PCI vs. CABG in Diabetic and Non-diabetic Patients with

Multivessel or Left Main DiseaseMultivessel or Left Main DiseaseNot Over till Over, PCI Is Getting Better!

Seung-Whan Lee, MD, PhDA M di l C t S l KAsan Medical Center, Seoul, Korea

Disclosure Statement of Financial Interest

I, (Seung-Whan Lee) DO NOT have a financial interest/arrangement orfinancial interest/arrangement or affiliation with one or more organizations th t ld b i d lthat could be perceived as a real or apparent conflict of interest in the context of the subject of this presentationpresentation.

Diabetic Impact on C C GPCI and CABG outcomes

Mortality after PCI Mortality after CABG

log-rank P < 0 001 log-rank P < 0 001log rank P < 0.001 log rank P < 0.001

Wilson S R et al. Dia Care 2004;27:1137-1142 Leavitt BJ et al. Circulation 2004;110:II-41-44

DM Influence on C ff &Comparative Effectiveness &

Choice of TreatmentChoice of Treatment

DMDMCABGCABG

PCIPCI

CABG vs. PCI Trials over time19901990 2000200019901990 20002000

StentsStentsGABI

BARIARTS I

DualDualantiplateletantiplatelet

BARI

EAST SOS

CABRI

RITA IERACI II

MASS II

20002000 20122012Toulouse

ARTS IIARTS II

CARDiaCARDia

SYNTAXSYNTAX

DESDES FREEDOMFREEDOM

PREPRE--COMBATCOMBAT EXCELEXCEL

BARI Trial7-Year Results By Diabetic Status

100Non Diabetic PTCA 86.8%

80

val

o abet c C 86 8%Non Diabetic CABG 86.4%

Diabetic CABG 76.4%60

Surv

iv Diabetic CABG 76.4%

Diabetic PTCA 55.7%

40

erce

nt

Treatment Comparisons20Pe

pNon-diabetics: p=0.72

Diabetics: p=0.0011

00 1 2 3 4 5 6 7 Years

The BARI Investigators. The BARI Investigators. J Am Coll Cardiol. J Am Coll Cardiol. 2000;35:2000;35:11221122--9.9.

Pooled Analysis of 10 RCTs of CABG vs PCI in Multivessel DiseaseCABG vs. PCI in Multivessel Disease

35 7812 Patients30

35 Diabetes + PCIDiabetes + PCIn=618n=618

7812 Patients (6 balloon angioplasty and 4 BMS)

25

(%)

(%)

Diabetes + CABGDiabetes + CABGn=615n=615

and 4 BMS)

15

20

rtal

ity (

rtal

ity (

10

15

Mor

Mor

No diabetesNo diabetes

0

5 CABG + PCICABG + PCIn=3298n=3298

00 1 2 3 4 5 6 7 8

Years of followYears of follow upupYears of followYears of follow--upup

HlatkyHlatky ML et al. Lancet 2009;373:1190ML et al. Lancet 2009;373:1190--7.7.

PPintint

BMS vs. CABGBMS vs. CABG 0.950.95Age Age <<62 years62 yearsAge >62 yearsAge >62 yearsBMS vs. CABGBMS vs. CABG

0.060.06MenMenWomenWomen

0 580 58

0.080.08HypertensionHypertension

No HypertensionNo Hypertension

HypercholesterolemiaHypercholesterolemia

4 4 RCTs (n=3,051), RCTs (n=3,051), 0.650.65

0.580.58HypercholesterolemiaHypercholesterolemiaNo HypercholesterolemiaNo Hypercholesterolemia

DiabetesDiabetesNo DiabetesNo Diabetes

55--year year followfollow--upupDeath, stroke or MIDeath, stroke or MI 0.840.84

No DiabetesNo Diabetes

Previous MIPrevious MINo Previous MINo Previous MI,,

0.540.54LVEF LVEF <<60%60%LVEF >60%LVEF >60%

T V l DiT V l Di

0 120 12

0.840.84Two Vessel DiseaseTwo Vessel DiseaseThree Vessel DiseaseThree Vessel Disease

PVDPVD

Favors PCIFavors PCI Favors CABGFavors CABG0.640.64

0.120.12No PVDNo PVD

All patientsAll patients

Daemon J et alDaemon J et al. . Circulation Circulation 2008;118:11462008;118:1146--11541154 Adjusted HR [95%CI] for death, stroke or MIAdjusted HR [95%CI] for death, stroke or MI

10102.02.01.01.00.50.50.10.1

Favors PCIFavors PCI Favors CABGFavors CABG

Transition from BMS to DES

ARTS II; 367 diabetic patientsH d d i (d h k MI)

60 60

Hard endpoints (death, stroke, or MI)

50

60

50

60

DiabeticsDiabetics NonNon--DiabeticsDiabetics

40 40SES vs BMS log rank P=0.03SES vs BMS log rank P=0.03SES vs CABG log rank P=0.65SES vs CABG log rank P=0.65

SES vs BMS log rank P=0.04SES vs BMS log rank P=0.04SES vs CABG log rank P=0.38SES vs CABG log rank P=0.38

20

30%%

20

30%%BMS 25.4BMS 25.4

CABG 13 5CABG 13 5BMS 16.4BMS 16.4

10

20

10

20

SES 15.5SES 15.5

CABG 17CABG 17

SES 11.9SES 11.9

CABG 13.5CABG 13.5

00 1 2 3 4 5

00 1 2 3 4 5

Time (years)Time (years) Time (years)Time (years)

Onuma Y: J Am Onuma Y: J Am CollColl Cardiol Cardiol IntvIntv 4:3174:317--23, 201123, 2011

Subgroup Analysis of Diabetes in SYNTAX(452 DM CABG 221 d TAXUS 231)

TAXUSTAXUSCABGCABG

(452 DM; CABG 221 and TAXUS 231)

11--Year MACCEYear MACCE11--Year DeathYear Death/CVA//CVA/MIMI

TAXUSTAXUSCABGCABG

26 030

35

30

35P=0.003P=0.003P=0.08P=0.08P=0.96P=0.96P=0.97P=0.97

11 Year MACCEYear MACCE11 Year DeathYear Death/CVA//CVA/MIMI

s (%

)s

(%)

26.0

20

25

30

20

25

30

Patie

nts

Patie

nts

11.814.215.1

15

20

10.3 10.115

20

PP

5

106.8 6.85

10

DMDM((nn=452)=452)

NonNon--DMDM((nn=1348)=1348)

DMDM((nn=452)=452)

NonNon--DMDM((nn=1348)=1348)

00

((nn=452)=452)((nn=1348)=1348) ((nn=452)=452)((nn=1348)=1348)

Banning A et al: JACC Banning A et al: JACC 2012;552012;55::10671067

5-Year Follow-Up of CARDia Trial510 Diabetic Patients Randomized; CABG 254 and PCI 256 (DES 69%)CABG 254 and PCI 256 (DES 69%)

Primary endpoint (death, MI, stroke)

Primary endpoint plus revascularization( ) p

P=0 11 P 0 0048P=0.11 P=0.0048

Hall R et al. 2012 ESCHall R et al. 2012 ESC

FREEDOM DesignFREEDOM Design

Eligibility:Eligibility: DM patients with MVDM patients with MV--CAD eligible for stent or surgeryCAD eligible for stent or surgeryExclude:Exclude: Patients with Patients with acute STEMI acute STEMI and and left main disease left main disease

Randomized 1:1

MVMV--StentingStenting CABGCABGWith DrugWith Drug--elutingeluting With or Without CPBWith or Without CPB

All concomitant Meds shown to be beneficial were encouraged, i l di l id l ACE i hib ARB b bl k t tiincluding: clopidogrel, ACE inhib., ARBs, b-blockers, statins

Farkouh ME, et al. N Engl J Med 2012;367:2375-84

TRIAL SCREENING & ENROLLMENTTRIAL SCREENING & ENROLLMENT

32,966 Patients were screened for eligibility

3,309 were eligible (10%)

1,409 did not consent 1,900 consented (57%)

947 Randomized to CABG18 underwent PCI/DES

26 ithd i t d

953 Randomized to PCI/DES*5 underwent CABG

3 ithd i t d 26 withdrew prior to procedure3 died prior to procedure

7 underwent neither PCI/DES orCABG

3 withdrew prior to procedure3 died prior to procedure

3 underwent neither PCI/DES orCABG

16 withdrew post-procedure43 l f ll

CABGCABG

36 withdrew post-procedure1 l f ll43 were lost to follow-up 51 were lost to follow-up

*953 and 947 included ITT analysis using all available follow-up time post-randomization

PRIMARY OUTCOME – DEATH / MI / STROKE

30 CABGPCI/DES

30

MI,

% Log rank P=0.005CABG

20St

roke

/M PCI/DES

10

Dea

th/S CABG

D

5-Year Event Rates: 26 6% vs 18 7%0

5-Year Event Rates: 26.6% vs. 18.7%

0 1 2 3 4 5 6

Years post-randomization

PCI/DES N 953 848 788 625 416 219 40PCI/DES N 953 848 788 625 416 219 40

CABG N 943 814 758 613 422 221 44

ALL-CAUSE MORTALITY

30

PCI/DESCABG30

ality

, %CABG

20

e M

orta

Logrank P=0.049

10l-Cau

se PCI/DES0 0 9

10

All

CABG

0 1 2 3 4 5

0 5-Year Event Rates: 16.3% vs. 10.9%

Years post-randomization0 1 2 3 4 5

953 897 845 685 466 243PCI/DES N 953 897 845 685 466 243PCI/DES N947 855 806 655 449 238CABG N

MYOCARDIAL INFARCTION

% PCI/DES30

ctio

n, % CABG

Logrank P<0 000120

l In

farc Logrank P<0.0001

13.9 %

10card

ia

PCI/DES6 0%

Myo

CABG

6.0%

0 1 2 3 4 5

0CABG

Years post-randomization

953 853 798 636 422 220PCI/DES N947 824 772 629 432 229CABG N

STROKE

30

Severely DisablingScale CABG PCI/DES30

%

CABG

Scale CABG PCI/DES

NIH > 4 55% 27%R ki 1 70% 60%

20

roke

, % PCI/DESRankin >1 70% 60%

10

Str

Logrank P=0.034

2 4%

CABG 5.2%

Y t d i ti0 1 2 3 4 5

0 PCI/DES 2.4%

Years post-randomization

953 891 833 673 460 241PCI/DES N

947 844 791 640 439 230CABG N

REPEAT REVASCULARIZATION30

n, %

PCI/DESCABG

20rizat

ion

Log rank P<0.000120

ascu

lar

13%

10t R

eva

PCI/DES

13%

Rep

eat

CABG

5%

0

R CABG

0 1 2 3 4 5 6 7 8 9 10 11 12

Months post-procedure944 88 8 6 818 92PCI/DES N944 887 856 818 792PCI/DES N911 858 836 825 806CABG N

SUBGROUP ANALYSESTreatment x Subgroup 5-yr Rate (%)CABG PCI/DES Treatment x Subgroup

Interaction5-yr Rate (%)

PCI/DES CABGCABGWorse

PCI/DESWorse

ALL SUBJECTS 1900SYNTAX 22 669

27 1923 17

P=0.58

P=0.46

SYNTAX 22 669SYNTAX 23-32 844SYNTAX 33 374

Males 1356Females 544

23 1727 1831 2327 1826 21P 0.46

P=0.55

P=0 75

Females 544Caucasian 1452

African-American 1192-Vessel Disease 3143 V l Di 1573

26 2127 1924 1622 1127 20P=0.75

P=0.37

3-Vessel Disease 1573LVEF < 40% 32LVEF 40% 1259

No LAD involved 151

27 2062 3123 1823 18P=0.83

P=0.57

No LAD involved 151LAD involved 1737

Hx stroke 65No Hx stroke 1835

23 1827 1959 3525 18

P=0.62

P=0.99

Renal insuff. 129No Renal insuff. 1771

HbA1c < 7% 630HbA1c 7% 1119

44 3725 1723 1628 20

P=0.049N. American Site 770Non-N. American 1130

28 1625 21

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Hazard Ratio for Death/Stroke/MI

VA CARDS Trial

Initial Planned Sample Size; N=790

J J AmAm Coll Coll CardiolCardiol 2013;612013;61:808:808––1616

Initial Planned Sample Size; N=790

Death or MI rate;Death or MI rate; CABG = PCI

Death rate;Death rate; CABG < PCI

MI tMI rate; CABG > PCI

Observational Studiesbeyond RCTbeyond RCT

ASCERT studyCER on Revascularization Strategy;

NCDR an STS database (65 years or older; 86 244 CABG & 103 549 PCI)86,244 CABG & 103,549 PCI)

WeintraubWeintraub WS WS eet al; t al; N N EnglEngl J Med. J Med. 2012;366:2012;366:14671467--76.76.

WeintraubWeintraub WS WS eet al; t al; N N EnglEngl J Med. J Med. 2012;366:2012;366:14671467--76.76.

A Pooled Analysis of 3 Registry (5775 Individual Patient Data)

MAINCOMPARE ASAN-Multivessel ASAN-MAIN

(5775 Individual Patient Data)

Registry Registry Registry

Study type Multi-center, observation

Single-center, observation

Single-center, observationy yp observation observation observation

# of patients PCI 1102CABG 1138

PCI 1547CABG 1495

PCI 276CABG 469

Target subjects Left main Multivessel Left main

Age 62 63 61

Male 72% 71% 72%

Diabetes 32% 29% 32%Duration (median) 5.2 years 5.6 years 7.5 years

NEJM Circulation

Publications 2008;358:1781-92JACC

2010;56:117–124

2008;117:2079-86JACC

2011;57:128-37

JACC 2010;56:1366–75

Park DW et al; Park DW et al; Circ Circ Cardiovasc Interv. 2012;5:467Cardiovasc Interv. 2012;5:467--475475

Adjusted OutcomesSubjects HR 95% CI P-value Interaction P

(DM vs. NON-DM)Death

Non-DM 1.15 0.88-1.50 0.39 0.27DM 1.15 0.88-1.51 0.30

DM, insulin 0.88 0.48-1.62 0.68DM, non-insulin 0.89 0.58-1.39 0.61

Death Q-MI StrokeDeath, Q-MI, StrokeNon-DM 0.99 0.78-1.26 0.96 0.97DM 1.00 0.79-1.26 0.97

DM, insulin 0.89 0.51-1.56 0.68DM, non-insulin 1.05 0.70-1.58 0.81

R t l i tiRepeat revascularization Non-DM 3.55 2.61-4.83 <0.001 0.08DM 3.56 2.62-4.83 <0.001DM 3.56 2.62 4.83 0.001

DM, insulin 6.42 2.83-14.53 <0.001DM, non-insulin 5.71 3.50-9.31 <0.001

Park DW et al; Park DW et al; Circ Circ Cardiovasc Interv. 2012;5:467Cardiovasc Interv. 2012;5:467--475475

MAIN-COMPARE Registry ; DM and Left Main Revascularization; DM and Left Main Revascularization

Kim WJ et al; Kim WJ et al; J J AmAm Coll Coll CardiolCardiol IntvIntv 2009;2:9562009;2:956––6363

PRECOMBAT findings according to DM

Park SJ et al; Park SJ et al; J J AmAm Coll Coll CardiolCardiol IntvIntv 2009;2:9562009;2:956––6363

SYNTAX trial3 Y t i Di b ti P ti t A di3-Year outcomes in Diabetic Patients According

to SYNTAX score

3-Year death/MI/CVA/Revasc 3-Year death/MI/CVA

P=0.98 P=0.04

P<0.001

P 0 08 P 0 67

P=0.03

P=0.08 P=0.67

Score ≤ 22(n=136)

Score ≥32(n=157)

Score 23-32(n=156)

Score ≤ 22(n=136)

Score ≥32(n=157)

Score 23-32(n=156)

PCICABG Ann Thorac Surg 2011;92:2140–6

SORT OUT IV

MACE MICardiac death

Definite ST Definite or probable STTVR

Circulation. 2012;125:1246-1255

SORT OUT IV

Circulation. 2012;125:1246-1255

Summaryy

• For diabetic patients with MVD and/or LM• For diabetic patients with MVD and/or LM disease, several small-sized RCT and

b ti l t di h d fli tiobservational studies showed conflicting results comparing PCI with first-generation DES and CABG.

• As a landmark RCT in diabetic population, compelling evidence from the FREEDOM trial showed a superiority of CABG with lower p ymortality and fewer MI, but more strokes.

Summary

• As compared with first-generation DES, p g ,second- and newer-generation DES has shown better efficacy and safety outcomesshown better efficacy and safety outcomes.

• Further studies are still required (1) to evaluate comparative effectiveness of newer DES andcomparative effectiveness of newer DES and CABG in DM and (2) to assess whether DM it lf i k bl i l f t i l tiitself is a remarkably crucial factor in selecting CABG instead of PCI regardless of lesion complexity.