Modest Benefit of PCI Over Medical Therapy in Patients With ‘Grey Zone’ FFR Lesions

PARIS, France—For stable coronary artery disease patients caught in physiology-test purgatory—where an assessment of fractional flow reserve (FFR) provides no clear clinical direction—PCI modestly improves angina symptoms and quality of life, according to the results of a new study.

In a group of patients with stable CAD and FFR values falling between 0.75 and 0.82, which is “borderline” for identifying physiologically significant lesions, PCI plus optimal medical therapy improved two of five domains on the Seattle Angina Questionnaire (SAQ), specifically angina frequency and health-related quality of life, when compared with medical therapy alone.

Additionally, coronary revascularization also appeared to reduce ischemia as assessed by MRI, report investigators.

Of note, the comparison was not blinded and there was no sham procedure in the medical therapy arm.

Speaking at EuroPCR 2018, lead investigator Barry Hennigan, MD (Mater Private Hospital, Cork, Ireland), said that when faced with stable patients who fall within this FFR “grey zone,” treatment with PCI or optimal medical therapy will depend on individual patient characteristics. “I’ll be totally honest, in my clinical practice I would tend to go ahead with PCI if it was technically feasible and safe to do so,” said Hennigan.

Ultimately, though, deciding on the optimal treatment course in patients with borderline FFR results means personalized care. “Clinical judgement at every stage,” he told TCTMD. “You have to interpret the full constellation of symptoms and all the information at your disposal. Personally, I am biased toward treating these patients if I’m convinced by their anginal history and particularly if I'm worried about their lesion morphology.”    

Personally, I am biased toward treating these patients if I’m convinced by their anginal history and particularly if I'm worried about their lesion morphology. Barry Hennigan

Spencer King III, MD (Emory University, Atlanta, GA), who moderated the late-breaking clinical trials session, said patients with a borderline FFR are frequently encountered in clinical practice. “You only do FFR when you’re in doubt,” he told TCTMD. “You don’t do it when you’re absolutely certain. And when you’re in doubt on the angiogram, and you do FFR to see if it’s above or below 0.80, you usually end up with an FFR that is 0.80.”

Complicated Study Protocol

The study, which is known as Grey-Zone FFR (^GZFFR), included patients with single-vessel coronary artery disease (ranging from 30% to 80% diameter stenosis) and an FFR value of 0.75 to 0.82. Upon the completion of the physiologic assessment, patients with borderline FFR values were first taken from the cath lab table to undergo stress perfusion MRI. Only once the MRI assessment was completed were patients randomized to medical therapy or PCI.

For the primary endpoint, which was the difference in SAQ scores at 3 months, angina frequency and quality of life—two of the five SAQ measures studied—were improved to a statistically greater degree with PCI compared with medical therapy. Both groups saw improvements in the SAQ measure of physical limitation, but there was no statistically significant difference between the two treatments. Anginal stability and treatment satisfaction either declined or did not improve meaningfully in either group.

Regarding the stress perfusion MRI data, Hennigan reported that 17.4% of patients had major ischemia and 24.4% had ischemia in any cardiac territory prior to treatment. In follow-up of the PCI-treated patients, ischemia was reduced, with major ischemia observed in just 7.3% of patients and ischemia in any territory observed in 12.2%.

In a post hoc analysis, the ^GZFFR researchers found that the majority patients with ischemia on stress MRI who underwent PCI had an improvement in SAQ quality-of-life scores. In contrast, just 53% of those without ischemia on MRI who underwent PCI had an improvement in quality of life. Although the numbers are small and should be interpreted with care, these data “suggest that when you target ischemia and treat it with PCI patients do better,” said Hennigan.   

Stacking Up Against ORBITA

Given the intense interest in ORBITA—a sham-controlled study that shook up interventional cardiology when investigators failed to show that PCI improved patient symptoms over and above the improvement seen with medical therapy—Hennigan and colleagues compared changes in the SAQ with those observed in ORBITA. According to their analysis, physical-limitation and anginal-frequency scores improved among PCI-treated patients in the ^GZFFR study to a greater extent than was observed among those in the sham-controlled arm of ORBITA. 

“However, we must bear in mind that our PCI group knew that they had received PCI,” said Hennigan. “There was no blinding in our group, so it must be interpreted with caution.”

Discussing the study results following their presentation during a late-breaking clinical trials session yesterday, King said he wouldn’t have expected a dramatic reduction in angina symptoms and other SAQ domains given the type of patients included in the trial. FFR, King pointed out, is just one tool used when contemplating coronary revascularization or medical therapy, and even a borderline FFR value helps inform treatment decisions when used in conjunction with other patient and lesion characteristics. He added that if interventional cardiologists are inclined to treat patients with an FFR between 0.75 and 0.82, this suggests “it isn’t much of a grey zone.”

King stressed that FFR is best understood as a continuum, which was recently observed in a new analysis of ORBITA presented during the same late-breaking session. As reported by TCTMD, invasive physiology testing did not predict improvements in exercise time with PCI, but it did track with ischemia such that worse FFR values at baseline were associated with the greatest ischemia reduction following PCI as compared with medical therapy.

Andreas Baumbach, MD (Queen Mary University and Barts Health Center, London, England), one of the moderators during the late-breaking clinical trials session, said the ^GZFFR study provides a lot of information, not only about the FFR grey zone and the use of stenting versus medical therapy. “One thing we’ve learned is that using different ways of assessing ischemia gets you different results,” he told TCTMD.

As for the comparison with ORBITA, both King and Baumbach said it should be interpreted cautiously, noting that any comparisons between trials is fraught with danger, particularly given the lack of a sham intervention in the ^GZFFR trial.

Indeed, speaking with TCTMD last week about the potential impact of other FFR analyses slated for presentation at EuroPCR 2018, ORBITA principal investigator Rasha Al-Lamee, MBBS (Imperial College London, England), stressed that while they’re difficult to conduct, sham-controlled trials represent the most unbiased way of measuring the relative benefits of PCI and medical therapy.

“I think one of the things we've learned a lot about in the last 6 months is the need for placebo control,” she said. “I think people should bear that in mind as they look at other data, because clearly our expectations aren’t quite met in a blinded trial.”