Writing in The New England Journal of Medicine, Deepak L Bhatt (Brigham and Women’s Hospital and Vascular Center and Harvard Medical School, Boston, USA) suggests that instantaneous wave-free ratio (iFR; Philips Volcano) may be the new standard of assessing coronary lesions after two studies indicated that iFR was non-inferior to fractional flow reserve (FFR) with respect to the one-year rate of major adverse cardiac events (MACE). Both studies also found FFR was associated with significantly more procedural-related adverse events than was iFR.
Bhatt made his comments in an accompanying editorial to the two studies—DEFINE-FLAIR (Functional lesion assessment of intermediate stenosis to guide revascularisation) and iFR-SWEDEHEART (iFR versus FFR in patients with stable angina pectoris or acute coronary syndrome)— which were published in The New England Journal Of Medicine to coincide with their presentation (during the same late-breaking session) at the 2017 scientific sessions of the American College of Cardiology (ACC; 17–19 March, Washington, DC, USA).
In their report of the DEFINE-FLAIR trial, Justin Davies (Hammersmith Hospital, Imperial College, London, UK) and others state that “several studies have questioned the need for the administration of a vasodilator to assess stenosis severity”—explaining that a vasodilator, such as adenosine, is typically used to induce maximal hyperaemia (the required state for FFR). Noting that studies have also shown that FFR is not superior to iFR, a pressure-derived index of stenosis severity that does not involve the use of vasodilator, Davies et al state that the purpose of DEFINE-FLAIR was “to determine the efficacy and safety of an iFR-guided strategy vs. an FFR-guided strategy for coronary revascularisation”.
In the study, patients with coronary artery disease and at least one native artery in which the stenosis was of questionable severity (40–70% stenosis on coronary angiography) were randomised to physiological assessment with iFR (1,242) or with FFR (1,250). The threshold for treatment was 0.89 for iFR and 0.80 for FFR; therefore, a stenosis was revascularised—with either percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)—if iFR/FFR measurements were equal or lower than these prespecified thresholds. Treatment was deferred in either group if the iFR/FFR measurements were below these thresholds. The primary endpoint was the one-year risk of MACE; a composite of death, non-fatal myocardial infarction or unplanned revascularisation.
Davies et al report that the number of functionally significant lesions was significantly lower in the iFR group: 451 vs. 557 for FFR; p=0.004. They add: “This difference could be a consequence of dissimilar thresholds for the two measures. In addition, iFR has been shown to be more closely linked to coronary flow reserve than FFR, and a previous study has shown higher revascularisation rates associated with assessment guided by FFR than with assessment guided by coronary flow reserve.” However, despite this result, there were no significant differences in the rate of the primary outcome (MACE at one year) between groups: 6.8% for iFR vs. 7% for FFR (p=0.78).
Furthermore, iFR was associated with fewer adverse procedural signs or symptoms than was FFR—3.1% vs. 30.8%, respectively; p<0.001. “Although adenosine is a generally safe drug that is used in millions of diagnostic procedures annually, its risks are well documented and it is not suitable for every patient; therefore, avoiding the use of adenosine is preferable,” Davies et al comment. They also note that adenosine “contributes substantially” to the cost of physiological assessment. In his editorial, Bhatt reports that the use of FFR remains low “despite strong data in its favour” and says that a “major reason” for this low usage is the need for a vasodilator during FFR.
According to Davies et al, their results suggest that iFR alone can “effectively identify stenoses that require intervention” and also provide “clinical evidence that there is no significant advantage to the administration of a hyperaemic agent.” Prior to the results of DEFINE-FLAIR, a hybrid iFR-FFR approach had been proposed in which iFR was used as the initial measurement and FFR used if a stenosis had iFR-intermediate severity.
The results of the iFR-SWEDEHEART were similar to those of DEFINE-FLAIR. In this study, which used SCAAR (Swedish coronary angiography and angioplasty) registry data for enrolment, 1,019 patients were assigned to iFR and 1,018 were assigned to FFR. Again, there was no significant difference in the primary endpoint—also MACE at 12 months—6.7% for the iFR group vs. 6.1% for the FFR group (p=0.007 for non-inferiority). Furthermore, chest discomfort was reported significantly more frequently in the FFR group than in the iFR group: 68.3% vs. 3% (p<0.001). Authors Matthias Götberg (Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden) conclude: “Among patients with an indication for physiologically guided assessment of coronary-artery stenosis, an iFR-guided revascularisation strategy was found to be non-inferior to an FFR-guided revascularisation strategy with respect to the rate of MACE within 12 months.”
Bhatt, in his editorial, comments that “there will always be patients in the catheterisation laboratory who have a coronary stenosis of intermediate severity on angiography”. “FFR has been the evidence-based standard for invasive evaluation of such lesions, but it now appears that iFR may be the new standard,” he adds.
Davies told Cardiovascular News that a full cost analysis that compared iFR with FFR would be coming out later this year, which he said was “likely to be skewed strongly towards iFR”. He adds that if iFR became the standard approach for physiological assessment, it may led to physiological assessment being more widely used in clinical practice. “Anything you can do to ease the burden of an assessment will increase adoption. So, we hope, that this will be the case with coronary physiology using more iFR,” Davies explains.