Operators should continue to use the fractional flow reserve (FFR) cutoff of ≤0.8 in deciding to revascularize a lesion, even with an intact coronary flow reserve (CFR) >2.That is the take-home message from the DEFINE-FLOW observational study, presented Friday at the TCT Connect virtual conference.
These findings were presented Friday by Nils Johnson, MD, MS, of McGovern Medical School at UT Health (Houston) and Memorial Hermann Hospital – Texas Medical Center.
The role of coronary flow reserve (CFR) for invasive assessment of coronary lesions currently remains unclear since fractional flow reserve (FFR) has become a reference standard (≤0.80) decision for revascularization. Prior data have indicated that lesions with intact CFR (≥2) do well; but there have not been any larger studies looking at outcomes based on simultaneous assessment by both FFR and CFR. Investigators of the DEFINE-FLOW study sought to answer this question
This observational study included 455 patients enrolled from 12 sites in six countries. Of those enrolled, 430 patients (533 lesions) were protocol-treated and followed for 2 years.
Stable coronary lesions underwent simultaneous FFR and CFR measurement in at least duplicate with central core lab review of the tracings. Treatment followed the local measurements according to a uniform protocol whereby only lesions with both FFR ≤0.8 (termed FFR+) and CFR <2 (CFR+) underwent PCI. All other combinations, including FFR ≤0.8 but intact CFR >2.0 (termed CFR-), received initial medical therapy. FFR >0.8 was termed FFR-.
The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction, and any revascularization at 2 years with a non-inferiority margin of 10%.
The study findings for MACE were 5.8% for FFR-/CFR-, 10.8% for FFR+/CFR-, 12.4% for FFR-/CFR+, and 14.4% for FFR+/CFR+ (after PCI). The difference between FFR+/CFR- and FFR-/CFR- was 5.0% (95% confidence interval, -1.5% to +11.5%; p = 0.065 for non-inferiority). Therefore, the study found that vessels with abnormal FFR ≤0.8 but intact CFR ≥2 did not have non-inferior outcomes compared to FFR >0.8 and CFR ≥2 when treated medically.
In a news conference Thursday, K. Lance Gould, MD, of the University of Texas Medical School, Houston, explained to reporters the study failed to prove its hypothesis, which was that vessels with abnormal FFR (≤0.8) but intact CFR (≥2) would show noninferior outcomes to vessels showing intact readings on both measures (FFR >8 and CFR ≥2) when treated medically.
In fact, the FFR+/CFR- failed to meet noninferiority, meaning that the FFR cutoff still holds, regardless of the CFR reading, Gould explained.
These findings are interesting but, given the observational nature of the study, they come with limitations.
“There were a number of limitations to this study, such as few lesions with severe FFR/CFR as well as unblinded subjects and physicians,” Johnson said in a news release announcing the study results. “The limitations coupled with the results makes this a hypothesis-generating study that can help to further understand the role of invasive CFR and how to treat CFR/FFR discordance.”
The DEFINE-FLOW trial was funded by Philips (previously Volcano Corporation).