FFR-Guided PCI Fails to Prove Noninferiority to CABG in FAME 3

Data from the FAME 3 trial cast doubt on the role of FFR-guided PCI versus CABG among patients with 3-vessel coronary artery disease.

Results of the FAME 3 trial indicate percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) failed to meet noninferiority compared to coronary artery bypass grafting (CABG) among patients with 3-vessel coronary artery disease (CAD).

Presented at the TCT 2021, the 33rd annual scientific symposium of the Cardiovascular Research Foundation (CRF), results of the trial demonstrate FFR-guided failed to demonstrate noninferiority to CABG for incidence of a composite outcome of death, myocardial infarction, stroke, or repeat revascularization at 1 year.

“The one-year rate of death, MI, or stroke was not significantly different between the two strategies. However, FFR-guided PCI with a current generation drug-eluting stent performed favorably in comparison with CABG in three-vessel coronary artery disease with less complex disease according to the SYNTAX score,” said William F. Fearon, MD, professor of medicine and director of interventional cardiology at Stanford University School of Medicine, in a statement. “In patients with more complex three-vessel coronary artery disease, CABG remains the treatment of choice.”

Supported with funding from Medtronic and Abbott Vascular, the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial was designed as a multicenter, international, noninferiority trial comparing outcomes among patients with 3-vessel CAD randomized to CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. Conducted across 48 centers, a total of 1500 patients were randomized in the trial and followed for the primary end point, which was defined as the incidence of a composite outcome including all-cause mortality, myocardial infarction, stroke, or repeat revascularization at 1-year.

Secondary outcomes of interest for the study included a composite of death, myocardial infarction or stroke. Safety end points of interest included BARC type 3-5 bleeding, acute kidney injury, atrial fibrillation or clinically significant arrhythmia, definite stent thrombosis, symptomatic graft occlusion, and rehospitalization within 30 days. For the purpose of analysis, noninferiority was defined as an upper boundary of less than 1.65 for the 95% CI of the hazard ratio.

Of 1500 randomized in the trial, 757 were randomized to undergo PCI and 743 were randomized to undergo CABG. The mean age of patients randomized in the trial was 65 years, 29% had diabetes, 39% presented with an acute coronary syndrome, and 13% had undergone previous PCI. Investigators also noted the mean number of lesions per patient was 4.3, 22% of patients had at least 1 vessel with chronic total occlusion, and 68% had at least 1 bifurcation lesion. Additionally, the mean SYNTAX score among patients included in the trial was 26.

Upon analysis, results suggested the 1-year incidence of the composite primary end point was 10.6% among the FFR-guided PCI arm compared to 6.9% among the CABG arm of trial (HR, 1.5 [95% CI, 1.1-2.2]; P for noninferiority=.35). Investigators pointed out there was no evidence of between-group differences in the indigence of each individual component of the composite primary end point.

Further analysis into the incidence of secondary outcome measures revealed the incidence of death, myocardial infarction, or stroke was 7.3% among the FFR-guided PCI arm of the trial and 5.2% among the CABG arm (HR, 1.4 [95% CI, 0.9-2.1]). Of note, patients who were assigned to undergo CABG had longer hospital stays and higher incidences of major bleeding, arrhythmia, acute kidney injury, and rehospitalization within 30 days.

This study was presented at TCT 2021 as “FAME 3: A Randomized Trial of FFR-Guided Stenting Compared With CABG,” and simultaneously published as “Fractional Flow Reserve–Guided PCI as Compared with Coronary Bypass Surgery,” in the New England Journal of Medicine.