|dc.description.abstract||IMPORTANCE Invasive physiologic indices such as fractional flow reserve (FFR) and
instantaneous wave-free ratio (iFR) are used in clinical practice. Nevertheless, comparative
prognostic outcomes of iFR-guided and FFR-guided treatment in patients with type 2
diabetes have not yet been fully investigated.
OBJECTIVE To compare 1-year clinical outcomes of iFR-guided or FFR-guided treatment in
patients with and without diabetes in the Functional Lesion Assessment of Intermediate
Stenosis to Guide Revascularization (DEFINE-FLAIR) trial.
DESIGN, SETTING, AND PARTICIPANTS The DEFINE-FLAIR trial is a multicenter, international,
randomized, double-blinded trial that randomly assigned 2492 patients in a 1:1 ratio to undergo
either iFR-guided or FFR-guided coronary revascularization. Patients were eligible for trial
inclusion if they had intermediate coronary artery disease (40%-70% diameter stenosis) in at
least 1 native coronary artery. Data were analyzed between January 2014 and December 2015.
INTERVENTIONS According to the study protocol, iFR of 0.89 or less and FFR of 0.80 or less
were used as criteria for revascularization. When iFR or FFR was higher than the prespecified
threshold, revascularization was deferred.
MAIN OUTCOMES AND MEASURES The primary end point was major adverse cardiac events
(MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or
unplanned revascularization at 1 year. The incidence of MACE was compared according to the
presence of diabetes in iFR-guided and FFR-guided groups.
RESULTS Among the total trial population (2492 patients), 758 patients (30.4%) had diabetes.
Mean age of the patients was 66 years, 76% were men (1868 of 2465), and 80% of patients
presented with stable angina (1983 of 2465). In the nondiabetes population (68.5%; 1707
patients), iFR guidance was associated with a significantly higher rate of deferral of
revascularization than the FFR-guided group (56.5% [n = 477 of 844] vs 46.6% [n = 402
of 863]; P < .001). However, it was not different between the 2 groups in the diabetes population
(42.1% [n = 161 of 382] vs 47.1% [n = 177 of 376]; P = .15). At 1 year, the diabetes population
showed a significantly higher rate of MACE than the nondiabetes population (8.6% vs 5.6%;
adjusted hazard ratio [HR], 1.88; 95% CI, 1.28-2.64; P < .001). However,there was no significant
difference in MACE rates between iFR-guided and FFR-guided groups in both the diabetes
(10.0% vs 7.2%; adjusted HR, 1.33; 95% CI, 0.78-2.25; P = .30) and nondiabetes population
(4.7% vs 6.4%; HR, 0.83; 95% CI, 0.51-1.35; P = .45) (interaction P = .25).
CONCLUSIONS AND RELEVANCE The diabetes population showed significantly higher risk of
MACE than the nondiabetes population, even with the iFR-guided or FFR-guided treatment.
The iFR-guided and FFR-guided treatment showed comparable risk of MACE and provided
equal safety in selecting revascularization target among patients with diabetes.||spa