FAME 3 Trial Compares FFR-Guided PCI Versus CABG in Three-Vessel CAD

November 4, 2021—The primary results of FAME 3, the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3 trial, found that percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) did not meet noninferiority for 1-year adverse events compared to coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3V-CAD).

Patients with a low SYNTAX score, which measures the complexity of CAD, had less incidence of adverse events compared to those patients with intermediate or high SYNTAX scores. In this cohort of patients, PCI performed more favorably.

The FAME 3 findings were reported at TCT 2021, the 33rd annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation, and published simultaneously online by William F. Fearon, MD, et al in The New England Journal of Medicine.

As noted in the TCT press release, previous studies have shown improved outcomes in patients with 3V-CAD with CABG compared with PCI. However, most of the trials used bare metal or first-generation drug-eluting stents (DES) and none of them utilized measurement of FFR to guide PCI.

FAME 3 was a multicenter, international, randomized, controlled noninferiority trial in which patients with 3V-CAD warranting revascularization were randomly assigned to PCI or CABG. PCI was performed with current-generation zotarolimus-eluting stents guided by FFR measurement. CABG was performed with the recommendation to use multiple arterial grafts.

According to TCT, a total of 1,500 patients in FAME 3 were randomized 1:1 to either CABG based on coronary angiogram or FFR-guided PCI in all lesions with an FFR ≤ 0.80 at 48 centers in Europe, North America, Australia, and Asia.

For inclusion in the trial, patients had 3V-CAD, defined as ≥ 50% diameter stenosis by visual estimation in each of the three major epicardial vessels, but not involving the left main coronary artery, and amenable to revascularization by both PCI and CABG as determined by the Heart Team. A total of 757 patients underwent FFR-guided PCI and 743 received CABG.

The TCT announcement summarized the findings for PCI versus CABG as follows:

• The primary endpoint of the 1-year rate of death, myocardial infarction (MI), stroke, and repeat revascularization (major adverse cardiovascular and cerebrovascular events [MACCE]) was 10.6% vs 6.9% (hazard ratio, 1.5; 95% CI 1.1-2.2; P = .35 for noninferiority)
• The 1-year rate of death (1.6% vs 0.9%), MI (5.2% vs 3.5%), and stroke (0.9% vs 1.1%) were not significantly different between the two strategies
• Repeat revascularization (5.9% vs 3.9%) was higher in the PCI group
• Safety endpoints of BARC type 3-5 bleeding, acute kidney injury, atrial fibrillation/arrhythmia, and rehospitalization within 30 days were all lower with PCI compared to CABG

When patient data were analyzed based on SYNTAX score, the 1-year MACCE rate was lower for PCI compared with CABG for patients with a low SYNTAX score (5.5% vs 8.6%) but higher with PCI compared with CABG for both intermediate (13.7% vs 6.1%) and high SYNTAX scores (12.1% vs 6.6%) with P for interaction by SYNTAX score = .02, reported TCT in the announcement.

“The 1-year rate of death, MI, or stroke was not significantly different between the two strategies,” commented Dr. Fearon in the TCT press release. “However, FFR-guided PCI with a current-generation DES performed favorably in comparison with CABG in 3V-CAD with less complex disease according to the SYNTAX score.”

“In patients with more complex 3V-CAD, CABG remains the treatment of choice,” concluded Dr. Fearon, who is Professor of Medicine (Cardiology) and Director of Interventional Cardiology at Stanford University School of Medicine and the Chief of the Cardiology Section at the VA Palo Alto Health Care System in Palo Alto, California.