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Randomized Controlled Trial
. 2025 Jan 1;10(1):25-31.
doi: 10.1001/jamacardio.2024.3314.

Coronary Revascularization Guided With Fractional Flow Reserve or Instantaneous Wave-Free Ratio: A 5-Year Follow-Up of the DEFINE FLAIR Randomized Clinical Trial

Javier Escaned  1 , Alejandro Travieso  1 , Hakim-Moulay Dehbi  2 , Sukhjinder S Nijjer  3 , Sayan Sen  3 , Ricardo Petraco  3 , Manesh Patel  4 , Patrick W Serruys  5 , Justin Davies  3 ; DEFINE FLAIR Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Coronary Revascularization Guided With Fractional Flow Reserve or Instantaneous Wave-Free Ratio: A 5-Year Follow-Up of the DEFINE FLAIR Randomized Clinical Trial

Javier Escaned et al. JAMA Cardiol. .

Erratum in

Abstract

Importance: The differences between the use of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) in the long term are unknown.

Objective: To compare long-term outcomes of iFR- and FFR-based strategies to guide revascularization.

Design, setting, and participants: The DEFINE-FLAIR multicenter study randomized patients with coronary artery disease to use either iFR or FFR as a pressure index to guide revascularization. Patients from 5 continents with coronary artery disease and angiographically intermediate severity stenoses who underwent hemodynamic interrogation with pressure wires were included. These data were analyzed from March, 13, 2014, through April, 27, 2021.

Main outcome measures: Five-year major adverse cardiac events (MACE) (a composite of all-cause death, nonfatal myocardial infarction, and unplanned revascularization), as well as the individual components of the combined end point.

Results: At 5 years of follow-up, no significant differences were found between the iFR (mean age [SD], 65.5 [10.8] years; 962 male [77.5%]) and FFR (mean age [SD], 65.2 [10.6] years; 929 male [74.3%]) groups in terms of MACE (21.1% vs 18.4%, respectively; hazard ratio [HR], 1.18; 95% CI, 0.99-1.42; P = .06). While all-cause death was higher among patients randomized to iFR, it was not driven by myocardial infarction (6.3% vs 6.2% in the FFR study arm; HR, 1.01; 95% CI, 0.74-1.38; P = .94) or unplanned revascularization (11.9% vs 12.2% in the FFR group; HR, 0.98; 95% CI, 0.78-1.23; P = .87). Furthermore, patients in whom revascularization was deferred on the basis of iFR or FFR had similar MACE in both study arms (17.9% in the iFR group vs 17.5% in the FFR group; HR, 1.03; 95% CI, 0.79-1.35; P = .80) with similar rates of the components of MACE, including all-cause death. On the contrary, in patients who underwent revascularization after physiologic interrogation, the incidence of MACE was higher in the iFR group (24.6%) compared with the FFR group (19.2%) (HR, 1.36; 95% CI, 1.07-1.72; P = .01).

Conclusions and relevance: At 5-year follow up, an iFR based-strategy was not statistically different than an FFR strategy to guide revascularization in terms of MACE, nonfatal myocardial infarction, and unplanned revascularization.

Trial registration: ClinicalTrials.gov Identifier: NCT02053038.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Escaned reported grants from Philips, Abbott, and Boston Scientific outside the submitted work. Dr Travieso reported grants from Philips and Fundación Alfonso Martín Escudero outside the submitted work. Dr Nijjer reported personal fees from Philips during the conduct of the study and personal fees from Pfizer, AstraZeneca, Bayer, Boehringer Ingelheim, and Amarin outside the submitted work. Dr Sen reported personal fees from Philips during the conduct of the study and personal fees from Medtronic outside the submitted work. Dr Petraco reported personal fees from Philips during the conduct of the study. Dr Patel reported grants from Heartflow and Phillips during the conduct of the study and grants from Novartis, Medtronic, Bayer, and the National Heart, Lung, and Blood Institute, and personal fees from Bayer and Janssen outside the submitted work. Dr Serruys reported consultant fees from SMT, Novartis, Merillife, Philips, and Xeltis outside the submitted work. No other disclosures were reported.

Comment in

References

    1. Escaned J, Berry C, De Bruyne B, et al. Applied coronary physiology for planning and guidance of percutaneous coronary interventions. a clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology. EuroIntervention. 2023. 21;19(6):464-481. doi: 10.4244/EIJ-D-23-00194 - DOI - PMC - PubMed
    1. Pijls NHJ, van Son JAM, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation. 1993;87(4):1354-1367. doi: 10.1161/01.CIR.87.4.1354 - DOI - PubMed
    1. Sen S, Escaned J, Malik IS, et al. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (Adenosine Vasodilator Independent Stenosis Evaluation) study. J Am Coll Cardiol. 2012;59(15):1392-1402. doi: 10.1016/j.jacc.2011.11.003 - DOI - PubMed
    1. Davies JE, Sen S, Dehbi HM, et al. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI. N Engl J Med. 2017;376(19):1824-1834. doi: 10.1056/NEJMoa1700445 - DOI - PubMed
    1. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. ; ESC Scientific Document Group . 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165. doi: 10.1093/eurheartj/ehy394 - DOI - PubMed

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