When to Take the Patient Off the Table: FFR-Guided PCI Not Non-Inferior to CABG in 3-Vessel Disease

Data presented at the Transcatheter Cardiovascular Therapeutics (TCT2021) conference and published in the New England Journal of Medicine found that among individuals with three-vessel coronary artery disease, percutaneous coronary intervention (PCI) guided by FFR (fractional flow reserve) was not non-inferior to coronary artery bypass graft surgery (CABG).1

FFR allows for nuanced assessment of intermediate severity coronary artery stenoses by adding physiologic flow data and predicting clinical relevance of angiographically significant stenoses. FFR invasively assesses the hemodynamic impact of a coronary disease, thereby adding to the anatomic assessment made by coronary angiography, to determine the utility of revascularization. However, recent data has not uniformly shown FFR to have mortality benefit over an angiography-guided revascularization strategy.2

The FAME-3 Study

The FAME-3 investigators, led by Drs. William Fearon and Frederik Zimmerman, assessed whether FFR-guided PCI was non-inferior to CABG in 1,500 patients for a composite endpoint of death from any cause, myocardial infarction, stroke, or repeat revascularization at one year. They excluded patients with recent ST-segment elevation myocardial infarction, cardiogenic shock, and a left ventricular ejection fraction under 30%. Of note, trial participants had a mean age of 65 years and were predominantly male (~82%) and white (~93%), raising concern for external validity to the broader national and international population.

The study demonstrated a hazard ratio of 1.5 for the primary composite outcome in FFR-guided PCI (10.6% event rate) vs. CABG (6.9% event rate), rebutting the hypothesis of non-inferiority of PCI in this population. In secondary analysis, results were particularly pronounced among individuals with higher SYNTAX scores, diabetes, prior PCI, and age <65 years. The CABG group did experience a statistically significant increase in major bleeding, AKI, clinically significant arrhythmia, and rehospitalization within 30 days.

Of note, only 11% of patients underwent intracoronary imaging during PCI, substantially below the modern standard of care. Intracoronary imaging, including intravascular ultrasound and optical coherence tomography, may guide stent landing zones, detect stent malposition, and maximize stent expansion. Meta-analyses have demonstrated reduction in major adverse cardiac events, repeat revascularization, and restenosis with the use of intracoronary imaging.3,4 Future studies may seek to increase of intracoronary imaging in PCI.

The investigators provide compelling evidence that for individuals with three vessel coronary artery disease, particularly in diabetic and lower surgical risk patients, CABG remains the preferred revascularization strategy. Despite short-term increases in major bleeding and arrhythmia with CABG, one year data continues to favor CABG for more complex coronary artery disease. Consistent with prior data, subgroup analysis showed that PCI in those with lower coronary disease complexity (as determined by SYNTAX score) may have a role, particularly in those with high surgical risk, though this remains hypothesis generating.

Notably FAME-3 was not designed to test the superiority of either revascularization approach. In practice, the management of complex coronary disease benefits from engaging an experienced multidisciplinary team and shared decision-making with patients.


  1. Fearon WF, Zimmerman FM, et al. Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery. N Engl J Med. 2021 Nov 4. doi:10.1056/NEJMoa2112299. Online ahead of print.
  2. Puymirat E, et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021 Jul 22;385(4):297-308.
  3. Casella G, et al. Impact of intravascular ultrasound-guided stenting on long-term clinical outcome: a meta-analysis of available studies comparing intravascular ultrasound-guided and angiographically guided stenting. Catheter Cardiovasc Interv. 2003;59:314-21.
  4. Parise H, et al. Meta-analysis of randomized studies comparing intravascular ultrasound versus angiographic guidance of percutaneous coronary intervention in pre-drug-eluting stent era. Am J Cardiol. 2011;107:374-82.