Comparison of Major Adverse Cardiac Events between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients with or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial

Joo Myung Lee, Ki Hong Choi, Bon-Kwon Koo, Hakim-Moulay Dehbi, Joon-Hyung Doh, Chang-Wook Nam, Eun-Seok Shin, Christopher M. Cook, Rasha Al-Lamee, Ricardo Petraco, Sayan Sen, Iqbal S. Malik, Sukhjinder S. Nijjer, Hernán Mejía-Rentería, Eduardo Alegria-Barrero, Ali Alghamdi, John Altman, S. rgio B. Baptista, Ravinay Bhindi, Waldemar Bojara & 44 others Salvatore Brugaletta, Pedro Canas Silva, Carlo di Mario, Andrejs Erglis, Robert T. Gerber, Olaf Going, Tobias Härle, Farrel Hellig, Ciro Indolfi, Luc Janssens, Allen Jeremias, Rajesh K. Kharbanda, Ahmed Khashaba, Yuetsu Kikuta, Florian Krackhardt, Mika Laine, Sam J. Lehman, Hitoshi Matsuo, Martijin Meuwissen, Giampaolo Niccoli, Jan J. Piek, Flavo Ribichini, Habib Samady, James Sapontis, Arnold H. Seto, Murat Sezer, Andrew S. P. Sharp, Jasvindar Singh, Hiroaki Takashima, Suneel Talwar, Nobuhiro Tanaka, Kare Tang, Eric van Belle, Niels van Royen, Hugo Vinhas, Christiaan J. Vrints, Darren Walters, Hiroyoshi Yokoi, Bruce Samuels, Chris Buller, Manesh R. Patel, Patrick Serruys, Javier Escaned, Justin E. Davies

Research output: Contribution to journalArticleAcademicpeer-review

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. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.
Original languageEnglish
JournalJAMA cardiology
DOIs
Publication statusPublished - 2019

Cite this

Lee, Joo Myung ; Choi, Ki Hong ; Koo, Bon-Kwon ; Dehbi, Hakim-Moulay ; Doh, Joon-Hyung ; Nam, Chang-Wook ; Shin, Eun-Seok ; Cook, Christopher M. ; Al-Lamee, Rasha ; Petraco, Ricardo ; Sen, Sayan ; Malik, Iqbal S. ; Nijjer, Sukhjinder S. ; Mejía-Rentería, Hernán ; Alegria-Barrero, Eduardo ; Alghamdi, Ali ; Altman, John ; Baptista, S. rgio B. ; Bhindi, Ravinay ; Bojara, Waldemar ; Brugaletta, Salvatore ; Silva, Pedro Canas ; di Mario, Carlo ; Erglis, Andrejs ; Gerber, Robert T. ; Going, Olaf ; Härle, Tobias ; Hellig, Farrel ; Indolfi, Ciro ; Janssens, Luc ; Jeremias, Allen ; Kharbanda, Rajesh K. ; Khashaba, Ahmed ; Kikuta, Yuetsu ; Krackhardt, Florian ; Laine, Mika ; Lehman, Sam J. ; Matsuo, Hitoshi ; Meuwissen, Martijin ; Niccoli, Giampaolo ; Piek, Jan J. ; Ribichini, Flavo ; Samady, Habib ; Sapontis, James ; Seto, Arnold H. ; Sezer, Murat ; Sharp, Andrew S. P. ; Singh, Jasvindar ; Takashima, Hiroaki ; Talwar, Suneel ; Tanaka, Nobuhiro ; Tang, Kare ; van Belle, Eric ; van Royen, Niels ; Vinhas, Hugo ; Vrints, Christiaan J. ; Walters, Darren ; Yokoi, Hiroyoshi ; Samuels, Bruce ; Buller, Chris ; Patel, Manesh R. ; Serruys, Patrick ; Escaned, Javier ; Davies, Justin E. / Comparison of Major Adverse Cardiac Events between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients with or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. In: JAMA cardiology. 2019.
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title = "Comparison of Major Adverse Cardiac Events between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients with or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial",
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. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.",
author = "Lee, {Joo Myung} and Choi, {Ki Hong} and Bon-Kwon Koo and Hakim-Moulay Dehbi and Joon-Hyung Doh and Chang-Wook Nam and Eun-Seok Shin and Cook, {Christopher M.} and Rasha Al-Lamee and Ricardo Petraco and Sayan Sen and Malik, {Iqbal S.} and Nijjer, {Sukhjinder S.} and Hern{\'a}n Mej{\'i}a-Renter{\'i}a and Eduardo Alegria-Barrero and Ali Alghamdi and John Altman and Baptista, {S. rgio B.} and Ravinay Bhindi and Waldemar Bojara and Salvatore Brugaletta and Silva, {Pedro Canas} and {di Mario}, Carlo and Andrejs Erglis and Gerber, {Robert T.} and Olaf Going and Tobias H{\"a}rle and Farrel Hellig and Ciro Indolfi and Luc Janssens and Allen Jeremias and Kharbanda, {Rajesh K.} and Ahmed Khashaba and Yuetsu Kikuta and Florian Krackhardt and Mika Laine and Lehman, {Sam J.} and Hitoshi Matsuo and Martijin Meuwissen and Giampaolo Niccoli and Piek, {Jan J.} and Flavo Ribichini and Habib Samady and James Sapontis and Seto, {Arnold H.} and Murat Sezer and Sharp, {Andrew S. P.} and Jasvindar Singh and Hiroaki Takashima and Suneel Talwar and Nobuhiro Tanaka and Kare Tang and {van Belle}, Eric and {van Royen}, Niels and Hugo Vinhas and Vrints, {Christiaan J.} and Darren Walters and Hiroyoshi Yokoi and Bruce Samuels and Chris Buller and Patel, {Manesh R.} and Patrick Serruys and Javier Escaned and Davies, {Justin E.}",
year = "2019",
doi = "10.1001/jamacardio.2019.2298",
language = "English",
journal = "JAMA cardiology",
issn = "2380-6583",
publisher = "American Medical Association",

}

Lee, JM, Choi, KH, Koo, B-K, Dehbi, H-M, Doh, J-H, Nam, C-W, Shin, E-S, Cook, CM, Al-Lamee, R, Petraco, R, Sen, S, Malik, IS, Nijjer, SS, Mejía-Rentería, H, Alegria-Barrero, E, Alghamdi, A, Altman, J, Baptista, SRB, Bhindi, R, Bojara, W, Brugaletta, S, Silva, PC, di Mario, C, Erglis, A, Gerber, RT, Going, O, Härle, T, Hellig, F, Indolfi, C, Janssens, L, Jeremias, A, Kharbanda, RK, Khashaba, A, Kikuta, Y, Krackhardt, F, Laine, M, Lehman, SJ, Matsuo, H, Meuwissen, M, Niccoli, G, Piek, JJ, Ribichini, F, Samady, H, Sapontis, J, Seto, AH, Sezer, M, Sharp, ASP, Singh, J, Takashima, H, Talwar, S, Tanaka, N, Tang, K, van Belle, E, van Royen, N, Vinhas, H, Vrints, CJ, Walters, D, Yokoi, H, Samuels, B, Buller, C, Patel, MR, Serruys, P, Escaned, J & Davies, JE 2019, 'Comparison of Major Adverse Cardiac Events between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients with or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial' JAMA cardiology. https://doi.org/10.1001/jamacardio.2019.2298

Comparison of Major Adverse Cardiac Events between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients with or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. / Lee, Joo Myung; Choi, Ki Hong; Koo, Bon-Kwon; Dehbi, Hakim-Moulay; Doh, Joon-Hyung; Nam, Chang-Wook; Shin, Eun-Seok; Cook, Christopher M.; Al-Lamee, Rasha; Petraco, Ricardo; Sen, Sayan; Malik, Iqbal S.; Nijjer, Sukhjinder S.; Mejía-Rentería, Hernán; Alegria-Barrero, Eduardo; Alghamdi, Ali; Altman, John; Baptista, S. rgio B.; Bhindi, Ravinay; Bojara, Waldemar; Brugaletta, Salvatore; Silva, Pedro Canas; di Mario, Carlo; Erglis, Andrejs; Gerber, Robert T.; Going, Olaf; Härle, Tobias; Hellig, Farrel; Indolfi, Ciro; Janssens, Luc; Jeremias, Allen; Kharbanda, Rajesh K.; Khashaba, Ahmed; Kikuta, Yuetsu; Krackhardt, Florian; Laine, Mika; Lehman, Sam J.; Matsuo, Hitoshi; Meuwissen, Martijin; Niccoli, Giampaolo; Piek, Jan J.; Ribichini, Flavo; Samady, Habib; Sapontis, James; Seto, Arnold H.; Sezer, Murat; Sharp, Andrew S. P.; Singh, Jasvindar; Takashima, Hiroaki; Talwar, Suneel; Tanaka, Nobuhiro; Tang, Kare; van Belle, Eric; van Royen, Niels; Vinhas, Hugo; Vrints, Christiaan J.; Walters, Darren; Yokoi, Hiroyoshi; Samuels, Bruce; Buller, Chris; Patel, Manesh R.; Serruys, Patrick; Escaned, Javier; Davies, Justin E.

In: JAMA cardiology, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Comparison of Major Adverse Cardiac Events between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients with or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial

AU - Lee, Joo Myung

AU - Choi, Ki Hong

AU - Koo, Bon-Kwon

AU - Dehbi, Hakim-Moulay

AU - Doh, Joon-Hyung

AU - Nam, Chang-Wook

AU - Shin, Eun-Seok

AU - Cook, Christopher M.

AU - Al-Lamee, Rasha

AU - Petraco, Ricardo

AU - Sen, Sayan

AU - Malik, Iqbal S.

AU - Nijjer, Sukhjinder S.

AU - Mejía-Rentería, Hernán

AU - Alegria-Barrero, Eduardo

AU - Alghamdi, Ali

AU - Altman, John

AU - Baptista, S. rgio B.

AU - Bhindi, Ravinay

AU - Bojara, Waldemar

AU - Brugaletta, Salvatore

AU - Silva, Pedro Canas

AU - di Mario, Carlo

AU - Erglis, Andrejs

AU - Gerber, Robert T.

AU - Going, Olaf

AU - Härle, Tobias

AU - Hellig, Farrel

AU - Indolfi, Ciro

AU - Janssens, Luc

AU - Jeremias, Allen

AU - Kharbanda, Rajesh K.

AU - Khashaba, Ahmed

AU - Kikuta, Yuetsu

AU - Krackhardt, Florian

AU - Laine, Mika

AU - Lehman, Sam J.

AU - Matsuo, Hitoshi

AU - Meuwissen, Martijin

AU - Niccoli, Giampaolo

AU - Piek, Jan J.

AU - Ribichini, Flavo

AU - Samady, Habib

AU - Sapontis, James

AU - Seto, Arnold H.

AU - Sezer, Murat

AU - Sharp, Andrew S. P.

AU - Singh, Jasvindar

AU - Takashima, Hiroaki

AU - Talwar, Suneel

AU - Tanaka, Nobuhiro

AU - Tang, Kare

AU - van Belle, Eric

AU - van Royen, Niels

AU - Vinhas, Hugo

AU - Vrints, Christiaan J.

AU - Walters, Darren

AU - Yokoi, Hiroyoshi

AU - Samuels, Bruce

AU - Buller, Chris

AU - Patel, Manesh R.

AU - Serruys, Patrick

AU - Escaned, Javier

AU - Davies, Justin E.

PY - 2019

Y1 - 2019

N2 - 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. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.

AB - 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. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069171751&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31314045

U2 - 10.1001/jamacardio.2019.2298

DO - 10.1001/jamacardio.2019.2298

M3 - Article

JO - JAMA cardiology

JF - JAMA cardiology

SN - 2380-6583

ER -