TCT, October 14 th, 2008 Nico H.J.Pijls, MD, PhD Catharina Hospital, Eindhoven The Netherlands, The...

TCT, October 14 th , 2008TCT, October 14 th , 2008

Nico H.J.Pijls, MD, PhDNico H.J.Pijls, MD, PhDCatharina Hospital, EindhovenCatharina Hospital, Eindhoven The Netherlands,The Netherlands,on behalf of the on behalf of the FAME investigatorsFAME investigators

FRACTIONAL FLOW RESERVE FRACTIONAL FLOW RESERVE versusversus ANGIOGRAPHY ANGIOGRAPHY FOR GUIDING PCI IN PATIENTS WITH FOR GUIDING PCI IN PATIENTS WITH MULTIVESSEL CORONARY ARTERY DISEASEMULTIVESSEL CORONARY ARTERY DISEASE

Late Breaking Trial atLate Breaking Trial at

FAME study: disclosureFAME study: disclosure

To perform the FAME study, an unrestrictedTo perform the FAME study, an unrestrictedinstitutional research grant was obtained from RADI institutional research grant was obtained from RADI Medical SystemsMedical Systems

I have no further conflict of interest to declareI have no further conflict of interest to declare

FFractional Flow Reserve ractional Flow Reserve

versusversus

AAngiography forngiography for

MMultivessel ultivessel

EEvaluationvaluation

FRACTIONAL FLOW RESERVE FRACTIONAL FLOW RESERVE versusversus ANGIOGRAPHY ANGIOGRAPHY FOR GUIDING PCI IN PATIENTS WITH FOR GUIDING PCI IN PATIENTS WITH MULTIVESSEL CORONARY ARTERY DISEASEMULTIVESSEL CORONARY ARTERY DISEASE

FAME study: FAME study: BACKGROUND (1)BACKGROUND (1)

• Stenting of non-ischemic stenoses has no benefitStenting of non-ischemic stenoses has no benefit compared to medical treatment onlycompared to medical treatment only

• Stenting of ischemia-related stenoses improvesStenting of ischemia-related stenoses improves symptoms and outcomesymptoms and outcome

• In multivessel coronary disease (MVD), identifyingIn multivessel coronary disease (MVD), identifying which stenoses cause ischemia is difficult:which stenoses cause ischemia is difficult: Non-invasive tests are often unreliable in MVD andNon-invasive tests are often unreliable in MVD and coronary angiography often results in both under- coronary angiography often results in both under- or overestimation of functional stenosis severityor overestimation of functional stenosis severity

FAME study: FAME study: BACKGROUND (2)BACKGROUND (2)

• Fractional Flow Reserve (FFR),Fractional Flow Reserve (FFR), is the most accurate is the most accurate and selective index to indicate whether a particular and selective index to indicate whether a particular stenosis is responsible for inducible ischemiastenosis is responsible for inducible ischemia

• FFR can be easily determined in the cathlabFFR can be easily determined in the cathlab just prior to stentingjust prior to stenting

Therefore:Therefore:

• FFR guidance of PCI in patients withFFR guidance of PCI in patients with multivessel disease may improve outcomemultivessel disease may improve outcome

FAME study: FAME study: HYPOTHESISHYPOTHESIS

FFR – guided Percutaneous Coronary FFR – guided Percutaneous Coronary Intervention (PCI) in multivessel disease, Intervention (PCI) in multivessel disease, is superior to current is superior to current angiography – guided PCIangiography – guided PCI

FAME study: FAME study: DESIGNDESIGN

Randomized multicenter study in 1000 patients Randomized multicenter study in 1000 patients undergoing DES-stenting for multivessel disease undergoing DES-stenting for multivessel disease in 20 US and European centersin 20 US and European centers

Multivessel disease:Multivessel disease:Stenoses of > 50% in at least 2 of the 3 Stenoses of > 50% in at least 2 of the 3 majormajorcoronary arteriescoronary arteries

• independent core-labindependent core-lab• independent data analysisindependent data analysis• blinded adverse event committeeblinded adverse event committee

Participating CentersUSA (6)USA (6)

Stanford UniversityStanford University(William F. Fearon)(William F. Fearon)

Northeast Cardiology, Bangor, Northeast Cardiology, Bangor, Maine Maine (Peter N. Ver Lee)(Peter N. Ver Lee)University of LouisvilleUniversity of Louisville(Massoud Leesar)(Massoud Leesar)

St Louis UniversitySt Louis University(Michael Lim)(Michael Lim)

University Hospital VirginiaUniversity Hospital Virginia(Michael Ragosta)(Michael Ragosta)

University of South CarolinaUniversity of South Carolina(Eric Powers)(Eric Powers)

EUROPE (14)EUROPE (14)

King´s College Hospital, London) King´s College Hospital, London) (Ph.MacCarthy)(Ph.MacCarthy)

Cardiovascular Center Aalst Cardiovascular Center Aalst (B. De (B. De Bruyne)Bruyne)

Catharina Hospital Eindhoven Catharina Hospital Eindhoven (N.Pijls)(N.Pijls)

Rigshospitalet, Copenhagen Rigshospitalet, Copenhagen

((T.EngstromT.Engstrom))

Klinikum der Universitat Klinikum der Universitat MunchenMunchen(V.Klauss)(V.Klauss)

Aarhus University Hospital Aarhus University Hospital (Ole (Ole Frobert)Frobert)

University Hospital Bergmannsheil University Hospital Bergmannsheil

(Waldemar Bojara)(Waldemar Bojara)

Sodersjukhhuset, Stockholm Sodersjukhhuset, Stockholm (I (I Herzfeld)Herzfeld)

Helsingborgs Lasarett Helsingborgs Lasarett (F Schersten)(F Schersten)

Klinikum Darmstadt Klinikum Darmstadt (Gerald Werner)(Gerald Werner)

Bristol Royal Infirmary Bristol Royal Infirmary (A.Baumbach)(A.Baumbach)

Staedt. Krankenhaus, Bogenhausen Staedt. Krankenhaus, Bogenhausen (G.Riess)(G.Riess)

Glasgow Western Infirmary Glasgow Western Infirmary (Keith (Keith Oldroyd)Oldroyd)

Royal Victoria Hospital, Belfast Royal Victoria Hospital, Belfast (Ganesh Manoharan)(Ganesh Manoharan)

FAME studyFAME study

Steering Committee:Steering Committee:Nico H.J. Pijls, Eindhoven, Netherlands (PI)Nico H.J. Pijls, Eindhoven, Netherlands (PI)William F. Fearon, Stanford, CA, USA (PI)William F. Fearon, Stanford, CA, USA (PI)Bernard De Bruyne, Aalst, BelgiumBernard De Bruyne, Aalst, BelgiumPim A.L. Tonino, Eindhoven, NetherlandsPim A.L. Tonino, Eindhoven, Netherlands

Data analysis:Data analysis:Uwe Siebert, Boston, MA, USA and Hall, AUwe Siebert, Boston, MA, USA and Hall, ARafaele Gothe and Bernard Bornschein, Hall, AustriaRafaele Gothe and Bernard Bornschein, Hall, Austria

Clinical Events Committee:Clinical Events Committee:Eric Eeckhout, Lausanne, SwitzerlandEric Eeckhout, Lausanne, SwitzerlandMorton Kern, Irvine, CA, USAMorton Kern, Irvine, CA, USAMamdouh El Gamal, Eindhoven, NLMamdouh El Gamal, Eindhoven, NLJohn Hodgson, Phoenix, AZ, USAJohn Hodgson, Phoenix, AZ, USAEmanuele Barbato, Naples, ItalyEmanuele Barbato, Naples, Italy

FAME study: FAME study: Study PopulationStudy Population

The FAME study was designed to The FAME study was designed to reflect daily practicereflect daily practicein performing PCI in patients in performing PCI in patients with multivessel diseasewith multivessel disease

Inclusion criteria:Inclusion criteria:• ALLALL patients with multivessel disease patients with multivessel disease• At least 2 stenoses ≥ 50% in 2 or 3 major epicardialAt least 2 stenoses ≥ 50% in 2 or 3 major epicardial coronary artery disease, amenable for stentingcoronary artery disease, amenable for stenting

Exclusion criteria:Exclusion criteria:• Left main disease or previous bypass surgeryLeft main disease or previous bypass surgery• ST-elevation MI with CK > 1000 U/l within last 5 daysST-elevation MI with CK > 1000 U/l within last 5 days• extremely tortuous or calcified coronary arteriesextremely tortuous or calcified coronary arteries

Note:Note: patients with previous PCI were not excluded patients with previous PCI were not excluded

Angiography-guided PCI FFR-guided PCI

Measure FFR in all indicated stenoses

Stent all indicated stenoses

Stent only those stenoses with FFR ≤ 0.80

Randomization

Indicate all stenoses ≥ 50% considered for stenting

Patient with stenoses ≥ 50% in at least 2 of the 3 major

epicardial vessels

1-year follow-up

FLOW CHART

FAME study: FAME study: PRIMARY ENDPOINTPRIMARY ENDPOINT

Composite of death, myocardial infarction, Composite of death, myocardial infarction, or repeat revascularization (“MACE”) or repeat revascularization (“MACE”) at 1 year at 1 year

FAME study: FAME study: SECONDARY ENDPOINTSSECONDARY ENDPOINTS

• individual components of MACE at 1 yearindividual components of MACE at 1 year• functional classfunctional class• use of anti-anginal drugsuse of anti-anginal drugs• health-related quality of life (EuroQOL-5D)health-related quality of life (EuroQOL-5D)

• procedure timeprocedure time• amount of contrast agent used during procedureamount of contrast agent used during procedure• cost of the procedurecost of the procedure

Assessed for eligibilityN=1905

Angiography-guided PCI

N=496

FFR-guided PCIN=509

Lost to follow-upN=8

AnalyzedN=496

AnalyzedN=509

RandomizedN=1005

Lost to follow-upN=11

Not eligible N= 900

Left main stenosis N= 157

Extreme coronary tortuosity

or calcification N= 217

No informed consent N= 105

Contra-indication for DES N= 86

Participation in other study N= 94

Logistic reasons N= 210

Other reasons N= 31

CONSORT-E CHART

• PCI according to local routinePCI according to local routine• Only drug-eluting stents (DES)Only drug-eluting stents (DES)• FFR measured by Pressure WireFFR measured by Pressure Wire

((Certus wire, RADI Medical SystemsCertus wire, RADI Medical Systems))• hyperemia induced by i.v. adenosine 140 µg/kg/min hyperemia induced by i.v. adenosine 140 µg/kg/min

in femoral veinin femoral vein• EKG, CK, CK-MB, etc during hospital stayEKG, CK, CK-MB, etc during hospital stay• Follow-up at 1 month, 6 months, 1 yearFollow-up at 1 month, 6 months, 1 year• Also in case of repeat-procedure , strictly adherence Also in case of repeat-procedure , strictly adherence

to initial randomizationto initial randomization

FAME study: FAME study: TreatmentTreatment

ANGIO-group

N=496

FFR-group

N=509

P-P-valuevalue

Age, Age, meanmean±SD±SD 64±10 65±10 0.470.47

Male, Male, %% 73 75 0.300.30

Diabetes, Diabetes, %% 25 24 0.650.65

Hypertension, Hypertension, %% 66 61 0.100.10

Current smoker, Current smoker, %% 32 27 0.120.12

Hyperlipidemia, Hyperlipidemia, %% 74 72 0.620.62

Previous MI, Previous MI, %% 36 37 0.840.84

Unstable angina, Unstable angina, %% 36 29 0.110.11

Previous PCI , Previous PCI , %% 26 29 0.340.34

LVEF, LVEF, meanmean±SD±SD 57±12 57±11 0.920.92

LVEF < 50% , LVEF < 50% , %% 27 29 0.470.47

FAME study: FAME study: Baseline Characteristics (1)Baseline Characteristics (1)


ANGIO-group

N=496

FFR-group

N=509P-valueP-value

# indicated lesions per patient# indicated lesions per patient 2.7±0.9 2.8±1.0 0.340.34


ANGIO-group

N=496

FFR-group

N=509P-valueP-value


Reference diameter Reference diameter (mm)(mm) 2.5±0.6 2.5±0.7 0.810.81

% stenosis severity% stenosis severity 61±17 60±18 0.240.24

MLD (mm)MLD (mm) 1.0±0.4 1.0±0.5 0.350.35


ANGIO-group

N=496

FFR-group

N=509P-valueP-value


Reference diameter Reference diameter (mm)(mm) 2.5±0.6 2.5±0.7 0.810.81

% stenosis severity% stenosis severity 61±17 60±18 0.240.24

MLD (mm)MLD (mm) 1.0±0.4 1.0±0.5 0.350.35

50-70% narrowing, 50-70% narrowing, No (%)No (%) 550 (41) 624 (44) --

70-90% narrowing,70-90% narrowing, No (%) No (%) 553 (41) 530 (37) --

90-99% narrowing,90-99% narrowing, No (%) No (%) 207 (15) 202(14) --

Total occlusion, Total occlusion, No (%)No (%) 40 (3) 58 (4) --

Patients with ≥1 total occlusion Patients with ≥1 total occlusion (%)(%) 7.5 10.6 0.080.08

ANGIO-group

N=496

FFR-group

N=509P-valueP-value

# indicated lesions per patient# indicated lesions per patient 2.7 ± 0.9 2.8 ± 1.0 0.340.34

FFR resultsFFR resultsLesions succesfully measured, Lesions succesfully measured, No No (%)(%)

- 1329 (98%) --

Lesions with FFR ≤ 0.80 ,Lesions with FFR ≤ 0.80 ,No (%)No (%) - 874 (63%) --

Lesions with FFR > 0.80 ,Lesions with FFR > 0.80 ,No (%)No (%) - 513 (37%) --

FFR in ischemic lesionsFFR in ischemic lesions - 0.60 ± 0.14 --

FFR in non-ischemic lesionsFFR in non-ischemic lesions - 0.88 ± 0.05 --

FAME study: FAME study: Procedural Results (1)Procedural Results (1)

ANGIO-group

N=496

FFR-group

N=509P-valueP-value

# indicated lesions per patient# indicated lesions per patient 2.7 ± 0.9 2.8 ± 1.0 0.340.34

FFR resultsFFR resultsLesions succesfully measured, Lesions succesfully measured, No No (%)(%)

- 1329 (98%) --

Lesions with FFR ≤ 0.80 ,Lesions with FFR ≤ 0.80 ,No (%)No (%) - 874 (63%) --

Lesions with FFR > 0.80 ,Lesions with FFR > 0.80 ,No (%)No (%) - 513 (37%) --

stents per patientstents per patient 2.7 ± 1.2 1.9 ± 1.3 <0.001<0.001

Lesions succesfully stented Lesions succesfully stented (%)(%) 92% 94% --

DES, total, DES, total, NoNo 1359 980 --



ANGIO-group

N=496

FFR-group

N=509P-valueP-value

Procedure time (min)Procedure time (min) 70 ± 44 71 ± 43 0.510.51


ANGIO-group

N=496

FFR-group

N=509P-valueP-value


Contrast agent used (ml)Contrast agent used (ml) 302 ± 127 272 ± 133 <0.001<0.001


ANGIO-group

N=496

FFR-group

N=509P-valueP-value



Materials used at procedure Materials used at procedure

(US $)(US $)

6007 5332 <0.001<0.001


ANGIO-group

N=496

FFR-group

N=509P-valueP-value



Materials used at procedure Materials used at procedure

(US $)(US $)

6007 5332 <0.001<0.001

Length of hospital stay (days)Length of hospital stay (days) 3.7 ± 3.5 3.4 ± 3.3 0.050.05

ANGIO-group

N=496

FFR-group

N=509P-valueP-value

Events at 1 year, No (%)Events at 1 year, No (%)

Death, MI, CABG, or repeat-PCIDeath, MI, CABG, or repeat-PCI 91 (18.4) 67 (13.2) 0.020.02

FAME study: FAME study: Adverse Events at 1 yearAdverse Events at 1 year

ANGIO-group

N=496

FFR-group

N=509P-valueP-value



DeathDeath 15 (3.0) 9 (1.8) 0.190.19

Death or myocardial infarctionDeath or myocardial infarction 55 (11.1) 37 (7.3) 0.040.04

CABG or repeat PCICABG or repeat PCI 47 (9.5) 33 (6.5) 0.080.08


ANGIO-group

N=496

FFR-group

N=509P-valueP-value



DeathDeath 15 (3.0) 9 (1.8) 0.190.19



Total no. of MACETotal no. of MACE 113 76 0.020.02


ANGIO-group

N=496

FFR-group

N=509P-valueP-value



DeathDeath 15 (3.0) 9 (1.8) 0.190.19



Total no. of MACETotal no. of MACE 113 76 0.020.02

Myocardial infarction, specifiedMyocardial infarction, specified

All myocardial infarctionsAll myocardial infarctions 43 (8.7) 29 (5.7) 0.070.07

Small periprocedural CK-MB 3-5 x NSmall periprocedural CK-MB 3-5 x N 16 12

Other infarctions (“late or large”)Other infarctions (“late or large”) 27 17


FFR-guided

30 days2.9% 90 days

3.8% 180 days4.9% 360 days

5.3%

Angio-guided

absolute difference in MACE-free survival

FAME study: FAME study: Event-free Survival Event-free Survival

ANGIO-group

N=496

FFR-group

N=509P-valueP-value

Patients without event and free Patients without event and free

from anginafrom angina326 (68) 360 (73) 0.070.07

Patients free from angina, No. (%)Patients free from angina, No. (%) 374 (78) 399 (81) 0.200.20

Number of anti-anginal meds, No.Number of anti-anginal meds, No. 1.2 ± 0.7 1.2 ± 0.8 0.480.48

EQ-5D visual analogue scaleEQ-5D visual analogue scale 74 ± 16 75 ± 16 0.650.65

FAME study: FAME study: Functional Class at 1 Year Functional Class at 1 Year

FAME study: FAME study: CONCLUSIONS (1)CONCLUSIONS (1)

Routine measurement of FFR during PCI with DES Routine measurement of FFR during PCI with DES in patients with multivessel disease, when in patients with multivessel disease, when compared to current angiography guided strategycompared to current angiography guided strategy

• reduces the rate of the composite endpoint of reduces the rate of the composite endpoint of

death, myocardial infarction, re-PCI and CABG death, myocardial infarction, re-PCI and CABG

at 1 year by at 1 year by ~ ~ 30%30%

• reduces mortality and myocardial infarction at reduces mortality and myocardial infarction at

1 year by 1 year by ~ ~ 35 %35 %


Routine measurement of FFR during PCI with DES Routine measurement of FFR during PCI with DES in patients with multivessel disease, when in patients with multivessel disease, when compared to current angiography guided strategy,compared to current angiography guided strategy,furthermore:furthermore:

• is cost-saving and does not prolong the procedureis cost-saving and does not prolong the procedure

• reduces the number of stents usedreduces the number of stents used

• decreases the amount of contrast agent useddecreases the amount of contrast agent used

• results in a similar, if not better, functional statusresults in a similar, if not better, functional status

Routine measurement of FFR during DES-stenting Routine measurement of FFR during DES-stenting in patients with multivessel disease is superior in patients with multivessel disease is superior to current angiography guided treatment.to current angiography guided treatment.

It improves outcome of PCI significantlyIt improves outcome of PCI significantly

It supports the evolving paradigm of It supports the evolving paradigm of

“ “Functionally Complete Revascularization”,Functionally Complete Revascularization”, i.e. stenting of ischemic lesions and i.e. stenting of ischemic lesions and medical treatment of non-ischemic ones.medical treatment of non-ischemic ones.


TCT, October 14 th, 2008 Nico H.J.Pijls, MD, PhD Catharina Hospital, Eindhoven The Netherlands, The...

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