FARGO: No Gain With FFR Over Angiography in Multivessel CABG

Patrice Wendling

November 30, 2018

New research suggests that the benefits associated with fractional flow reserve (FFR) assessment in patients with multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI) might not extend to their counterparts referred for surgery.

Coronary artery bypass grafting (CABG) guided by FFR readings resulted in graft failure rates and clinical outcomes at 6 months similar to those with CABG guided by standard coronary angiography in the prospective FARGO study.

The study was published online in the Journal of the American College of Cardiology.

Perhaps the most intriguing finding, however, was a significant decline in mean FFR from baseline for lesions with FFR greater than 0.80 in which grafting was deferred (0.89 vs 0.81; P = .002).

Although regression toward the mean could explain the measurement, it's unlikely an accidental finding, lead author Anne Langhoff Theusen, MD, Odense University Hospital, Denmark, told theheart.org  | Medscape Cardiology.

"We found that in many of these lesions that we deferred, stenosis had increased," she said. "There was more atherosclerosis in the artery and many of these patients also had angina or positive cardiac scintigraphy."

The finding was unexpected, said Theusen, as the DEFER and FAME studies reported that nonsignificant stenosis can be safely deferred in PCI-treated patients and that FFR-guided PCI confers clinical benefits similar to or better than angiography-guided PCI.

Although FFR is used in routine practice to help determine whether patients with MVD should undergo PCI or CABG, the Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization (FARGO) trial is the first prospective randomized trial to evaluate FFR and angiography in the context of CABG.

"FFR appears as a good refinement tool to improve PCI decision; but considering this first set of randomized data in CABG patients, FFR may be of lesser interest in patients oriented toward CABG surgery," Gilles Montalescot, MD, PhD, and Benoit Lattuca, MD, both from Pitié-Salpêtrière University Hospital, Paris, write in an accompanying editorial.

They note the paucity of evidence addressing this important clinical question and that the recent FUTURE trial even suggested harm with an FFR-guided strategy, more than doubling the risk for all-cause death compared with angiography-guided revascularization.

FARGO was stopped early because of slower-than-expected enrolment. One hundred patients referred for CABG at three university hospitals in Denmark were randomly assigned to FFR-guided or angiography-guided CABG. The heart team designed a graft plan for all patients based on index angiography. FFR measurements were obtained in 97 patients. For the FFR-guided group, lesions with FFR greater than 0.80 were deferred and a new graft plan was created.

All patients had two- or three-vessel disease and most had stable angina. Mean FFR at index was 0.78 in the FFR group and 0.77 in the angiography group.

A total of 267 coronary arteries were grafted, 37% of which were arterial grafts. Angiographic follow-up after 6 months was available for 72 patients.

The primary end point of graft failures, defined as all grafts with less than TIMI flow grade 3 and/or anastomosis stenosis greater than 50%, occurred in 16% of the FFR group and 12% of the angiography group (P = .97).

The FFR and angiography groups also had similar rates of death (0 vs 4 events), myocardial infarction (2 vs 0 events), and stroke (4 vs 2 events).

The rate of revascularization before follow-up was similar, at six events in each group. An unpublished follow-up analysis beyond the 6-month study period, however, showed more revascularizations among patients with deferred lesions in the FFR group compared with the angiography group (12 vs 6; = .05), Theusen said.

"The take-home message is that we found that FFR is not better than angiography to guide CABG," she said. "It's okay to use FFR in CABG, but one should be aware of increasing atherosclerotic disease in these deferred lesions."

That said, Theusen cautioned that "we need larger studies with longer-term follow-up."

The investigators noted that surgeons could not comply with the graft plan in 12% of patients, mostly because of the small caliber of the coronary arteries or lack of grafting material. Twenty patients also did not return for follow-up angiography, which could introduce potential bias.

Montalescot and Lattuca write that the "results must be interpreted very cautiously," citing the small study size, graft plan deviations, loss of patients to follow-up of the primary end point, and the high likelihood of a type II error.

"Nevertheless, the raw results are not in favor of the FFR-guided CABG strategy and there is an unsettling significant reduction of FFR after 6 months for the deferred lesions with the FFR-guided strategy leading to more new PCI in this group," they write.

Further trials are warranted, they say, with the ongoing roughly 200-patient GRAFFITI (Graft Patency After FFR-guided Versus Angio-guided CABG) trial likely to provide insights on the role of FFR in CABG.

"In conclusion, the lessons learned from the FFR trials in PCI may not be extrapolated to CABG patients," Montalescot and Lattuca write. "For now, and while awaiting further information, the ultimate goal of CABG surgery remains to anatomically complete revascularization using arterial conduits preferentially if not exclusively. This once-for-all surgical treatment may lead to a few more anastomoses than functionally needed but at no clinical cost for the patient."

Thuesen reports a fellowship from the Danish Heart Foundation, the University of Southern Denmark, and the Region of Southern Denmark . Montalescot reports grants from Abbott, Amgen, Actelion, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham and Women's Hospital, Cardiovascular Research Foundation, Daiichi-Sankyo, Idorsia, Lilly, Europa, Elsevier, Fédération Française de Cardiologie, ICAN, Medtronic, Journal of the American College of Cardiology, Lead-Up, Menarini, MSD, Novo-Nordisk, Pfizer, Sanofi, Servier, the Mount Sinai School, TIMI Study Group, and WebMD, publisher of Medscape. Lattuca reports grants from Biotronik, Daiichi-Sankyo, and Fédération Française de Cardiologie; and personal fees from Daiichi-Sankyo, Eli Lilly, and Novartis.

J Am Coll Cardiol. 2018;72:2732-2743, 2744-2746. Abstract, Editorial

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.


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