CABG Wins Again for Multivessel Disease
By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: Fractional flow reserve-guided percutaneous coronary intervention failed to meet noninferiority guidelines vs. coronary artery bypass grafting.
SOURCE: Fearon WF, Zimmermann FM, De Bruyne B, et al. Fractional flow reserve-guided PCI as compared with coronary bypass surgery. N Engl J Med 2022;386:128-137.
Over the years, numerous investigators have sought to compare outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in multivessel coronary artery disease. With few exceptions, these trials have indicated CABG results in lower rates of repeat revascularization and spontaneous myocardial infarction (MI). A mortality advantage to CABG has been ascribed to diabetic patients specifically. The results of the 2009 SYNTAX trial suggested an increasing benefit of CABG associated with higher complexity of coronary anatomy.1
The FAME 3 trial was planned as a rematch of sorts, based primarily on two advances in the PCI realm. There might be better outcomes with PCI guided by fractional flow reserve (FFR) rather than by angiography alone. Newer (second-generation) drug-eluting stents (DES) might be better than the first-generation devices used in SYNTAX and other prior investigations regarding both early and late outcomes.
In this multinational trial, Fearon et al randomized 1:1 1,500 patients with multivessel coronary disease to FFR-guided PCI or to CABG at 48 centers. A total of 757 patients were assigned to PCI and 743 to CABG. Enrolled patients were a mean age of 65 years, more than 80% were men, and more than 90% were white. Twenty-eight percent of patients were diabetic, and 39% had presented with acute coronary syndrome. Patients with significant obstructive disease of the left main coronary artery were excluded, as were patients with recent ST-elevation MI, cardiogenic shock, and ejection fraction less than 30%. Importantly, other markers of PCI complexity were not excluded, with 22% of patients showing at least one chronic total occlusion, and 68% showing at least one bifurcation lesion. FFR was measured in 82% of lesions in the PCI group, and resulted in deferring PCI in 24% of cases. FFR was measured in only 10% of patients in the CABG group, in accordance with the intent of the trial.
At one year, the incidence of the primary endpoint (a composite of death from any cause, stroke, MI, or repeat revascularization) was 10.6% in the PCI group and 6.9% among patients assigned to CABG (HR, 1.5; 95% CI, 1.1-2.2; P = 0.35 for noninferiority). The incidence of each component of the primary endpoint did not differ significantly between groups. Procedure-related complications were higher in the CABG group. Hospital length of stay was longer, and CABG patients also recorded higher rates of major bleeding, arrhythmia, acute kidney injury, and rehospitalization within 30 days. The authors reported that in patients with multivessel coronary artery disease, FFR-guided PCI did not meet the set criteria for noninferiority with respect to major adverse cardiac or cerebrovascular events at one year.
It should not surprise us that CABG retains an advantage over PCI for clinical outcomes in multivessel disease. With each incremental advance in technique, proponents of PCI have argued older trials, such as SYNTAX, are no longer relevant. In this case, application of both current-generation DES and FFR guidance did not result in noninferiority of PCI compared with CABG. While a post-hoc analysis suggested PCI was noninferior in patients with low procedural complexity, as defined by SYNTAX score < 22, any subgroup analysis should be viewed as hypothesis-generating only. The current publication reports results at only 12 months. Prior data suggest the advantage of CABG becomes greater over time; this trial has planned three- and five-year follow-up intervals, and most expect the gap to grow wider at those points. In this trial, the use of intravascular imaging (i.e., intravascular ultrasound [IVUS] and optical coherence tomography) was low (12%). Separate data suggest using such imaging can improve hard outcomes after PCI. However, the low penetration of imaging in this trial closely mirrors real-world use in the United States. Therefore, although we may speculate at how mandated use of IVUS might have changed outcomes in FAME 3, the results in this case are broadly applicable to current clinical practice.
In FAME 3, the use of FFR resulted in fewer lesions deferred (24%) vs. prior iterations of FAME, in which more than one-third of angiographically questionable lesions were deferred. Because the advantage of FFR guidance is thought to be related to the ability to avoid unnecessary interventions and their related complications, the benefits of FFR here were less than had been projected. Additionally, compared with prior trials of revascularization for multivessel disease, medical outcomes were better in both arms. Overall, the one-year mortality rate in the PCI arm was lower than in SYNTAX (1.6% vs. 4.4%), and subsequent revascularization was dramatically lower (4.9% vs. 13.5%). Still, surgery came out on top. We should not discount the fact surgical techniques continue to improve in parallel with PCI, and that medical therapy also has improved. Adherence to beta-blockers was higher in FAME 3 vs. SYNTAX.
When considering options for individual patients, we should recognize the absolute difference in outcomes here was small. While CABG should be a primary consideration for patients with multivessel coronary disease who carry favorable surgical risk, that does not obviate the need for a patient-centric approach to decision-making. Not all patients will make the same decision in the face of an open discussion about the tradeoffs between short-term procedural outcomes and longer-term major adverse cardiovascular events. Lastly, we should acknowledge medical therapy without revascularization was not included in this trial and may be an appropriate path for some patients, too.
- Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961-972.
Fractional flow reserve-guided percutaneous coronary intervention failed to meet noninferiority guidelines vs. coronary artery bypass grafting.
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