FUnctional Testing Underlying REvascularization The FUTURE trial - PowerPoint PPT Presentation

FUnctional Testing Underlying REvascularization The FUTURE trial Gilles Rioufol, François Roubille, Thibault Perret, Pascal Motreff, Denis Angoulvant, Yves Cottin, Ludovic Meunier,Nathan Mewton, Michel Ovize, Gérard Finet, on behalf of the FUTURE trial investigators, France NCT01881555

Background - Fractional Flow Reserve (FFR) is recommended for guiding PCI in multivessel disease patients eligible for PCI (IIaB) 1 . - In randomized trial, less than half of patients with angiographically multivessel disease eligible for PCI has actually functional multivessel disease (FFR≤0.80) 2 - In registries, FFR modifies PCI revascularization strategy in nearly 4 /10 patients 3 Whether FFR helps to decide among different treatment strategies (PCI or CABG or optimal medical treatment only (OMT)) remains unknown 1 Windecker et al. EHJ 2014;35:2541 2 Tonino et al. JACC 2010;55:2816 3 Van Belle et al. Circulation 2014;129:173

FUTURE Study Hypothesis In multivessel disease patients, does FFR help to guide treatment strategy (PCI or CABG or medical treatment only) and thereby improve clinical prognosis compared to traditional management ? FUTURE Primary Composite Endpoint, at one year All cause mortality + Myocardial Infarction + Repeat revascularization + Stroke - Multicenter, randomized, prospective, open-label, controlled study in 31 french centers - Academic Sponsor : Hospices Civils de Lyon - NCT01881555 - French Health Ministry grant (Programme Hospitalier de Recherche Clinique 2011) - Superiority design for 30% lower RRR MACE at 1 year in the FFR group - 1728 patients to be recruited (864/group)

Study design All-comer Patient with stable or stabilized angina Multivx-disease (>50% stenosis) including LAD at the time of angiography exclusion criteria Randomisation 1:1 STEMI<12h no LAD disease CI to FFR FFR-guided Angio-guided non-invasive tests FFR>0.80 lesions FFR on all target lesions disregarded for TT allowed Only lesions with FFR≤0.80 All lesions with %S>50 included in stratification included in stratification CABG PCI OMT only CABG PCI OMT only + OMT + OMT + OMT + OMT

Recruitement stop at n=938 patients after DSMB recommendation All-cause death at one year - safety analysis

Population - ITT Variable Control group FFR group P-value n=937 Patient characteristics (n=467) (n=460) Age (yr) 66±11 65±10 0.16 Male (no.) (%) 385 (82) 393 (85) 0.22 Diabetes (no.) (%) 147 (32) 143(31) 0.90 Renal insufficiency (no..) (%) 180 (39) 188 (41) 0.47 History of MI (no.) (%) 100 (21) 90 (20) 0.51 History of PCI (no.) (%) 127 (27) 115 (25) 0.45 History of stroke (no.) (%) 27(6) 13 (3) 0.03 Clinical presentation ACS (no.) (%) 213 (46) 216 (47) 0.64 Including STEMI (no.) (%) 89 (19) 92 (20) 0.72 Stable angina (no.) (%) 102 (22) 89 (19) 0.35 LVEF (total no.) 56±11 (341) 55±12 (331) 0.48

Angio and Functionnal characteristics Variable Control group FFR group P-value Angiography findings FFR findings FFR group Radial access (no.) (%) 428 (92) 412 (90) 0.28 Patients with FFR (no) (%) 450 (98) 2 significant lesions (no.) (%) 223 (48) 201 (44) 0.77 FFR complication (no.) (%) 9/450 (2) 3 significant lesions (no) (%) 231 (50) 247 (54) 0.33 Lesions with FFR – no. /pt 1.38±1 LM coronary lesion (no) (%) 50 (11) 58 (13) 0.37 Mean FFR 0.77±0.13 SYNTAX score (total no.) 18±8 (451) 19±8 (452) 0.27 FFR>0.80 lesions (no.)(%) 470/1090 (43) Lesions characteristics Total no. of lesions 1634 1632 >50% stenosis/ pt (median) 3 (2-4) 3 (2-4) 0.50

Treatment decision 12% 12% Medication at discharge Control group FFR group P-value † (n=467) (n=460) Aspirin (no) (%) 439 (94) 445 (97) 0.048 Other antiplatelet (no) (%) 408 (87) 387(84) 0.16 Beta-blocker (no) (%) 383 (82) 387 (84) 0.39 79% 71% Statin (no) (%) 418 (90) 425 (92) 0.13 ACE inhibitor-ARBs (no) (%) 355 (76) 350 (76) 0.98 ad hoc PCI ad hoc PCI Insulin (no) (%) 39 (8) 59 (13) 0.03 91% 90% 17% 9%

Primary endpoint (death – MI – revasc – stroke) at one year - ITT

Primary endpoint (death – MI – revasc – stroke) median FU at 2 years - ITT Primary Composite Endpoint Hazard ratio 0.99 (05% CI, 0.75-1.30) P=0.93

Endpoints at one year - ITT Events Control group FFR group Hazard Ratio P value (n=467) (n=460) (95%CI) Composite endpoint (no.) (%) 67 (14.4) 67 (14.6) 0.97 (0.69-1.36) 0.85 0.036 Death from any cause (no.) (%) 7 (1.5) 17 (3.7) 2.34 (0.97–5.68) (by logrank test) Cardiovascular death (no.) (%) 5 (1.1) 12 (2.6) 2.37 (0.83-6.76) 0.11 Myocardial infarction (no.) (%) 28 (6) 28 (6.1) 1.03 (0.61-1.74) 0.90 Stroke (no.) (%) 7 (1.5) 1 (0.2) 0.13 (0.02-1.07) 0.06 Unplanned revascularization (no.) (%) 46 (9.9) 37 (8) 0.79 (051-1.22) 0.28

Primary-endpoint: Pre-specified sub-group analysis - ITT Favors FFR Favors control overall Diabetes No Diabetes Syntax Score ≤22 22< Syntax Score ≤32 Syntax Score >32 Stable angina Atypical chest pain ACS OMT PCI CABG

All-cause mortality: exploratory analysis only in death cases Control group FFR group P-value Characteristics of deaths n 7 17 Cardiovascular death (n,%) 5/7 (71) 12/17 (71) Diabetes (%) 4/7 (57) 10/17 (59) ACS (%) 3/7 (43) 7/17 (41) LVEF 43±16 42±13 SYNTAX score 16±7 24±10 Three-vx disease (%) 1/7 (14) 14/17 (82) All-cause death analysis SYNTAX score ≤32 (n, %) 7/433 (1.6) 13/436 (3.0) 0.18 SYNTAX score >32 (n, %) 0/29 (0) 4/23 (17.4) 0.02 OMT (n, %) 0/43 (0) 3/78 (3.9) 0.20 PCI (%) 7/369 (1.9) 13/328 (4.0) 0.10 CABG (%) O/55 (0) 1/54 (1.9) 0.31

Conclusions Place of FFR for treatment strategy decision in multivx-disease? Ø FFR based strategy decreases the rate of revascularization largely dominated by PCI Ø Treatment decision based on FFR in all-comer multivessel-disease patients did not demonstrate any improvement in the primary endpoint at one year. Ø The FUTURE trial was prematurely halted because of an excess of all-cause mortality in the FFR group. Ø Hypothesis to explain this excess of mortality: Lower than expected rate of CABG in multivessel disease patients • high rate of PCI in severe patients with Syntax Score >32, • high rate of ad hoc PCI •

Aknowledgments Primary Investigators (con’t) Steering committee: Guillaume Cayla, Nîmes Gilles Rioufol, Lyon Brahim Harbaoui, Lyon Gérard Finet, Lyon Olivier Roth, Mulhouse Michel Ovize, Lyon Eric Van Belle, Lille Nathan Mewton, Lyon Christophe Pouillot, la Réunion DSMB Loïc Belle, Annecy Jacques Beaune, Lyon Jean-François Morelle, Caen Didier Carrié, Toulouse François-Xavier Soto, Auxerre Michel Cucherat, Lyon Christophe Caussin, Paris Coordination Bernard Bertrand, Grenoble Centre d’Investigation Clinique, Lyon Thierry Lefevre, Massy Biostatistics Patrick Dupouy, Melun Muriel Rabilloud, Lyon Pierre-François Lesault, Le Havre Primary Investigators Franck Albert, Chartres Gilles Rioufol, Lyon Olivier Barthelemy, Paris Nathan Mewton, Lyon Riadh Rihani, Lomme François Roubille, Montpellier René Koning, Rouen Thibault Perret, Lyon Laurent Leborgne, Amiens Pascal Motreff, Clermont-Ferrand Pierre Barnay, Avignon Denis Angoulvant, Tours Philippe Chapon, Valence Yves Cottin, Dijon Sebastien Armero, Marseille Ludovic Meunier, La Rochelle Antoine Lafont, Paris Pierre Coste, Bordeaux Christophe Piot, Montpellier

Population characteristics among treatment arms Control group FFR group P-value Control group FFR group P-value (n=467) (n=460) (n=467) (n=460) Medication at discharge (Optimal Medical Treatment only) PCI Aspirin (no) (%) 439 (94) 445 (97) 0.048 SYNTAX score (mean ± SD) 17.3±7.2 18.8±7.7 0.007 Other antiplatelet (no) (%) 408 (87) 387(84) 0.16 No. of stents/patient 2.2±1.2 2.1±1.2 0.54 Beta-blocker (no) (%) 383 (82) 387 (84) 0.39 Drug-Eluting Stents (no) (%) 745 (94) 657 (95) 0.58 Statin (no) (%) 418 (90) 425 (92) 0.13 Ad hoc PCI (no.) (%) 334/366 (91) 296/328 (90) 0.74 ACE inhibitor-ARBs (no) (%) 355 (76) 350 (76) 0.98 CABG Insulin (no) (%) 39 (8) 59 (13) 0.03 SYNTAX score (mean ± SD) 25.5±9.0 23.5±6.0 0.44 Oral Antidiabetic (no) (%) 109 (23) 87 (19) 0.1 SYNTAX score>32 (no.) (%) 13 (23) 4 (7) 0.04 Mean of total anastomoses 2.9±0.9 2.9±0.9 0.81 Mean of arterial anastomoses 2.3±0.9 2.2±0.9 0.40