FFR Values Linked to Quality-of-Life Improvement After PCI in Stable CAD Patients
In an analysis of FAME 1 and 2, patients with the lowest FFR values before PCI had the most to gain.
Measuring fractional flow reserve (FFR) may help identify patients with stable CAD who will reap the greatest gains in quality of life after PCI, an analysis of the FAME 1 and 2 trials shows.
In those studies, patients with the lowest baseline FFR values and the biggest changes in FFR from before to after the procedure—as well as those with more severe Canadian Cardiovascular Society angina symptoms—had the most substantial improvements in quality of life measured at 1 month and 1 year after PCI, according to a study published online September 18, 2018, ahead of print in Circulation.
The findings are particularly relevant given the results of the ORBITA trial, which cast doubt on the benefit of PCI in patients with stable angina, senior author William Fearon, MD (Stanford University School of Medicine, CA), told TCTMD.
“We were particularly interested in trying to further understand the relationship between fractional flow reserve and angina relief, and thought that this would be a way of understanding the benefit of PCI and doing it in a way that removed any potential bias due to lack of blinding of the patients,” he said.
“I think by showing that there was this really clear relationship between how abnormal the FFR was—or how great a degree of ischemia there was—and the benefit of angina relief and quality of life helps to demonstrate that PCI does, in fact, have a positive effect on relieving symptoms and improving quality of life,” Fearon concluded.
For the study, Fearon along with lead author Takeshi Nishi, MD (Stanford University School of Medicine), and colleagues, looked at data from the FAME 1 and FAME 2 trials on 716 stable patients who had at least one lesion with an FFR value of 0.80 or lower that was treated with PCI and a reference group of 185 medically treated patients who had CAD but no lesions with abnormal FFR values.
Patients in the FFR-guided PCI group were divided into tertiles according to their baseline FFR values:
- Upper (0.80 to 0.70)
- Middle (0.69 to 0.51)
- Lower (≤ 0.50)
At baseline, quality of life—assessed using the European Quality of Life-5 Dimensions (EQ-5D)—was similar across the three FFR tertiles and the reference group. After PCI, quality of life remained unchanged in the reference patients, but improved in all three FFR groups. Patients with the lowest baseline FFR values saw the largest gains in quality of life at 1 month and 1 year.
A similar pattern was seen when patients who underwent FFR-guided PCI were divided into three groups based on the degree of change in FFR from before to after the procedure; those with the biggest change—of at least 0.33—had the greatest improvement in quality of life.
Use of mixed-effects models for repeated measures revealed that a lower baseline FFR, a greater change in FFR, and a higher angina class were all associated with a more substantial gain in quality of life at both 1 month and 1 year.
The link between FFR and improvements in quality of life “is biologically plausible in that myocardial ischemia with angina caused by obstructive CAD reduces functional capacity, leading to a decreased activity level and quality-of-life impairment,” the authors write. “Treating obstructive CAD which is responsible for ischemia should relieve angina, restore functional capacity, and improve quality of life. The current study demonstrates that measuring FFR can identify patients whose quality of life will improve the greatest with PCI.”
ORBITA Spurs Doubts
Nishi et al acknowledge, however, that ORBITA “raised questions about this paradigm by showing no significant difference in angina or quality of life after PCI at 6-week follow-up.”
But the main limitation of ORBITA, they say, is that FFR—though measured—was not used to guide PCI, as it was in the FAME trials.
“Approximately one-third of the lesions treated with PCI in ORBITA had FFR values > 0.80, which we know from previous studies do not benefit from PCI; patients with functionally nonsignificant CAD do just as well, if not better when treated medically,” the researchers say. “Treating these nonsignificant lesions with PCI only dilutes the benefit of PCI.”
Moreover, they note, ORBITA included patients with single-vessel disease only (the FAME studies enrolled patients with either single- or multivessel disease) and had a smaller sample size.
“As quality of life has a wide between-individual variability and multifactorial nature, a larger sample size might be required to identify the relationship between quality-of-life improvement and the degree of ischemia measured by invasive physiology,” the authors write.
Fearon pointed out that FAME 2 was criticized for not using a sham control, so patients in the medical therapy arm knew they had a significant, but untreated, lesion.
“If the benefit of PCI was just a placebo effect, then every patient should have improved to a similar degree with respect to their angina relief and quality of life, but we didn’t see that,” he said. “We saw this distinct relationship, the lower the FFR or the greater the change in FFR, the greater the benefit, which implies that there is a pathophysiologic mechanism that’s being relieved with PCI that’s improving symptoms and improving quality of life and that FFR helps identify those patients who will benefit the most.”
The results of this study and the 5-year follow-up of FAME 2, which showed that FFR-guided PCI reduced risks of MI and the composite of death, MI, or urgent revascularization, Fearon said, “show that by measuring FFR you can identify patients and lesions that will benefit from PCI. That will lead to not only improved angina relief and quality of life, but also [fewer] harder endpoints in the long term.”
Nishi T, Piroth Z, De Bruyne B, et al. Fractional flow reserve and quality-of-life improvement after percutaneous coronary intervention in patients with stable coronary artery disease. Circulation. 2018;Epub ahead of print.
- FAME 1 was supported by Radi Medical Systems, Stichting Vrienden van het Hart Zuidoost Brabant, and Medtronic. FAME 2 was supported by St. Jude Medical.
- Fearon reports receiving institutional research support from Medtronic, Abbott Vascular, ACIST Medical, CathWorks, and Edwards LifeSciences; and having a consulting relationship with Boston Scientific and HeartFlow.
- Nishi reports no relevant conflicts of interest.