Instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) were equally safe in deferring patients from coronary revascularization, according to a pooled analysis of two randomized trials published Aug. 6 in JACC: Cardiovascular Interventions.
The analysis included 4,486 patients from the DEFINE-FLAIR and iFR-SWEDEHEART studies. All patients in both trials had at least one coronary lesion in which the functional severity was questionable—between 40 and 80 percent stenosis upon visual assessment.
Pre-specified treatment thresholds were 0.89 for iFR and 0.80 for FFR. Procedures were deferred above those values, while either PCI or coronary artery bypass grafting (CABG) was performed below that cutoff.
Overall, 50 percent of patients in the iFR group had revascularization deferred compared to 45 percent in the FFR group. There were no significant difference in baseline characteristics between the iFR and FFR groups.
Despite a higher deferral rate for iFR, about 4 percent of patients in both groups experienced major adverse cardiac events (MACE) over the ensuing year. The primary composite endpoint consisted of all-cause mortality, heart attack or unplanned revascularization.
“Both studies consistently demonstrated that fewer stenoses were deemed hemodynamically significant when iFR was used,” wrote lead author Javier Escaned, MD, PhD, and colleagues. “As this implies a higher rate of PCI deferral when iFR is used as a diagnostic tool, comparing the outcomes of patients who had iFR or FFR determined PCI deferral is an objective of the utmost clinical importance.”
The researchers noted the one-year event rates for deferred patients in their analysis were about half of those reported in the DEFER trial (8 percent) published in 2001, “reflecting the evolution of interventional and medical therapy.”
Another important finding from DEFINE-FLAIR and iFR-SWEDEHEART was the greater likelihood that individuals deferred for revascularization with acute coronary syndrome (ACS) would experience adverse events. Compared to ACS, those with stable angina had an adjusted 39 percent reduced risk of MACE at one year. MACE rates were 5.91 percent in deferred patients with ACS versus 3.64 percent in those with stable angina.
Unplanned coronary revascularization was the primary driver of the higher event rates in ACS, although death and myocardial infarction also contributed.
“The excess of risk for physiology-based stenosis deferral in patients with ACS may reflect the substantially different physiological conditions found in these patients from those in patients with SAP (stable angina pectoris),” Escaned et al. wrote. “Although FFR has been extensively validated as a clinical tool in patients with SAP, its value in patients with ACS is less well described. Microcirculatory vasodilation during hyperemia can be transiently blunted in the acute phase of ACS, affecting also myocardial territories remote to those subtended by nonculprit stenoses.”
In the studies, physiological assessment was performed for ACS patients in nonculprit vessels once the culprit lesion had been revascularized.
Commenting in a related editorial, two Spanish cardiologists said it is unclear whether subsequent culprit-lesion issues contributed to the higher MACE rates found with ACS or if the nonculprit lesion that was actually tested was to blame. Among other limitations, they pointed out there was no data on antianginal medication taken during follow-up.
However, Fernando Alfonso, MD, PhD, and Fernando Rivero, MD, noted all the methodological questions “do not undermine the value of this well-designed study … but rather indicate that future research is warranted to get further insights on the relative value of these different physiological indexes.”
Functional assessments of stenosis are especially important in “ambiguous coronary lesions,” they added. “Results of the present study clearly demonstrate that among patients with coronary artery disease and intermediate coronary stenosis, both FFR and iFR are equally valid to defer coronary revascularization.”