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,

• n behalf of the FUTURE trial investigators, France

NCT01881555

Background

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

• In registries, FFR modifies PCI revascularization strategy in nearly 4 /10 patients 3

3 Van Belle et al. Circulation 2014;129:173

• 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

2 Tonino et al. JACC 2010;55:2816

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 Study Hypothesis

• Superiority design for 30% lower RRR MACE at 1 year in the FFR group
• 1728 patients to be recruited (864/group)
• 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)

FUTURE Primary Composite Endpoint, at one year All cause mortality + Myocardial Infarction + Repeat revascularization + Stroke

All-comer Patient with stable or stabilized angina Multivx-disease (>50% stenosis) including LAD at the time of angiography Randomisation 1:1 Only lesions with FFR≤0.80 included in stratification All lesions with %S>50 included in stratification FFR on all target lesions PCI + OMT CABG + OMT OMT only non-invasive tests allowed FFR-guided Angio-guided

Study design

PCI + OMT CABG + OMT OMT only

exclusion criteria STEMI<12h no LAD disease CI to FFR FFR>0.80 lesions disregarded for TT

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

Population - ITT

Variable Control group FFR group P-value 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

n=937

Angio and Functionnal characteristics

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

79% 12% 9% 71% 12% 17%

ad hoc PCI 91% ad hoc PCI 90%

Treatment decision

Medication at discharge Control group (n=467) FFR group (n=460) P-value† 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 Statin (no) (%) 418 (90) 425 (92) 0.13 ACE inhibitor-ARBs (no) (%) 355 (76) 350 (76) 0.98 Insulin (no) (%) 39 (8) 59 (13) 0.03

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

Primary endpoint (death – MI – revasc – stroke) median FU at 2 years - ITT

Hazard ratio 0.99 (05% CI, 0.75-1.30) P=0.93 Primary Composite Endpoint

Endpoints at one year - ITT

Events Control group (n=467) FFR group (n=460) Hazard Ratio (95%CI) P value Composite endpoint (no.) (%) 67 (14.4) 67 (14.6) 0.97 (0.69-1.36) 0.85 Death from any cause (no.) (%) 7 (1.5) 17 (3.7) 2.34 (0.97–5.68) 0.036 (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

Stable angina Atypical chest pain ACS OMT PCI CABG Syntax Score ≤22 22< Syntax Score ≤32 Syntax Score >32 Diabetes No Diabetes

• verall

Favors FFR Favors control

Control group FFR group P-value Characteristics of deaths n Cardiovascular death (n,%) Diabetes (%) ACS (%) LVEF SYNTAX score Three-vx disease (%) 7 5/7 (71) 4/7 (57) 3/7 (43) 43±16 16±7 1/7 (14) 17 12/17 (71) 10/17 (59) 7/17 (41) 42±13 24±10 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

All-cause mortality: exploratory analysis only in death cases

Conclusions

Ø The FUTURE trial was prematurely halted because of an excess of all-cause mortality in the FFR group. 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 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

Ø FFR based strategy decreases the rate of revascularization largely dominated by PCI Place of FFR for treatment strategy decision in multivx-disease?

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

Population characteristics among treatment arms

Control group (n=467) FFR group (n=460) P-value PCI SYNTAX score (mean ± SD) 17.3±7.2 18.8±7.7 0.007

• No. of stents/patient

2.2±1.2 2.1±1.2 0.54 Drug-Eluting Stents (no) (%) 745 (94) 657 (95) 0.58 Ad hoc PCI (no.) (%) 334/366 (91) 296/328 (90) 0.74 CABG SYNTAX score (mean ± SD) 25.5±9.0 23.5±6.0 0.44 SYNTAX score>32 (no.) (%) Mean of total anastomoses 13 (23) 2.9±0.9 4 (7) 2.9±0.9 0.04 0.81 Mean of arterial anastomoses 2.3±0.9 2.2±0.9 0.40 Control group (n=467) FFR group (n=460) P-value Medication at discharge (Optimal Medical Treatment only) 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 Statin (no) (%) 418 (90) 425 (92) 0.13 ACE inhibitor-ARBs (no) (%) 355 (76) 350 (76) 0.98 Insulin (no) (%) 39 (8) 59 (13) 0.03 Oral Antidiabetic (no) (%) 109 (23) 87 (19) 0.1