeras O, MacCarthy P, Wendler O, Casselman F, Witt N, Mavromatis K, Miner SES, Sarma J, Engstrom T, Christiansen EH, Tonino PAL, Reardon MJ, Otsuki H, Kobayashi Y, Hlatky MA, Mahaffey KW, Desai M, Woo YJ, Yeung AC, De Bruyne B, Fearon WF; FAME 3 Investigators. Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial. Circulation. 2023 Sep 19;148(12):950-958. doi: 10.1161/CIRCULATIONAHA.123.065770. Epub 2023 Aug 21.

  PMID: 37602376 DERIVED

• Piroth Z, Otsuki H, Zimmermann FM, Ferenci T, Keulards DCJ, Yeung AC, Pijls NHJ, De Bruyne B, Fearon WF. Prognostic Value of Measuring Fractional Flow Reserve After Percutaneous Coronary Intervention in Patients With Complex Coronary Artery Disease: Insights From the FAME 3 Trial. Circ Cardiovasc Interv. 2022 Nov;15(11):884-891. doi: 10.1161/CIRCINTERVENTIONS.122.012542. Epub 2022 Sep 19.

  PMID: 36121706 DERIVED

• Fearon WF, Zimmermann FM, Ding VY, Zelis JM, Piroth Z, Davidavicius G, Mansour S, Kharbanda R, Ostlund-Papadogeorgos N, Oldroyd KG, Wendler O, Reardon MJ, Woo YJ, Yeung AC, Pijls NHJ, De Bruyne B, Desai M, Hlatky MA; FAME 3 Investigators. Quality of Life After Fractional Flow Reserve-Guided PCI Compared With Coronary Bypass Surgery. Circulation. 2022 May 31;145(22):1655-1662. doi: 10.1161/CIRCULATIONAHA.122.060049. Epub 2022 Apr 2.

  PMID: 35369704 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Coronary Disease; Coronary Stenosis

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Results Point of Contact

• Title: William Fearon, MD
• Organization: Stanford University

wfearon@stanford.edu

650-725-2621

Study Officials

• William F Fearon, MD

  Stanford University

  STUDY CHAIR

• Nico HJ Pijls, MD, PhD

  Catharina Hospital Eindhoven, The Netherlands

  PRINCIPAL INVESTIGATOR

• Bernard De Bruyne, MD, PhD

  VZW Cardiovascular Research Center Aalst

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: April 1, 2014
• Study Start: August 25, 2014
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2024
• Last Updated: March 17, 2026
• Results First Posted: January 20, 2022

Record last verified: 2025-03

Locations

BE (1); GB (8); KR (1); NL (3); CA (3); DK (1); NO (1); AU (5); US (13); FR (1); CZ (1); HU (1); LI (1); NZ (1); SE (3)