Not all that surprising
“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.
“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.
Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.
In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”
Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”
Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”
The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.
The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.
FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
Did the primary endpoint favor CABG?
At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”
M. Alexander Otto, MDedge News
Dr. Roxana Mehran
It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.
Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).
Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.
Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”
And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.
“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”
FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.
A version of this article first appeared on Medscape.com.