Ajay J. Kirtane, MD, SM Center for Interventional Vascular Therapy Columbia University Medical Center / New York Presbyterian Hospital Perspectives on PCI and CABG for Multivessel Disease

Conflict of Interest Disclosure Conflict of Interest Disclosure Ajay J. Kirtane Ajay J. Kirtane  None  Off-label use will be discussed

What Are We Really Fighting? PCICABG

Newsweek 8/17/11 Except if you have prognostically important disease!

FACT… Studies of CABG (for MVD) offer some of the most compelling evidence in favor of revascularization for Stable CAD at a time when it is being severely challenged!

The Key Question… Can we extrapolate the findings from prior revascularization studies based upon CABG to PCI? (Yes, for symptoms)

Appropriateness of Revascularization and Outcomes in the UK Hemingway et al. NEJM 2001 “Studies using [the RAND] method have shown that overuse of invasive techniques in the management of coronary disease is uncommon, and attention has turned to the issue of underuse” Angina at 1 year

SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 7 SYNTAX: Generic QOL and Utilities Baseline1 month6 months12 months SF-36 Mental Component Summary P<0.001 P=0.23P= Baseline1 month6 months12 months SF-36 Mental Component Summary P<0.001 P=0.23P= Baseline1 month6 months12 months P<0.001 P=0.50P=0.07 SF-36 Physical Component Summary Baseline1 month6 months12 months P<0.001 P=0.50P=0.07 SF-36 Physical Component Summary Baseline1 month6 months12 months P<0.001 P=0.16P=0.99 EQ-5D Utilities (US) Baseline1 month6 months12 months P<0.001 P=0.16P=0.99 EQ-5D Utilities (US) PCI CABG PCI CABG Quality Adjusted Life Years  = 0.02 (P<0.01) Cohen DJ et al. NEJM 2011;364:

An nual Differences in Life Years and QALYs Time Since Randomization (Years) Δ Life Years (CABG-PCI) Δ QALYs (CABG-PCI) E. Magnuson, AHA 2012

The Key Question… Can we extrapolate the findings from prior revascularization studies based upon CABG to PCI? (Possibly, for prognosis)

CONFIRM: Association of Revascularization with All-Cause Mortality 15,223 stable patients without known CAD undergoing CTA Revascularization of “High-Risk” Anatomy (7.3%) was independently associated with 62% lower Mortality at 2.1 yrs (adjusted HR 0.38 [0.18,0.83]) Number of Vessels with Severe (>70%) Stenosis P=0.45P=0.02P=0.07 Min JK et al, Eur Heart J 2012 All-Cause Mortality at Median 2.1 years

Spontaneous MI in Trials of PCI vs. OMT Test for interaction P=0.53 Bangalore et al, Circulation Favors PCI 10 Trial PCI OMT EventIRR (95% CI)% Weight ACME-1 ACME-2 ALKK-1 AVERT DEFER MASS-1 RITA-2 SWISS Favors Medical Therapy N No Stents IRR (95% CI)EventN D+L Subtotal (I-squared = 46.3%, P=0.071) I-V Subtotal Random Effects Poisson Regression (0.13, 2.04) 0.98 (0.28, 3.39) 0.76 (0.32, 1.80) 0.92 (0.23, 3.70) 5.06 (0.24, ) 1.00 (0.20, 4.95) 1.11 (0.63, 1.95) 0.25 (0.12, 0.51) 0.72 (0.43, 1.22) 0.71 (0.50, 1.00) (0.58, 0.99) I-V Overall D+L Overall (I-squared = 31.6%, P=0.138) 0.77 (0.60, 0.99) 0.82 (0.69, 0.97) Stents D+L Subtotal (I-squared = 0.0%, P=0.556) I-V Subtotal BARI 2D COURAGE JSAP MASS (0.65, 1.33) 0.90 (0.69, 1.17) 0.43 (0.11, 1.66) 0.67 (0.39, 1.17) 0.86 (0.71, 1.05)

CV Mortality in Trials of PCI vs. OMT Test for interaction P= Favors PCI 10 Trial PCI MT Event% Weight ALKK-1 AVERT DEFER MASS-1 RITA-2 SWISS Favors Medical Therapy N No Stents IRR (95% CI)EventN D+L Subtotal (I-squared = 36.6%, P=0.162) I-V Subtotal Random Effects Poisson Regression I-V Overall D+L Overall (I-squared = 49.7%, P=0.036) Stents D+L Subtotal (I-squared = 0.0%, P=0.625) I-V Subtotal BARI 2D COURAGE JSAP MASS (0.10, 0.88) 0.92 (0.06, 14.79) 0.67 (0.11, 4.03) 2.00 (0.37, 10.92) 0.60 (0.30, 1.20) 0.15 (0.04, 0.50) 0.47 (0.24, 0.93) 0.48 (0.30, 0.77) (0.44, 1.09) 0.74 (0.49, 1.11) 0.86 (0.67, 1.11) (0.86, 2.12) 0.91 (0.52, 1.61) 0.67 (0.11, 3.99) 0.95 (0.54, 1.66) 1.08 (0.80, 1.45) IRR (95% CI) Bangalore et al, Circulation 2013

So if Revascularization of Multivessel Disease is Necessary / Desired… Which Procedure Would YOU Have?

SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 14 SYNTAX Trial Design Left Main Disease (isolated, +1, +2 or +3 vessels) N=705 3 Vessel Disease (revasc all 3 vascular territories) N=1095 De novo disease (n=1800) Limited Exclusion Criteria Previous interventions Acute MI with CPK>2x Concomitant cardiac surgery Serruys PW et al. NEJM 2009;360: Primary endpoint = death/MI/stroke/repeat revasc at 1 year

SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 15 3VD Disease 5-year Outcomes (N=1095) TAXUS (n=546) CABG (n=549) All DeathMICVARevasc. P=0.006 Patients (%) P<0.001P=0.66P< MACCE 37.5 ITT populationCumulative KM Event Rate; log-rank P value

SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 16 CABGPCIP value Death9.3%10.2%0.81 CVA3.9%1.8%0.24 MI4.9%8.8%0.20 Death, CVA or MI 14.8%17.5%0.56 Revasc.14.6%23.1%0.04 Site-reported Data; ITT populationCumulative KM Event Rate ± 1.5 SE; log-rank P value MACCE to 5 Years by SYNTAX Score Tercile 3VD Subset Low Scores Vessel Disease TAXUS (N=181) CABG (N=171) 33.3% 26.8% Months Since Allocation Cumulative Event Rate (%) P=0.21

SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 17 CABGPCIP value Death9.6%16.3%0.047 CVA3.6%2.5%0.53 MI3.1%13.8%<0.001 Death, CVA or MI 14.7%23.2%0.04 Revasc.11.0%25.1%<0.001 Site-reported Data; ITT populationCumulative KM Event Rate ± 1.5 SE; log-rank P value MACCE to 5 Years by SYNTAX Score Tercile 3VD Subset Intermediate Scores TAXUS (N=207) CABG (N=208) 22.6% 37.9% 3-Vessel Disease Months Since Allocation Cumulative Event Rate (%) P<0.001

1  Endpoint: Death, Stroke, or MI Years Death, Stroke, MI, % PCI/DES CABG P = PCI/DES CABG % 18.7% 13.0% 11.9% Farkouh ME et al. NEJM 2012 FREEDOM: 1900 pts with diabetes +MVD randomized to SES/PES vs. CABG

Death, Stroke, MI by Syntax Score Farkouh ME et al. NEJM 2012 SYNTAX Score  22 (N=669) 23.2% SYNTAX Score (N=844) SYNTAX Score  33 (N=374) P int =0.58 PCI/DES CABG Death, MI, Stroke (%) 27.2% 30.6% Death, MI, Stroke (%) Years PCI/DES (N=329) CABG (N=340) Death, MI, Stroke (%) Years PCI/DES (N=438) CABG (N=406) Years PCI/DES (N=182) CABG (N=192) % 17.7% 17.2%

What is Great about CABG (The Gold Standard for Multivessel Disease) One-stop shopping with a lasting procedure and data (both vs. PCI AND vs. OMT) in its favor! One-stop shopping with a lasting procedure and data (both vs. PCI AND vs. OMT) in its favor! Complete / Difficult revascularization is more easily achievable Complete / Difficult revascularization is more easily achievable Compliance/adherence less of an issue Compliance/adherence less of an issue Provided the patient isn’t frail, I generally feel confident with surgical risk assessment Provided the patient isn’t frail, I generally feel confident with surgical risk assessment So why do many patients and physicians still favor PCI? Answer: (It’s not all referral bias!)

Two Very Different Procedures…

Risk of Stroke with CABG vs PCI: Meta- analysis of 8 RCTs: 30-day Follow-up MASS II2/ (0.62, 15.50)6/203 GABI0/ (0.25, )2/177 BARI2/ (0.73, 17.01)7/914 ERACI 20/ (0.24, )2/225 AWESOME2/ (0.24, 8.71)3/232 ARTS 14/ (0.42, 5.32)6/605 EAST1/ (0.32, 30.01)3/ Study PCIOR (95% CI)CABG PCI worseCABG worse 4.02 (0.85, 19.03)2/5468/549SYNTAX 3VD I-squared=0% 2.62 (1.40, 4.91)13/309337/3099Fixed effects 2.62 (1.40, 4.91)Random effects0.42%1.19% ∆=0.77% Palmerini et al. JACC 2012;60:

Stroke Years Stroke, % 2.4% PCI/DES CABG P = % Severely Disabling Scale CABG PCI/DES NIH > 4 55% 27% Rankin >1 70% 60% PCI/DES CABG Farkouh ME et al. NEJM 2012 FREEDOM: 1900 pts with diabetes +MVD randomized to SES/PES vs. CABG

PCI is Better Now than it Was in SYNTAX and FREEDOM!

FAME: Primary Endpoint Tonino PAL et al. NEJM 2009;360:213–24 FFR-guided (n=509) 30 days 2.9% 90 days 3.8% 180 days 4.9% 360 days 5.1% Angio-guided (n=496) FFR assessment → PCI deferred in 37.0% of lsns Days Freedom from death, MI, revasc MACE 13.2% vs. 18.3% P= pts with MVD undergoing PCI with DES were randomized to FFR-guided vs. angio-guided intervention

Tonino et al, JACC 2010 Angiographic vs. Functional Severity of Coronary Stenosis Of 509 pts with angiographically-defined MVD, 46% had “functional MVD” FFR Stenosis classification by angiography ~20% ~35%

Myocardial Infarction Years Myocardial Infarction, % PCI/DES CABG P < % 6.0% PCI/DES CABG Farkouh ME et al. NEJM 2012 FREEDOM: 1900 pts with diabetes +MVD randomized to SES/PES vs. CABG

5-year GO and ST in SYNTAX P.W. SerruysTCT Miami, FL 22 October 2012 Slide 28 ARC * Stent Thrombosis to 5 Years (Per Patient) Days Postprocedure Acute ≤1d Subacute 2-30d Late d Very Late d d d d 10.4 Total 5 year DefiniteProbable (3/896)(23/893)(15/874)(11/850)(12/830)(10/803)(7/768) (76/730) Definite and Probable

Sarno et al, Eur Heart J 2012 SCAAR Registry (94,384 pts) SCAAR Registry (94,384 pts) Adjusted Risks of Adverse Events at 2 yrs BMS “Old DES” “New DES” RestenosisDefinite ST

Key Clinical Questions to Ask in Patients with Multivessel Disease How good a job can I (or my surgeon) really do? How good a job can I (or my surgeon) really do?  Targets, completeness of revascularization, diffuse disease, operator skill/comfort What are the goals of therapy? What are the goals of therapy? Is the patient diabetic / insulin dependent? Is the patient diabetic / insulin dependent? Can the patient adhere to DAPT? Can the patient adhere to DAPT? Is the patient at high surgical risk? Is the patient at high surgical risk?  What is the ejection fraction / is there MR?

Conclusions PCI and CABG for MVD in 2013 Multivessel disease is a high-risk and prognostically important patient scenario   “Least stable” subtype of “stable ischemic heart disease (SIHD)” (Regional) functional assessments trump angiography For true MVD, take patients off of the table to objectively assess all options Honest patient selection attuned to objective patient preference will generally dictate the best/most appropriate care!