Percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) did not meet non-inferiority for one-year adverse events compared to coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease, primary results of the FAME 3 (Fractional flow reserve versus angiography for multivessel evaluation) trial have shown.
The results were presented during a late-breaking trial session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual) by William Fearon (Stanford University School of Medicine, Department of Medicine, Stanford Cardiovascular Institute, Stanford, USA) and published simultaneously in the New England Journal of Medicine. Fearon told TCT attendees that in patients with more complex, three-vessel coronary artery disease, CABG remains the treatment of choice
However, the study’s investigators also reported that in patients with a low SYNTAX score there was less incidence of adverse events compared to those with intermediate or high SYNTAX scores, and in this cohort of patients PCI performed more favourably.
In patients with three-vessel coronary artery disease (3V-CAD), previous studies have demonstrated improved outcomes with CABG compared with PCI. However, most of the trials used bare-metal or first-generation drug-eluting stents (DES) and none of them utilised measurement of FFR to guide PCI.
FAME 3 was a multicentre, international, randomised, controlled non-inferiority trial in which patients with three-vessel CAD warranting revascularisation were randomly assigned to PCI or CABG. PCI was performed with current generation zotarolimus-eluting stents guided by FFR measurement and CABG was performed with the recommendation to use multiple arterial grafts.
A total of 1,500 patients were randomised 1:1 to either CABG based on coronary angiogram or FFR-guided PCI in all lesions with an FFR ≤0.80 at 48 centres in Europe, North America, Australia, and Asia. For inclusion in the trial, patients had three-vessel 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 revascularisation 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 primary endpoint of the one-year rate of death, myocardial infarction, stroke, and repeat revascularisation (MACCE) was 10.6% for PCI and 6.9% for CABG (hazard ratio [HR] 1.5, 95% CI 1.1‒2.2, p=0.35 for non-inferiority). The one-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 revascularisation (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 rehospitalisation within 30 days were all lower with PCI compared to CABG.
When patient data was analysed based on SYNTAX score, the one-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=0.02.
“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 favourably in comparison with CABG in three-vessel coronary artery disease with less complex disease according to the SYNTAX score,” said Fearon. “In patients with more complex three-vessel coronary artery disease, CABG remains the treatment of choice.”
In a press conference following the presentation of the results at TCT, Fearon was asked to comment on the implications of the study’s findings for PCI in multivessel disease.
In his response, Fearon said: “I think that the study provides physicians and patients more contemporary data and information on options and expected outcomes in patients with multivessel disease. If you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI. If you have more complex disease, at least based on the outcomes here—which included repeat revascularisation—bypass outperformed PCI. I think that there are still patients that look at trade-offs, and some patients will accept a higher event rate in order to avoid a long recovery and vice versa. I think it allows patients and physicians to make more informed decisions.”
David Kandzari (Piedmont Heart Institute, Atlanta, USA) asked to account for the improvements observed in the CABG arm. Fearon suggested that improved operative techniques or better adherence to medical therapy may explain the differences.
“When we compare the characteristics of patients in FAME 3 to SYNTAX, they are a very similar age, sex, risk factors, SYNTAX Score,” Fearon commented. “I think it may be better operative techniques, but one thing we did notice is that, the adherence to medical therapy was better in FAME 3, for example in SYNTAX at one year, 70% of patients were on a statin, in FAME 3 it was 94% and beta blockers were in the 75% range in SYNTAX, and 83% in FAME 3. I think adherence to medical therapy may be part to explain the very good outcomes in the CABG arm.“