Deferring revascularization in LAD deemed safe with iFR

Instantaneous wave-free ratio (iFR) can safely guide revascularization decisions in left anterior descending (LAD) arteries with moderate stenosis, according to an analysis of the DEFINE-FLAIR study published in the Journal of the American College of Cardiology. In fact, patients whose lesions were deferred on the basis of iFR were significantly less likely to experience major adverse cardiovascular events (MACE) compared to those who were deferred through fractional flow reserve (FFR).

Both forms of physiological assessment have proven effective in guiding percutaneous coronary intervention (PCI) decisions in previous trials, but clinicians are hesitant to leave the LAD unstented “because the LAD often supplies a large territory of myocardium,” wrote lead author Sayan Sen, PhD, with Imperial College London, and colleagues.

For their post hoc analysis of DEFINE-FLAIR, Sen et al. studied one-year MACE rates—a composite of MI, cardiovascular death and unplanned revascularization—among 872 patients who had LAD lesions deferred based on an iFR above 0.89 or an FFR above 0.80. Patients received PCI if their values were below those thresholds.

All patients had moderate stenosis between 40 and 70 percent upon angiographic assessment, and about half of the participants had revascularization deferred through each physiological assessment.

Overall, MACE occurred in 2.44 percent of patients in the iFR group and 5.26 percent in the FFR group—a relative reduction of 54 percent when the outcomes were adjusted for the age and sex of participants. The difference was driven by a significantly lower rate of unplanned revascularization (2.22 percent versus 4.9 percent) as well as a numerically lower incidence of MI (0.44 percent versus 2.14 percent) over the one year of follow-up.  

“This analysis suggests that, for patients having LAD lesions deferred based on physiology, the event rate is not higher than that of patients in which non-LAD lesions are deferred,” Sen and colleagues wrote. “Furthermore, there is no sign of increased risk if guided by iFR compared with those guided by FFR. This suggests that hyperemia is not required to safely defer lesions in the left anterior descending artery.”

The researchers said in the original DEFINE-FLAIR study, which included both LAD and non-LAD lesions, MACE rates were similar after deferral with iFR or FFR. But the initial trial used all-cause mortality instead of cardiovascular mortality as part of the composite primary endpoint—a tweak that shouldn’t be ignored, according to the authors of a related editorial.

“Rather unusually, and without any explanation, the primary endpoint in this study was different from the endpoint used in the parent trial,” Amir Ahmadi, MD, with the University of British Columbia in Vancouver and Icahn School of Medicine at Mount Sinai in New York, and colleagues wrote.

“This is of particular concern, because a strategy of applying the original DEFINE-FLAIR primary endpoint to the present dataset revealed that there was no statistically significant difference in risk between the iFR and FFR deferral groups.”

Still, Sen and coauthors wrote their results “should be considered hypothesis-generating” but also “confirm there is no safety hazard for using iFR to defer lesions in the LAD.”

In their editorial, Ahmadi and co-authors said cost and time constraints may prevent broad uptake of intracoronary, physiology-guided strategies to manage patients with stable ischemic heart disease (SIHD). But less invasive blood flow modeling methods might perform just as well and be more easily integrated into clinical practice, they wrote.

“If the longer-term follow-up for iFR and FFR based on coronary angiography or computed tomography continue to be promising, we may have several convenient modalities of risk assessment and algorithms for candidacy for coronary revascularization in SIHD,” Ahmadi et al. wrote. “These techniques may be complementary to each other; for example, one that can be used noninvasively as a true gatekeeper to the catheterization laboratory, and another that can be used in the laboratory more efficiently than FFR, without the need for vasodilation.”