fame 3 trial · 2015. 1. 29. · functional syntax score without ffr reclassifies > 30% of cases...
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FAME 3 Trial: FFR-Guided PCI vs. CABG
William F. Fearon, M.D.
Associate Professor of Medicine
Director, Interventional Cardiology
Stanford University Medical Center
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Background:
SYNTAX Trial One Year MACCE Results
Serruys, et al. NEJM 2009;360:961-72.
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Background:
At one year in the SYNTAX trial:
Cardiac death was higher in PCI arm vs. CABG
(3.7 vs. 2.1%, p=0.05)
MI was higher in PCI arm vs. CABG
(4.8 vs. 3.3%, p=0.11)
Stroke was higher in CABG arm vs. PCI (2.2 vs.
0.6%, p=0.003)
Repeat revascularization was higher with PCI
(13.5 vs. 5.9%, p<0.001)
Serruys, et al. NEJM 2009;360:961-72.
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Background:
SYNTAX Trial Three Year MACCE Results
Kappetein, et al. Eur Heart J 2011;32:2125-34.
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Background:
At three years in the SYNTAX trial:
Cardiac death was higher in PCI arm vs. CABG
(6.0 vs. 3.6%, p=0.02)
MI was higher in PCI arm vs. CABG
(7.1 vs. 2.6%, p=0.002)
Stroke was higher in CABG arm vs. PCI (3.4 vs.
2.0%, p=0.07)
Repeat revascularization was higher with PCI (21
vs. 11%, p<0.001)
Kappetein, et al. Eur Heart J 2011;32:2125-34.
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Background:
Why should we expect a different result with
FAME 3?
2nd Generation DES outperform 1st Generation.
Fractional Flow Reserve-guided PCI outperforms
angiography-guided PCI.
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Background:
Dangas, et al. JACC Intv 2013;6:914-22.
3 Year Benefit of 2nd Generation DES in SPIRIT meta-analysis
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Background:
Dangas, et al. JACC Intv 2013;6:914-22.
3 Year Benefit of 2nd Generation DES in SPIRIT meta-analysis
Ischemia-driven TLR reduced from 8.2 to 6.0%, p=0.004
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Background: Randomized comparison of two 2nd generation DES
(Resolute and Xience stents)
Serruys, et al. NEJM 2010;363:136-46.
Target Lesion Failure
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Background: Randomized comparison of 2nd generation Resolute and Xience
stents in the TWENTE trial
Von Birgelen, et al. JACC 2012;59:1350-61.
Target Lesion Failure
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Background:
Why should we expect a different result with
FAME 3?
2nd Generation DES outperform 1st Generation.
Fractional Flow Reserve-guided PCI outperforms
angiography-guided PCI.
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Tonino, et al. New Engl J Med 2009;360:213-24.
3
8.79.5
11.1
18.3
1.8
5.76.5
7.3
13.2
0
5
10
15
20
Death MI Repeat
Revasc
Death/MI MACE
Angio-Guided FFR-Guided
p=0.02 p=0.04
%
~40%
~35% ~30%
~35%
~30%
FAME Study: One Year Outcomes 1,005 patients with MVD randomized to FFR or Angio-guided PCI
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20
0
10
%
SYNTAX
19.1
11.2
Implications of FAME
18.4
13.2
FAME
1 y
ea
r M
AC
E R
ate
s
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Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
Functional SYNTAX Score
Without FFR
Reclassifies > 30% of Cases
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Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
Functional SYNTAX Score
Without FFR With FFR
Reclassifies > 30% of Cases
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P < 0.01
Functional SYNTAX Score (FSS)
Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
32%
20%
34% 59%
FSS converts patients from higher to lower risk
and better discriminates risk for death/MI
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55 year old man with dyslipidemia, tobacco use and chest pain
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What should we do now?
Med Rx alone
PCI
Which vessels?
CABG
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FFR L Cx = 0.90
Resting Hyperemia
(IV adenosine)
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FFR RCA = 0.82
Resting Hyperemia
(IV adenosine)
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Summary of Case
Anatomic 3V CAD, functional 1V CAD
Successfully treated with single stent
<150 cc contrast, < 1 hour procedure
Angina free at 1 month
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FAME 3:
Fractional flow reserve (FFR)-guided
percutaneous coronary intervention (PCI)
using the 2nd generation Resolute DES in
patients with multivessel coronary artery
disease (CAD) will result in similar outcomes
to coronary artery bypass graft surgery
(CABG).
Hypothesis
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FAME 3:
The primary objective of the FAME 3 Trial is
to demonstrate that FFR-guided PCI with the
2nd generation Resolute DES is non-inferior
to CABG in patients with multivessel CAD.
Objective
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FAME 3:
Multicenter, worldwide, prospective,
randomized trial
Non-inferiority design
1500 patients from 50 sites
Plan for 2 years enrolment and up to 5 year
follow-up
Design
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All Comers with 3 V CAD
(not involving LM)
Heart team identifies lesions for PCI/CABG
and then patient is randomized
FFR-Guided PCI with Resolute DES
Stent all lesions with FFR ≤ 0.80
(n=750)
Perform CABG based on
coronary angiogram
(n=750)
Primary: One Year follow-up for Death, MI, CVA, Revascularization
Key Secondary: Three Year follow-up for Death/MI/CVA
Study Flow:
Non-inferior Design
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FAME 3:
Age ≥ 21 years
Three vessel CAD, defined as ≥ 50% diameter stenosis
by visual estimation in each of the three major epicardial
vessels, but not involving left main coronary artery, and
amenable to revascularization by both PCI and CABG as
determined by the Heart Team
Willing and able to provide informed, written consent
Inclusion Criteria
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FAME 3:
Requirement for other cardiac or non-cardiac surgical
procedure (e.g., valve replacement)
Previous CABG
Left main disease requiring revascularization
Cardiogenic shock and/or need for
mechanical/pharmacologic hemodynamic support
Recent STEMI (<5 days)
Ongoing Non STEMI with biomarkers (e.g., cardiac
troponin) still rising
Known left ventricular ejection fraction <30%
Key Exclusion Criteria
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FAME 3:
Primary Endpoint:
One year rate of Death, MI, Stroke and
Revascularization
Key Secondary Endpoint:
Three year rate of Death, MI and Stroke
Major Endpoints
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FAME 3:
MACCE rate at 1 and 6 months, 3 years and 5 years
Stent thrombosis (ARC definition) and graft occlusion at
each time point
Bleeding complication
Significant arrhythmia
Development of acute renal failure
Length of hospitalization
Rehospitalization
Quality of life and cost-effectiveness
Utility of Functional SYNTAX Score
Secondary Endpoints
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FAME 3
Investigator initiated trial
Coordinated by Stanford with support of a
CRO
Funded by research grants from Medtronic
and St. Jude Medical
Independent DSMB and CEC
Study Organization
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Conclusion:
By incorporating FFR-guided PCI and
utilizing the 2nd generation Resolute Integrity
stent, FAME 3 aims to demonstrate that FFR-
guided PCI is non-inferior to CABG in
patients with 3-vessel coronary disease not
involving the left main coronary artery.