Multivessel PCI in an Era

of Freedom and FAME

Michael J. Cowley, MD, FSCAI

Nothing to Disclose
 Multivessel CAD

• 2/3 of pts with symptomatic CAD

• More Complex disease
• Lower Success Rates
• Higher Complication Rates
• Less Complete Revascularization
Multivessel CAD
Issues

• Efficacy
• Appropriateness
Best Strategies for Multivessel CAD
• Efficacy of Alternative Therapies
• PCI vs CABG vs Medical Rx
• Completeness of Revascularization
• Optimal Techniques
• FFR-guided
• Radial Access
• Long-term Rx
• Aggressive risk factor modification
Best Strategies for Multivessel CAD
Traditional Approach

• Medical Rx
• PCI
• CABG
Best Strategies for Multivessel CAD
New Paradigm

• Optimal Medical Rx
• PCI + Medical Rx
• CABG + Medical Rx
 Multivessel PCI
Patient Selection

• Likelihood of Success
• Risk of Complications
• Adequacy of Revascularization
• Likelihood of Stent Thrombosis
• Likelihood of Restenosis
 Multivessel PCI
Patient Selection

• Safety
• Efficacy
• Durability
• Comparability with CABG
• Completeness of revascularization
• Compliance with dual antiplatelet Rx
 Multivessel PCI
Risk Assessment

• Clinical = Patient characteristics

Clinical syndrome
Co-morbid conditions
(HTN,DM,CRF,CHF)
LV function
• Angiographic
Extent CAD
Lesion Type and morphology
 PCI vs Medical Therapy in Stable CAD
Randomized Controlled Trials

TRIAL Mortality and MI Angina Relief QOL Repeat Revasc

RITA 2 No difference PCI PCI PCI

ACME No difference PCI PCI PCI
ACME 2 No difference PCI PCI
MASS No difference PCI No difference
MASS II No difference PCI PCI No difference
AVERT No difference PCI PCI No difference
TIME No difference PCI PCI PCI
COURAGE No difference No difference PCI PCI

Kereiakes et al: JACC 2007;50:1598-1603

 RCT of PCI vs MT for SIHD
Study Limitations

• Many pts has mild or no Sx

• Many had mild or no ischemia
• Most had Incomplete Revascularization
• Outdated techniques (few stents, no DES)
PCI vs Medical Therapy in Stable CAD
What Determines Outcome?

• Presence of Ischemia
• Severity of Ischemia
• Relief of Ischemia
Survival Benefit of Revascularization according
to Ischemic Risk
n= 3,521; mean F/U = 1.9 yr

8%
Medical Rx
p <0.0001
Cardiac death (%)

Revascularization 6.7%

6%
4.8%

4% 3.7%
3.3%
2.9%
1.8% 2.0%
2%
1.0%
1331 56 718 109 545 243 252 267
0%
1- 5% 5-10% 11-20% >20%
% Total ischemic myocardium
Hachamovitch R et al: Circulation 2003;107:2900-7
PCI Reduces Mortality vs Med Rx in
SIHD with Ischemia

• RCT with either ischemia or abnl FFR

• 4 RCT:
• ACME, Courage AHJ, FAME 2 and SWISS II
• n= 1,769 pts; F/U: 7 mo to 10 yrs
• Principal analysis: PCI vs MT
• Primary EP: Mortality

Kirtane A, Stone GW: TCT 2013

PCI vs MT in SIHD pts with Ischemia
All-Cause Mortality (HR analysis)

Kirtane A, Stone GW: TCT 2013

PCI vs MT in SIHD Pts with Ischemia

• 44% i in mortality by HR analysis:

HR: 0.56; p=0.02
• Mortality i from 6.0% to 3.2% by
Count analysis, p=0.01

Kirtane A, Stone GW: TCT 2013

Best Strategies for Multivessel CAD

PCI vs CABG
 PCI vs CABG
Contemporary Trials

• SYNTAX
• FREEDOM
 SYNTAX Trial Design
De novo disease (n=1800)

Limited Exclusion Criteria

Previous interventions
Acute MI with CPK>2x
Concomitant cardiac surgery

Left Main Disease 3 Vessel Disease

(isolated, +1, 2 or 3 vessels) (revasc all 3 vessel territories)

N=705 N=1095
Primary endpoint = death/MI/stroke/repeat revasc at 1 year

Serruys PW et al. NEJM 2009;360:961-72

 SYNTAX: 3VD Disease
5-year Outcomes (N=1095)
CABG (n=549) TAXUS (n=546)

p=0.006 p<0.001 p=0.66 p<0.001 p<0.001

40

37.5
30
25.4
Patients (%)

24.2
20
14.6
12.6
10.6
9.2
10
3.3 3.4 3.0
0
All Death MI CVA Revasc MACCE

Cumulative KM Event Rate; log-rank P value ITT population

SYNTAX: 5 Year Results (3V + LM)
All-Cause Mortality
CABG (N=897) TAXUS (N=903)
SYNTAX: 5 Year Results (3V + LM)
Cardiac Mortality
CABG (N=897) TAXUS (N=903)
SYNTAX: 5 Year Results (3V + LM)
Myocardial Infarction
CABG (N=897) TAXUS (N=903)
SYNTAX: 5 Year Results (3V + LM)
CVA
CABG (N=897) TAXUS (N=903)
SYNTAX: 5 Year Results (3V + LM)
Death / MI / CVA
CABG (N=897) TAXUS (N=903)
SYNTAX: 5 Year Results (3V + LM)
Repeat Revascularization
CABG (N=897) TAXUS (N=903)
SYNTAX: 5 Year Results (3V + LM)
MACCE
CABG (N=897) TAXUS (N=903)
MACCE at 5 yrs by SYNTAX Score Tercile
Low Scores (0-22)
MACCE at 5 yrs by SYNTAX Score Tercile
Intermediate Scores (23-32)
MACCE at 5 yrs by SYNTAX Score Tercile
High Scores (33)
 FREEDOM: 1900 pts with diabetes + MVD
randomized to SES/PES vs CABG
1 Endpoint: Death, Stroke, or MI
30
PCI/DES
26.6%
Death, Stroke, MI, %

CABG
20

13.0% 18.7%

10
11.9%
p = 0.005
0
0 1 2 3 4 5 6
Years
PCI/DES 953 848 788 625 416 219 40
CABG 943 814 758 613 422 221 44

Farkouh ME et al: NEJM 2012

 Death, Stroke, MI by Syntax Score
SYNTAX Score  22 (n=669) SYNTAX Score 23-32 (n=844)
40 40
Death, MI, Stroke (%)

Death, MI, Stroke (%)

PCI/DES (N=329) PCI/DES (N=438)
30 CABG (N=340) 30 CABG (N=406)
27.2%
23.2%
20 20
17.2% 17.7%
10 10

0 0
0.0 1.0 2.0 3.0 4.0 5.0 0.0 1.0 2.0 3.0 4.0 5.0
Years Years
SYNTAX Score 33 (n=374)
40
Death, MI, Stroke (%)

PCI/DES (N=182)
CABG (N=192) 30.6%
30
PCI/DES 20
22.8% Pint=0.58
CABG
10

0
0.0 1.0 2.0 3.0 4.0 5.0
Years

Farkouh ME et al: NEJM 2012

 Limitations of SYNTAX Trial

• 1st generation DES (PES)

• Suboptimal pharmacology
• Limited use of bivalirudin
• No potent P2Y12 inhibition
• Infrequent IVUS / FFR (<10% in SYNTAX)
• Infrequent staging (14% in SYNTAX)
ARC* Stent Thrombosis to 5 Years (Per Patient)
Definite Probable Definite and Probable
10.4

2.6
1.7 1.4
1.3 1.2 0.9
0.3

(3/896) (23/893) (15/874) (11/850) (12/830) (10/803) (7/768) (76/730)

Acute Subacute Late Very Late Total

≤1d 2-30d 31-365d 366- 731- 1096- 1461- 5 year
730d 1095d 1460d 1825d

Days Postprocedure
 SCAAR Registry (94,384 pts)
Adjusted Risks of Adverse Events at 2 yrs
Restenosis Definite ST

BMS BMS

“Old DES” “Old DES”

“New DES”
“New DES”

Sarno et al, Eur Heart J 2012

PCI is Better Now than it
Was in SYNTAX and
FREEDOM!
 CABG is Gold Standard for MV CAD

• Durable procedure (at least for 5 - 10 years)

• Superior data for complex pts and Diabetics
• Complete revascularization more easily achievable
• Compliance / adherence less of an issue

So why do so many patients and physicians

still favor PCI?
Answer: (It’s not all referral bias!)
Two Very Different Procedures…
Patient Selection for Multivessel PCI
Risk Assessment Tools

• Clinical Experience
• SYNTAX Score
• “Clinical” SYNTAX Score
• Adds Age, LV function, CrCl
• Syntax II Score
Completeness of
Revascularization
Hannan EL: JACC Intv 2009; 2: 17-25
Incomplete Revascularization in DES Era
11, 294 pts (39 Hosp) in NY State PCI Registry; 69% IR

Survival
CR

IR

p=0.02

Months
Hannan EL: JACC Intv 2009; 2: 17-25
Incomplete Revascularization in DES Era
11, 294 pts in NY State PCI Registry; 69% IR

Survival Free from MI

CR

IR

p=0.02

Months

Hannan EL: JACC Intv 2009; 2: 17-25

Completeness of Revascularization

• Anatomic
• all lesions > 50%
• Functional
• Lesions producing ischemia
• Myocardial perfusion imaging
• FFR
Pijls N: JACC 2010; 56: 177-184
 FAME
1005 MVD pts having PCI with DES
RCT of FFR-guided vs angio-guided PCI
Freedom from death, MI, revasc

1.00

FFR-guided
2-year MACE
0.95 17.9% vs 22.4%
(n=509)
RR (95%CI) = 0.80 (0.62–1.02)
0.90 p=0.08
0.85 82.1%
Angio-guided
2 yrs
0.80 (n=496) 360 days ∆=4.5%
0.75 ∆=5.1% 77.6%
p=0.02 ~6% MACE/yr after 30 days!
0.70
0 120 240 360 240 600 720
Days

Pijls NHJ et al. JACC 2010;56:177–84

FAME: Adverse Events at 2 Years

Angio-guided PCI
40 FFR-guided PCI
%
p=0.07
30
22.2
p=0.03 p=0.35 p=0.03
20 17.7
p=0.25 12.7
12.3
9.7 10.4
10 8.4
6.1
3.8 2.6
0
Death MI TVR D,MI D,MI,TVR

Pijls N: JACC 2010; 56: 177-184

 2 Patients in FAME with 2VD

0.91
Patient 1

0.71 ?FFR ?FFR

0.84
Patient 2

0.57 ?FFR ?FFR

Tonino PAL et a: JACC 2010;55:2816–21
 Functional SYNTAX Score
Reclassifies > 30% of Cases

Without FFR With FFR

Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8

 PCI for Multivessel CAD
Summary

• PCI is appropriate for many pts with MV CAD

(including poor CABG candidates)
• CABG is superior for extensive, very complex CAD
• Complete revascularization is associated with
better longer-term outcomes
• Functional assessment of indeterminate lesions
improves clinical results with MV PCI
• Ischemia is key factor for PCI for stable IHD