Key Points:
- The FAME 3 trial tested whether percutaneous coronary intervention (PCI) could offer comparable long-term outcomes to coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease by limiting intervention to flow-limiting lesions as determined by fractional flow reserve (FFR)
- Among 1,500 patients, FFR-guided PCI as compared to CABG had similar death and stroke rates but PCI resulted in higher rates of myocardial infarction and repeat revascularization.
- These findings support shared decision-making in selecting revascularization strategies, highlighting the evolution of PCI outcomes in contemporary practice.
The long-term balance of risk and benefit between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for multivessel coronary artery disease remains an area of continued clinical debate. While CABG has traditionally been favored for long-term outcomes, newer stent technology, the use of fractional flow reserve (FFR), and improved medical therapy have changed the landscape of PCI. The final 5-year results of the FAME-3 trial was presented at the ACC 2025 Scientific Sessions and simultaneously published in The Lancet.
In this randomized, investigator-initiated clinical trial, 1,500 patients across 48 centers in Europe, North America, Australia, and Asia with three-vessel coronary artery disease (excluding left main disease) were assigned to either FFR-guided PCI with drug eluting stents or to CABG. Only lesions with FFR ≤ 0.80 were treated with PCI. For the CABG group, LIMA grafts were attempted in all cases and complete arterial revascularization was strongly recommended. The median age was 65 years old, 82% were male, 93% were White, and 40% presented as acute coronary syndromes.
At five years, the primary composite endpoint of death, stroke, or myocardial infarction occurred in 16% of PCI patients and 14% of CABG patients (HR 1.16; 95% CI 0.89–1.52; p=0.27). There was no difference in all-cause mortality (7% vs. 7%, p=0.99) or stroke (2% vs. 3%, p=0.65). Patients receiving PCI experienced higher rates of myocardial infarction (8% vs. 5%, HR 1.57; 95% CI 1.04-2.36) and repeat revascularization (16% vs. 8%, HR 2.02; 95% CI 1.46-2.79). Medical therapy use at 5 years were similar between both groups. Interestingly, subgroup analysis revealed that PCI outcomes were especially favorable in patients with lower SYNTAX scores.
Limitations of the study include that the primary endpoint at 5 years was a prespecified secondary endpoint that the trial was not powered for. Further, the prespecified hypothesis of non-inferiority between FFR-guided PCI and CABG on composite MI, stroke, and death at 1 year was not met as previously published by the FAME 3 group in 2022. Additionally, there was limited use of intravascular imaging in the PCI arm (12%) and there was underrepresentation of women and non-White patients.
“This is the only study to compare CABG and PCI as they are currently used in cardiology–– incorporating recent advances in surgical and minimally invasive techniques as well as in medical therapy––in patients with triple-vessel disease,” said lead investigator Dr. William F. Fearon of Stanford University. He also noted that “these findings support better-informed shared decision-making between patients and their clinicians.”
While CABG remains more durable in terms of reintervention and myocardial infarction risk, the absence of a significant difference in death, stroke, or MI—coupled with PCI’s less invasive nature and reduced length of hospital stay—may shift the conversation toward individualized patient preference.
