Instantaneous wave free ratio vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR

Background and Aims Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038).Methods Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA).Results In total, iFR and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group [n = 1128 (50.0%)] vs. the FFR group [n = 1021 (45.2%); P = .001]. In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI was 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.04; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32].Conclusions Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups. Structured Graphical Abstract Instantaneous wave-free ratio (iFR) is a non-hyperaemic pressure index measured in the wave-free period in diastole. Fractional flow reserve (FFR) is the ratio between mean aortic pressure (Pa) and distal coronary pressure (Pd) during hyperaemia. The increased rate of major adverse cardiovascular events is driven by the higher all-cause mortality in the iFR arm. The pooled analysis was conducted by digitalizing the Kaplan-Meier curves with the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA). CI, confidence interval; HR, hazard ratio; PCI, percutaneous coronary intervention.

Automated summary

This study conducted a meta-analysis of the 5-year outcomes of iFR-guided and FFR-guided revascularization, revealing an increased all-cause mortality and major adverse cardiovascular events rate in the iFR group.