Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 3 Extended

Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 3 Extended A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease

Coronary artery disease, or narrowing of the blood vessels that provide blood to the heart, is the most common cause of death in the United States and can be treated with either coronary bypass surgery or coronary stent placement. This study will evaluate outcomes, including death and quality of life, at 10 years in 1,500 patients with coronary disease who have already been randomized to either bypass surgery or stenting.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Procedure: FFR-guided PCI; Procedure: CABG

Detailed Description

Coronary artery disease (CAD) remains the major cause of morbidity and mortality in adults in the United States. In patients with 3-vessel CAD not involving the left main coronary artery, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) can improve outcomes. Older studies have shown that the more invasive option, CABG, significantly reduces mortality during long-term follow-up compared with PCI. However, these studies did not use contemporary methods to perform PCI, such as measuring an index called fractional flow reserve (FFR) with a coronary pressure wire or using current- generation drug-eluting stents (DES), both of which significantly improve outcomes after PCI. The Fractional flow reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial randomized 1,500 patients to FFR-guided PCI with current generation DES or to CABG and found that at 5 years there was no significant difference in the composite of death, myocardial infarction (MI) or stroke between the two strategies. There was a reduction in MI in the CABG group. Longer-term follow-up is critical to determine if contemporary PCI results in similar survival as CABG. The primary aim of this project is to determine if 10-year mortality is different after FFR-guided PCI compared with CABG. Investigators will perform 10-year follow-up in the 1,500 patients randomized in the FAME 3 trial to determine if FFR-guided PCI is non-inferior to CABG with respect to mortality. Secondary aims include assessing quality of life and angina relief at 10 years in the two groups. Additionally, investigators will compare individual rates of secondary clinical outcomes including MI, stroke, and repeat revascularization at 10-year follow-up after PCI or CABG.

• Study Type: Observational
• Enrollment (Actual): 1500

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study will evaluate outcomes, including death and quality of life, at 10 years in 1,500 patients with coronary disease who have already been randomized to either bypass surgery or stenting.

Description

Inclusion Criteria:

1. Age ≥ 21 years with angina and/or evidence of myocardial ischemia

2. 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

3. Willing and able to provide informed, written consent

Exclusion Criteria:

1. Requirement for other cardiac or non-cardiac surgical procedure (e.g., valve replacement, carotid revascularization), however a maze procedure or pulmonary vein isolation is allowed
2. Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
3. Recent STEMI (<5 days prior to randomization)
4. Ongoing Non STEMI with biomarkers (cardiac troponin) still rising
5. Known left ventricular ejection fraction <30%
6. Life expectancy < 2 years
7. Requiring renal replacement therapy
8. Undergoing evaluation for organ transplantation
9. Participation or planned participation in another clinical trial, except for observational registries
10. Pregnancy
11. Inability to take dual antiplatelet therapy or anticoagulation and single antiplatelet therapy for at least six months
12. Previous CABG
13. Left main disease requiring revascularization
14. Extremely calcified or tortuous vessels precluding FFR measurement
15. Any target lesion with in-stent drug-eluting stent restenosis
16. More than one major epicardial vessel which is chronically occluded

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FFR-guided PCI group; These patients have undergone fractional flow reserve-guided percutaneous coronary intervention	Procedure: FFR-guided PCI; Coronary stenting compared with coronary bypass surgery
CABG group; These patients underwent coronary artery bypass grafting surgery	Procedure: CABG; Coronary artery bypass surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	The primary outcome is mortality or overall survival	10-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Secondary aims include assessing quality of life at 10 years in the two groups utilizing the EQ-5D quality of life questionnaire.	10-year follow-up
Angina Relief	Secondary aims include assessing angina status at 10 years in the two groups utilizing the Seattle Angina Questionnaire.	10 year follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac events	Additionally, we will compare individual rates of secondary clinical outcomes including myocardial infarction (MI), stroke, and repeat revascularization and combinations of the above, including death and MI, and death, MI, or stroke at 10-year follow-up after PCI or CABG.	10 year follow-up

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: December 19, 2025
• First Submitted That Met QC Criteria: December 26, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: PCI; stroke; quality of life; coronary artery disease; angina; myocardial infarction; CABG; clinical trial; stent; coronary artery bypass; multicenter; cardiac death; FFR-guided PCI; repeat revascularization; long term mortality; 3-vessel CAD; 10-year mortality
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Ischemia; Chest Pain; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stroke; Coronary Artery Disease; Death; Myocardial Infarction; Angina Pectoris
• Other Study ID Numbers: 83374; 1R01HL179196-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No