PCI Improves Angina, QOL in Stable CHD With 'Gray Zone' FFR

Neil Osterweil

May 24, 2018

PARIS — The value of percutaneous coronary intervention (PCI) in patients with stable coronary heart disease (CHD) and gray-zone fractional flow reserve values became a little less gray with the finding that PCI added to optimal medical therapy was associated with significantly better improvement in angina-related symptoms compared with medical therapy alone, new trial results show.

Among 104 patients randomly assigned in the single-center, unblinded, prospective Gray Zone Fractional-Flow Reserve (GZ-FFR) trial to PCI or optimal medical therapy (OMT), patients assigned to receive PCI had less frequent angina (P = .035) and larger improvements in quality-of-life (QoL) measures (P = .012) at 2 months compared with patients assigned to OMT.

In addition, the combination of PCI and OMT was associated with a 50% greater reduction in ischemia on stress MRI and with significant improvements in angina frequency and QoL compared with OMT alone, reported Barry Hennigan, MD, from the University of Glasgow, United Kingdom.

"The treatment effect with PCI plus a mean of 1.3 antianginal drugs in the PCI arm was greater than the ORBITA placebo effect plus a mean of 2.9 antianginal drugs, but we must bear in mind that our PCI arm was not blinded to the treatment," he said here at the Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018.

"Of course, the greatest quality-of-life improvement that we saw in our patients was with those patients that had MRI-defined ischemia," he added.

The objective of the GZ-FFR study was to define the prevalence of major ischemia by MRI and invasive flow assessment and to determine whether deferral of PCI is appropriate in patients with stable CHD and "gray zone" FFR values of 0.75 to 0.82, where the optimal treatment strategy has not been clear.

The randomization was stratified by diabetes status, age, and sex. All patients received guideline-based OMT. The primary endpoint was the delta score at 3 months for the five components of the Seattle Angina Questionnaire (SAQ). The trial had 80% power at the 5% level of significance for a 10-point difference in the SAQ between PCI plus OMT or OMT only.

Patients attending the catheterization lab who had a single 30% to 80% stenosis lesion were eligible for inclusion, and if they had no exclusion criteria (any other PCI targets at the time of randomization, left main artery disease, recent ST-elevation myocardial infarction, or unstable angina) had a clinically indicated standard-of-care FFR assessment, and if the FFR was in the 0.75 to 0.82 range they were eligible for a ComboWire (Philips) assessment of pressure and flow.

Following the ComboWire assessment, patients underwent 3-T stress perfusion MRI and were then randomly assigned to either PCI plus OMT or OMT alone. The PCI group had repeat MRI perfusion at 1 to 2 months, and all patients had follow-up visits at 3 months and 1 year.

Patients in the OMT group were permitted to cross over to the PCI group if doing so was clinically indicated.

Patients in the OMT-only group had improvements at 3 months in the physical limitation, anginal frequency, and QoL domains, with delta scores of 10.55, 9.39, and 10.54, respectively. 

In the PCI group, patients had improvements in physical limitation (16.13), anginal frequency (20.58), QoL (24.04), and treatment satisfaction (1.80).

As noted above, the between-group differences significantly favored PCI for the domains of angina frequency and QoL. 

Hennigan noted that in an informal comparison with the ORBITA trial, which compared FFR-guided PCI with a sham procedure, patients in the GZ-FFR PCI group had significantly better anginal frequency and physical limitation scores than patients in the ORBITA placebo group. He emphasized, however, that patients in the GZ-FFR study knew they were receiving PCI, whereas patients in ORBITA were blinded to treatment assignment.

He acknowledged that the study was limited by being confined to a single center and by difficulty in accruing patients because all had to consent to surgery before randomization. As a result, only 1 of every 40 patients screened was actually recruited into the study.

In addition, the follow-up in GZ-FFR is shorter than that in ORBITA, and there was no sham-procedure control group.

Invited discussant Emanuele Barbato, MD, PhD, from the Cardiovascular Center OLV Aalst in Aalst, Belgium, said that the trial was "very well conducted and sophisticated," but he had some questions about FFR values and possible treatment benefits derived from revascularization.

He questioned how clinicians can determine the pivot point between the clinical benefits that could be anticipated for revascularization and those that could be anticipated from medical therapy, suggesting that the location of lesions might be one parameter.

Hennigan replied that the study was not sufficiently powered to detect differences in outcomes based on lesion locations, "but I absolutely take your point."

"If the patients have lesion morphology that you're not comfortable with, I think you need to be very careful before you defer [PCI]," he continued. "I think every patient needs to be evaluated in a specific nature, taking into account your physiology, your lesion morphology, your clinical characteristics if you have noninvasive testing, and make a decision based on that."

"Very, very interesting study, and a lot of data in it also for practical aspects," commented Andreas Baumbach, MD, from the University of Bristol, United Kingdom, an invited discussant.

He asked whether Hennigan had recommendations for the best way to get patients out of the gray zone, and whether any of the study findings could be incorporated into clinical practice.

"We were worried about caffeine antagonism, so we actually prospectively changed our patient information to avoid caffeine and caffeinated drinks before attending the cath lab to remove that issue, but we also administered high-dose adenosine, because that's thought to overcome that antagonism," Hennigan said.

The study was funded by the British Heart Foundation. Hennigan and coauthors reported having no relevant conflicts of interest. Baumbach and Barbato reported no conflicts of interest relevant to the study.

Congress of the European Association of Percutaneous Coronary Intervention (EuroPCR) 2018. Late-breaking abstract. Presented May 22, 2018.

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