Clinical trial NCT04379947: Preoperative Use of Fractional Flow Reserve in CABG Use and Effectiveness of FFR-based CABG in Real-life Practice
Official title: A Real Life All-comers Retrospective Study on FFR-based CABG
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Fracational Flow Reserve
Coronary Artery Disease
Coronary Artery Bypass Surgery
Lead sponsor: University of Glasgow
Sponsor class: OTHER
First posted: 2020-05-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be retrospectively included in the study from 1st December 2010 to 31st December 2019. All surgical candidates with at least one intermediate lesion will be included. Patients that received a preoperative FFR evaluation before being referred for CABG will be part of the FFR-CABG group. The rest of the patients will be included in the Angio-CABG group.

Inclusion will be on an "all-comers" basis including both elective and urgent (and urgent in-house) isolated CABG cases. However, patients undergoing emergency revascularization for iatrogenic complications or other conditions that would prevent a careful analysis of angiographic severity of the lesions will be excluded.

Brief summary: The use of fractional flow reserve (FFR) to guide coronary artery bypass graft (CABG) is controversial and not ubiquitously adopted across the units. There is no definitive evidence that the use of FFR improves early clinical outcomes after CABG, with the exception of a simplification of the procedure. FFR use may help in defining the indication to the use arterial grafts, but there is no evidence that preoperative FFR lead to any benefits in terms of patency when venous grafts are used.

On these grounds a large multicentric all-comers observational study is planned. The aim is to achieve a real-life picture of the FFR practice in CABG across several European and non-European units. This study will inform on the effective use rate of FFR in the CABG practice and its clinical effectiveness when compared to standard angiography-based CABG.

Detailed description: Background The use of fractional flow reserve (FFR) to guide coronary artery bypass graft (CABG) is controversial. A large retrospective study on 627 patients by Toth et al. showed that FFR-guided surgery was associated with a lower number of graft anastomoses and a lower rate of on-pump surgery compared with angiography-guided coronary artery bypass graft surgery. This did not result in a higher event rate during up to 36 months of follow-up and was associated with a lower rate of angina. The six years follow-up of the same study showed that FFR-guided CABG was associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG.

However, the three randomized studies on FFR-based CABG have achieved contradictive results. The FARGO (Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization) and GRAFFITI (GRAft patency after FFR-guided versus angiography-guided CABG) did not report a significant impact on hard outcomes at 1 year. Conversely, the IMPAG trial support the use of preoperative FFR in total arterial CABG. Authors found a significant association between the preoperative FFR measurement of the target vessel and the anastomotic functionality at 6 months, with a cut-off of 0.78. Authors concluded that integration of FFR measurement into the preoperative diagnostic workup could lead to improved anastomotic graft function.

The currently available randomized evidences might have been flawed by limitations including underpowering, entry selectivity bias, cross over among treatment, difference in the type of conduits used and presence of unexpected confounders related to surgeons' reluctance to base their surgical strategy on FFR. These drawbacks not only hamper the reliability of the results, but more importantly, reduce their translatability to the real-life clinical world.

Given the lack of definitive evidences and the difficulty of RCT to capture the real-life scenario of the clinical practice, we plan to perform a large multicentric all-comers study comparing the practice of FFR in CABG across several European and non-European units.

The main aim is to obtain information on

* Use rate of FFR in preoperative planning of surgical candidates
* Effective adherence to FFR guidance during elective surgery and identification of factors eventually limiting observance to FFR information
* Short and long-term outcomes of FFR-based CABG in comparison to standard angiography-based CABG
* Post hoc analysis in relation to type of conduit used, completeness of revascularization, surgeon experience, volume/outcome relationship.

Eligibility criteria: Inclusion Criteria:

* all-comers" including both elective and urgent (and urgent in-house) isolated CABG cases

Exclusion Criteria:

* patients undergoing emergency revascularization for iatrogenic complications or other conditions that would prevent a careful analysis of angiographic severity of the lesions

Primary outcomes:
measure: Use rate of FFR in preoperative planning of surgical candidates
timeFrame: 10 years
measure: Effective adherence to FFR guidance during elective surgery and identification of factors eventually limiting observance to FFR information
timeFrame: 10 years
measure: Survival of FFR-based CABG in comparison to standard angiography-based CABG
timeFrame: 10 years
measure: Myocardial infarction rate in FFR-based CABG in comparison to standard angiography-based CABG
timeFrame: 10 years
measure: Major cardiovascular events rate in FFR-based CABG in comparison to standard angiography-based CABG
timeFrame: 10 years
measure: Target vessel revascularization rate in FFR-based CABG in comparison to standard
timeFrame: 10 years
measure: Freedom from coronary intervention in FFR-based CABG compared to standard angiography-based CABG
timeFrame: 10 years
Secondary outcomes:
measure: Type of conduit used
timeFrame: 10 years
measure: Completeness of revascularization
timeFrame: 10 years
measure: Surgeon experience effect
timeFrame: 10 years
measure: Volume/outcome relationship
timeFrame: 10 years
Other outcomes:
Locations:
Study officials:
affiliation: University of Glasgow
name: Cristiano Spadaccio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sundermann S, Dademasch A, Praetorius J, Kempfert J, Dewey T, Falk V, Mohr FW, Walther T. Comprehensive assessment of frailty for elderly high-risk patients undergoing cardiac surgery. Eur J Cardiothorac Surg. 2011 Jan;39(1):33-7. doi: 10.1016/j.ejcts.2010.04.013.
citation: Coulson TG, Mullany DV, Reid CM, Bailey M, Pilcher D. Measuring the quality of perioperative care in cardiac surgery. Eur Heart J Qual Care Clin Outcomes. 2017 Jan 1;3(1):11-19. doi: 10.1093/ehjqcco/qcw027.
citation: Authors/Task Force members; Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. No abstract available.
citation: Toth G, De Bruyne B, Casselman F, De Vroey F, Pyxaras S, Di Serafino L, Van Praet F, Van Mieghem C, Stockman B, Wijns W, Degrieck I, Barbato E. Fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery. Circulation. 2013 Sep 24;128(13):1405-11. doi: 10.1161/CIRCULATIONAHA.113.002740. Epub 2013 Aug 28.
citation: Fournier S, Toth GG, De Bruyne B, Johnson NP, Ciccarelli G, Xaplanteris P, Milkas A, Strisciuglio T, Bartunek J, Vanderheyden M, Wyffels E, Casselman F, Van Praet F, Stockman B, Degrieck I, Barbato E. Six-Year Follow-Up of Fractional Flow Reserve-Guided Versus Angiography-Guided Coronary Artery Bypass Graft Surgery. Circ Cardiovasc Interv. 2018 Jun;11(6):e006368. doi: 10.1161/CIRCINTERVENTIONS.117.006368.
citation: Thuesen AL, Riber LP, Veien KT, Christiansen EH, Jensen SE, Modrau I, Andreasen JJ, Junker A, Mortensen PE, Jensen LO. Fractional Flow Reserve Versus Angiographically-Guided Coronary Artery Bypass Grafting. J Am Coll Cardiol. 2018 Dec 4;72(22):2732-2743. doi: 10.1016/j.jacc.2018.09.043.
citation: Toth GG, De Bruyne B, Kala P, Ribichini FL, Casselman F, Ramos R, Piroth Z, Fournier S, Piccoli A, Van Mieghem C, Penicka M, Mates M, Nemec P, Van Praet F, Stockman B, Degriek I, Barbato E. Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting: the GRAFFITI trial. EuroIntervention. 2019 Dec 6;15(11):e999-e1005. doi: 10.4244/EIJ-D-19-00463.
citation: Glineur D, Grau JB, Etienne PY, Benedetto U, Fortier JH, Papadatos S, Laruelle C, Pieters D, El Khoury E, Blouard P, Timmermans P, Ruel M, Chong AY, So D, Chan V, Rubens F, Gaudino MF. Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial. Eur Heart J. 2019 Aug 1;40(29):2421-2428. doi: 10.1093/eurheartj/ehz329.
citation: Spadaccio C, Glineur D, Barbato E, Di Franco A, Oldroyd KG, Biondi-Zoccai G, Crea F, Fremes SE, Angiolillo DJ, Gaudino M. Fractional Flow Reserve-Based Coronary Artery Bypass Surgery: Current Evidence and Future Directions. JACC Cardiovasc Interv. 2020 May 11;13(9):1086-1096. doi: 10.1016/j.jcin.2019.12.017. Epub 2020 Mar 25.