FFR Can Safely Guide PCI Deferral, With Solid Long-term Results: J-CONFIRM

Deferral of revascularization based on fractional flow reserve (FFR) is indeed a safe strategy, the multicenter J-CONFIRM registry reassures. Among more than 1,200 Japanese patients who postponed intervention, fewer than half a percent died of cardiac causes or experienced target-vessel MI by 2 years.

FAME and DEFER, both randomized controlled trials, “have shown the safety and feasibility of FFR-based deferral of revascularization, whereas there is little prospective large-scale data evaluating them in real-world practice,” lead author Shoichi Kuramitsu, MD, PhD (Kokura Memorial Hospital, Kitakyushu, Japan), and colleagues point out in their paper published online this week in Circulation: Cardiovascular Interventions.

William Fearon, MD (Stanford University School of Medicine, CA), a principal investigator of FAME, said that this report fills a gap.

“This is an important study because it confirms in a real-world registry what was shown in the long-term follow-up of the randomized DEFER trial and FAME 2 trial, as well as the single-center registry looking at deferred proximal LAD lesions based on FFR: that deferral of revascularization based on FFR is very safe,” Fearon told TCTMD via email.

Commenting for TCTMD, Nico Pijls, MD, PhD (Catharina Hospital Eindhoven, the Netherlands), also a FAME principal investigator, agreed. “In my view, deferring lesions on the basis of FFR has been well established, but of course additional data are always welcome,” he said.

Both Pijls and Fearon pointed out, though, that J-CONFIRM offers fresh insights, particularly when it comes to gradations in FFR and patient outcome.

Few Cardiac Deaths or Target-Vessel MIs

J-CONFIRM enrolled 1,263 patients (1,447 lesions) at 28 Japanese centers between September 2013 and June 2015. All had undergone FFR and, based on those findings, did not undergo immediate revascularization. Mean FFR was 0.86.

The 2-year rate of target-vessel failure (TVF), the study’s primary endpoint, was 5.5% in deferred lesions, almost entirely due to clinically driven TVR (5.2%). Cardiac death and target-vessel MI were rare, each occurring at rates of 0.41% over follow-up.

Importantly, TVF showed an inverse association with FFR: the lower the baseline FFR value, the higher the 2-year risk. This inverse relationship was seen in the proximal location, but not in the distal. Proximal lesions with FFR values of ≤ 0.75, 0.76 to 0.80, 0.81 to 0.90, and ≥ 0.91 had 2-year TVF rates of 14.7%, 8.9%, 5.0%, and 4.4%, respectively.

Independent predictors of TVF were FFR value (HR 1.07 per 0.01 decrease; 95% CI 1.04-1.11), lesion location in the left main (HR 5.89; 95% CI 2.72-12.80), moderate-to-severe lesion calcification (HR 2.49; 95% CI 1.36-4.58), hemodialysis (HR 2.90; 95% CI 1.11-7.58), and lesion location in the right coronary artery (HR 1.78; 95% CI 1.02-3.11).

Thus, “careful follow-up may be required in patients” with these characteristics, the researchers advise.

Implications of an FFR Continuum

The concept of FFR as a continuum hasn’t been as precisely explored in earlier studies, Pijls observed. “Of course we could suspect that [it existed] because in nature there is always a continuum. There are no binary things in nature. But it is [good] to see it.”

Fearon outlined the clinical implications, noting: “In general, when the FFR is below 0.75-0.80, the risk of PCI is less than the risk of lesion progression and adverse events, so revascularization makes sense if it can be performed safely.”

Furthermore, he added, the J-CONFIRM event rates fall below what has been seen in 2-year follow-up of studies comparing various current-generation DES. “In other words,” he explained, “the risk of acute and chronic complications from PCI (even with current-generation DES) is greater than the risk of lesion progression and an adverse event when the FFR is > 0.80.”

It is the presence of ischemia that determines the outcome of the patient. Nico Pijls

For Pijls, all of the above is interesting given the debates over medical therapy versus PCI sparked by the ISCHEMIA trial. “What is confirmed by [J-CONFIRM] is that it is the presence of ischemia that determines the outcome of the patient. If there is no ischemia present—that correlates to a high value of FFR—then the outcome is [fine] with medical treatment. And if there is ischemia it is better to do a PCI,” he commented.

One other point of interest is that maximum hyperemia was induced during FFR measurement, said Pijls. “Full hyperemia, as was used in this Japanese study, is really important to optimize the outcome.”

Asked by TCTMD about how the use of FFR might differ between Japan and other regions, Pijls described it as “equal.”

The main difference, he clarified, is that “on average Japanese people have somewhat smaller coronary arteries, and I think it is very valuable to have confirmed that also in a group of only people in Japan, you find these excellent results.”

Fearon mentioned an additional nuance: “One caveat is that the spontaneous MI rate was quite low in the study, as has been seen in other studies of Asian populations.”