PARIS – Patients with stable angina and a fractional flow reserve (FFR) value in the grey zone of 0.75-0.81 experienced a significant reduction in myocardial ischemia and substantially greater quality of life improvement if they were randomized to percutaneous coronary intervention (PCI) plus optimal medical therapy than to optimal medical therapy alone in the Scottish Grey-zone FFR Study.
Thewas a single-center, prospective, unblinded, randomized trial that included 100 patients with stable angina, single-vessel disease, and a fractional flow reserve in the grey zone of 0.75-0.81. While broad consensus exists that an FFR below 0.75 constitutes evidence of a hemodynamically significant coronary lesion warranting revascularization and an FFR greater than 0.80 indicates a lesion isn’t functionally significant and therefore PCI can safely be deferred, there has been uncertainty on what to do about lesions in the grey zone, which are frequently encountered in the cardiac catheterization laboratory.
“In my clinical practice, I tend to go ahead with PCI for patients in the grey zone if I felt it was clinically feasible and safe to do so, particularly if I was worried about their lesion morphology,”, said in response to questions after presenting the results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions. “If it’s a proximal LAD [left anterior descending artery] lesion and it’s a grey zone patient, particularly if it’s a lesion morphology that you’re not comfortable with, I think you need to be very careful before you defer a case.”
The twin purposes of the Scottish study were to define the prevalence of major ischemia by stress MRI and invasive flow assessment via a pressure wire in grey zone patients – something which hadn’t been done before – and to determine if PCI deferral in such patients is appropriate in terms of symptom control. The primary outcome was change in angina severity at 3 months follow-up using the Seattle Angina Questionnaire (SAQ).
Scores on two of the five domains of the SAQ – anginal frequency and quality of life – were significantly improved in the PCI group. Anginal frequency scores improved by a mean of 20.58 points in the PCI plus optimal medical therapy (OMT) group, compared with a 9.39-point improvement with OMT alone. Quality of life scores improved by 24.04 points in the PCI group versus 9.39 points in controls, said Dr. Hennigan, an interventional cardiologist at the University of Glasgow and Golden Jubilee National Hospital. Scores in the other three SAQ domains – physical limitations, anginal stability, and treatment satisfaction – didn’t differ significantly between the two study arms, although consistently greater improvements were seen in the PCI group.
Baseline stress perfusion MRI as assessed by two blinded observers demonstrated that 17.4% of patients with stable angina and a grey zone FFR had major ischemia, while any ischemia – major or minor – was present in 24.4%. Follow-up scans at 3 months showed a roughly 50% reduction in the prevalence of ischemia in the PCI group, with 7.3% of treated patients still having major ischemia and 12.2% having any ischemia.
Also, 28% of participants had evidence of ischemia at baseline based upon their coronary flow reserve measurements and 8% had a hyperemic stenosis resistance measurement indicative of ischemia. So the FFR grey zone encompasses a range of cardiovascular risks.
In the PCI plus OMT group, 89% of patients (eight of nine) with baseline ischemia on stress MRI had a greater than 10-point improvement in quality of life scores on the SAQ at follow-up in contrast to 53% of patients without ischemia, which made for a statistically significant difference. An improvement of that magnitude is generally considered clinically meaningful. In contrast, in the OMT-only group, 9 of 14 patients with baseline ischemia (64.2%) had a greater than 10-point quality of life improvement, which wasn’t significantly different from the 45.5% improvement rate in patients with no ischemia.
The lessons? Grey zone patients who benefit most from prompt revascularization are those with demonstrable ischemia. In addition, roughly half of grey zone patients with stable angina will improve their quality of life scores by more than 10 points with OMT alone regardless of the presence of myocardial ischemia or not.
Dr. Hennigan was repeatedly asked how he reconciles the results of the grey zone study with those of the much-discussedtrial, the first and only randomized trial of real versus sham PCI in patients with stable angina. ORBITA didn’t find a significant quality of life advantage for real PCI over sham PCI.
“It is quite possible that a lot of the effect that we saw in our PCI group was placebo related,” he conceded. “However, we do have objective evidence that we reduced ischemia on MRI. Also, 29% of ORBITA patients had an FFR above 0.8, whereas nearly all our patients were below that threshold. So we perhaps had more prevalent ischemia than the ORBITA cohort.”
Also informative is a comparison of SAQ scores at follow-up in the sham PCI ORBITA control group versus the grey zone Scottish PCI group, Dr. Hennigan continued. The Scottish PCI group had a mean 20.6-point improvement in anginal frequency scores while on an average of 1.3 antianginal medications, compared with a 9.6-point improvement in ORBITA patients on 2.9 drugs. The grey zone group who got PCI plus OMT also had a mean 16.1-point improvement in the SAQ physical limitations domain, versus a 5.0-point improvement in the ORBITA controls.
The Grey-zone FFR Study was supported by the British Heart Foundation. Dr. Hennigan reported having no financial conflicts of interest.