Clinical Events After Deferral of LAD Revascularization Following Physiological Coronary Assessment

Abstract

Background: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR).

Objectives: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial.

Methods: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex.

Results: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06).

Conclusions: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral.

Keywords: coronary stenosis; fractional flow reserve; instantaneous wave-free ratio.

Graphical abstract

Figure 1

Flow Chart Outlining Patient Selection Patients were included from the DEFINE-FLAIR trial. This analysis was focused on patients who had lesions within their LAD, and who then went on to be deferred on the basis of intracoronary physiology (either iFR or FFR). The total number of patients included in the LAD deferred analysis was 872. DEFINE-FLAIR = Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation; FFR = fractional flow reserve; iFR = instantaneous wave-free ratio; LAD = left anterior descending.

Figure 2

Summary of Clinical Events in LAD-Deferred Patients Bar charts outlining clinical events in patients with LAD stenoses deferred on the basis of intracoronary physiology. The orange bars denote patients whose treatment was guided by iFR, and the blue bars denote patients whose treatment was guided by FFR. iFR-guided deferral was associated with significantly lower rates of unplanned revascularization (right, p = 0.03). This was driven by numerically greater rates of target vessel revascularization with FFR (p = 0.06). iFR-guided deferral was associated with numerically lower rates of myocardial infarction (MI) (left, p = 0.06). This was driven by numerically greater rates of target vessel MI with FFR (p = 0.08). There was no difference in periprocedural MI (p = 1.00). Abbreviations as in Figure 1.

Central Illustration

Major Adverse Cardiac Events in Left Anterior Descending–Deferred Patients: Kaplan-Meier Curves This figure outlines the primary endpoint in patients with left anterior descending stenoses who were deferred according intracoronary physiology. Major adverse cardiac events were defined as the composite of cardiovascular death, myocardial infarction, and unplanned revascularization. The solid blue line denotes the fractional flow reserve arm, and the dashed orange line denotes the instantaneous wave-free ratio arm. Instantaneous wave-free ratio–guided deferral was associated with a significantly lower major adverse cardiac events rate (adjusted hazard ratio: 0.46; 95% confidence interval: 0.22 to 0.95; p = 0.04).

Figure 3

Kaplan-Meier for MACE in Non-LAD Patients Primary endpoint in patients with non-LAD stenoses who were deferred according to intracoronary physiology. MACE was defined as the composite of cardiovascular death, myocardial infarction, and unplanned revascularization. The solid blue line denotes the FFR arm, and the dashed orange line denotes the iFR arm. There was no difference in the MACE rate between iFR- and FFR-guided deferral (adjusted hazard ratio: 1.18; 95% confidence interval: 0.59 to 2.38; p = 0.63). Abbreviations as in Figure 1.