SHA24/063004

Unprotected Left Main Intervention: EXCEL Trial Samin K. Sharma, MD, FACC, FSCAI Director, Clinical and Interventional Cardiology Zena & Michael Wiener Professor of Medicine President Mount Sinai Heart Network Dean International Clinical Affiliation Mount Sinai Heart , New York Disclosure/COI: Speaker Bureau for Abbott, BSC, DSI, TMC, Abiomed

Complexity of PCI-treated Patients has Historically Increased with Time

Complexity

Left Main Three Vessels-DM CTO >1 Bifurcation Two Vessels Small Vessels Long Lesions Single Vessel Time

CABG PCI

Today

Appropriateness Criteria: Method of Revascularization of Advanced CAD CABG

PCI

No diabetes & normal LVEF

Diabetes

Depressed LVEF

No diabetes & normal LVEF

Diabetes

Depressed LVEF

Two Vessel Coronary Disease+ Proximal LAD Stenosis

A A

A A

A A

A A

A A

Three Vessel Coronary Disease

A A

A A

A A

A A U U

UU

U U

A

A A

A A

A A

A A

A A

I I

I I

II I

Isolated Left Main stenosis Isolated Left Main and additional Coronary artery disease

Patel MR et al. J Am Coll Cardiol. 2009;53(6):530-553

EXCEL Trial (Evaluation of Xience Prime vs CABG for Examination of LM Disease) LM disease (±1, 2 or 3 vessel disease) and a SYNTAX score of ≤32 Randomize 2600 pts

XIENCE® V/Prime stent ®ABBOTT Vascular

CABG

• The primary endpoint is the composite incidence of death, MI or stroke at a median FU duration of 3 years, powered for sequential non-inferiority and superiority testing.

• The major secondary endpoint is the composite incidence of death, MI, stroke or unplanned repeat revascularization. All patients will be followed for 5 years total.

LMCA Stenosis Location

LMCA

D LA

26% Ostium

X C L 66% Bifurcation

8% Body-Shaft

About two third of LMCA Lesions include distal bifurcation

Issues in PCI (DES) of ULMCA Stenosis • Procedural

success

• Acute complications / stent thrombosis • Restenosis / TLR • Sudden death • Long-term follow-up vs. CABG

Meta-analysis of PCI of Unprotected LMCA BMS Clinical Setting MI/UA

F/U

(mths)

Cardiac death (%)

Restenosi s (%)

MACE (%)

107

91 / 16

15±8

10.6

22

30/80

1998

42

All elective

10±5

0

22

19

Karam et al.

1998

39

36 / 3

24±7

15.4

5

20

Kosuga et al.

1999

107

83 / 24

35

11.2

40

22

Wong et al.

1999

55

All elective

16±10

1.8

20

18

Silvestri et al.

2000

140

All elective

12

8.7

23

28

Kosuga et al.

2001

101

86 / 15

34

5.9

20

38

Lee et al.

2001

13

All elective

18±3

7.7

23

38

Park et al.

2001

127

All elective

12±11

0.9

12

13

Tan et al.

2001

279

Various

19

20.2

25

35

Takagi et al.

2002

67

Various

31±23

11.9

24

34

Sharma et al.

2002

200

Various

15±8

6

12

18

16 ±12

9.1

22

26

Author

Year

N

ULTIMA (Ellis)

1997

Park et al.

Total

1077

DES for the Unprotected LMCA Park

Chieffo

Valgimigli

Lee

Price

Migliorini

Erglis

(1)

(2)

(3)

(4)

(5)

(6)

(7)

Patients (n)

102

85

95

50

50

101

53

Distal location (%)

71

81

65

60

94

87

81

0

3.5

11

4

2

11

2

84.3

NR

NR

42

98

96

100

Angiographic resten (%)

7*

19*

NR

NR

44‥

16*

6*

TLR or TVR (%)

2

18.8

6.3

13

38

14

2

Cardiac mortality12 m(%) Angiographic F/U (%)

3. Circulation 4.4% & TLR2005;111:1383; of 11.2% 4. JACC 2006;47:864; 5. JACC 2006;47:871; 6. CCI 2006;68:225; 7. JACC 2007;50:491 (half of the BMS trials) 1.

JACC 2005;45:351;

2. Average Circulation 2005;111:791; Mortality

DES in Non-Bifurcation Unprotected LMCA MACE at Hospitalization and at Long-Term Clinical FU (N = 147)

Event-Free at 1400 days

In-Hospital (N = 147) CI 92.6%

Cardiac death (%)

Follow-Up (886±308 D)

0

2.7

89%

Death in 60 high-risk pts (%)

0

6.6

CI

Death in 87 low-risk pts (%)

0

0

TLR (%)

0.7

0.7

TVR (%)

0.7

4.7

MACE (%)

4.0

7.4

886 Days

MACE at 886±308 days occurred in 11 pts (7.4%);the dashed lines represent the 95% CIs

High-risk pts were defined as EuroSCORE ≥6 and/or Parsonet ≥13 and/or prior bypass surgery with failure of all conduits.

Chieffo et al, Circulation 2007;116:158.

A Randomized Comparison of PES vs. BMS for Treatment of Unprotected LMCA Stenosis 6-Months Cumulative Outcomes: All had CB and IVUS BMS (n = 50) PES (n = 53) P Value Total death (%)

2

2

>0.99

MI (%)

14

9

0.548

TLR (%)

16

2

0.014

MACE (%)

30

13

0.054

Angiographic resteno (%)

22

6

0.021

IVUS neointimal volume (mm3)

26 ± 22

17 ± 17

0.014

Erglis et al. J Am Coll Cardiol 2007;50:491

PCI (DES) vs. CABG for ULMCA Lesion • Observational Data: - Main-Compare by Park - Cedars-Sinai data by Lee - Multicenter data by Chieffo - Bolognese registry data

• Randomized Trials - LE MANS Trial - SYNTAX Trial (LM subset) - PRECOMBAT Trial

PCI vs. CABG for ULM Disease: Bologna Registry Clinical Outcomes at Median FU of 430 days CABG (n=154) PCI (n=157)

30

25.5

25

20

P = NS

30

P = 0.0001

DES (n=94)

25

P = NS

20

%

% 15

12.3

13.4

15

0

10

8.3

10

4.5

5

Mortality

12.5

11.7

MI

5.3 2.6 TLR

5

0

Mortality

MI

TLR

Palmerini et al. Am J Cardiol 2006;98:54

MAIN-COMPARE Registry: Stents versus CABG for Left Main Coronary Artery Disease KMDEATH Curves for LM Matched for Propensity Scores for DES or CABG DEATH, Q-wave MI or STROKE (N= 396 pairs) 96.9 95.9 93.1 94.9 95.9

93.6

94.9

91.0 DES CABG

P = 0.26

P = 0.26

TVR

93.9 91.7

92.0 88.5

DES CABG

P = 0.16

P = 0.16

99.5

98.4

98.4

93.8

92.3

90.7

P <0.0001 DES CABG

Seung et al. New Engl J Med 2008;358:1781

LE MANS Trial 1-Yr Outcomes After PCI vs. CABG for ULM Intervention PCI (n=52)

CABG (n=59)

P

2

13

0.03

1- yr MACCE-Free Survival (%)

71.2

75.5

0.29

In-stent restenosis (%)

9.6

-

-

Stent thrombosis (%)

0

-

-

Change in LVEF (%)

3.3 ± 6.7

0.5 ± 0.8

0.047

Outcome

30-day MACCE (%)

Kahn et al. J Am Coll Cardiol 2008

PRECOMBAT Trial: DES vs. CABG ULMCA Disease Cumulative Incidence of the Primary End Point of MACE or CVA

Cumulative Incidence of Death from Any Cause, MI, or Stroke

Park S published online at NEJM.org April 4, 2011

PRECOMBAT Trial: DES vs. CABG ULMCA Disease

Clinical End Points 24 Mo after Randomization 18

PCI n=300 CABG n=300

16

p=0.12 14 12

12.2

p=0.02

% 10 8

8.1

p=0.45

6

4.4 4.7

4

3.4 2.4

2 0

9.0

p=0.83

MACE

Death/ MI/ Death Stroke

p=0.49

4.2

p=0.25

p=0.56 1.7

MI

1.0

1.4

0.4 0.7

Stroke

0.3

TVR

ST

Park S published online at NEJM.org April 4, 2011

SYNTAX Trial Eligible Patients

Syntax Objective: To compare the MACCE rate at 12 months between patients treated with TAXUS速 stents vs. patients undergoing CABG for de novo 3VD and/or LM disease. (*MACCE = major adverse cardiac and cerebrovascular events; defined as death, stroke, MI, or repeat revascularization)

De novo disease Isolated left main Limited Exclusion Criteria Previous interventions (PCI or CABG) Acute MI with CPK>2x Concomitant valve surgery

left main + 1-vessel disease left main + 2-vessel disease

3-vessel disease Revascularization in all 3 vascular territories

left main + 3-vessel disease Serruys P et al. NEJM 2009;360:961.

SYNTAX Trial: Left Main and 3 V CAD Subgroup MACCE Rates at 12 Months

25

20

CABG Taxus

19.8

15.8 15

13.7

13.2

% 10

14.4

8.5

7.1

19.3

19.2

15.4 11.5

7.5

5

0

All LM N=705

LM Isolated N=91

LM+1VD N=138

LM+2VD N=218

LM+3VD N=258

3VD ( w/o LM) N=1095

Serruys PW et al. N Engl J Med 2009;360:961-72.

• SYNTAX score is purely an anatomic score of the extent of CAD (>50%) in a pt • Each lesion is assigned a numerical number and then sum of all lesions score for a patient is calculated to come up with the final numerical SYNTAX score • Pt are divided in 3 groups: Low <22 Intermediate 23-32

High >32 Serruys P et al. NEJM 2009;360:961.

SYNTAX Trial LM Subgroup:

MACCE in Relation to SYNTAX Score 30

CABG TAXUS

P = .008 25.3

MACCE at 12 Months (%)

25 20 15

P = .19

P = .54 15.5

13.0

10

12.6

12.9

7.7

5 0

N=103

≤22

N=118

N=92

N=195

23-32 SYNTAX Score

N=150 N=135

≥33

Serruys PW et al. N Engl J Med 2009;360:961-72.

MACCE to 5 Years by SYNTAX Score Tercile LM Subset Low Scores 0-22 CABG (N=104) TAXUS (N=118) Cumulative Event Rate (%)

LM Disease 50

CABG

PCI

P

Death

11.3%

7.0%

0.28

CVA

4.1%

1.8%

0.28

MI

3.1%

6.2%

0.32

Death, CVA or 15.2% MI

13.9%

0.71

Revasc 20.3%

23.0%

0.65

P=0.74 31.5% 30.4%

25

0 0

12

24

36

48

Months Since Allocation

60

MACCE to 5 Years by SYNTAX Score Tercile LM Subset Intermediate Scores 23-32 CABG (N=92) TAXUS (N=103) LM Disease Cumulative Event Rate (%)

50

CABG

PCI

P

Death

19.3%

8.9%

0.04

CVA

3.6%

1.0%

0.23

MI

4.6%

6.0%

0.71

Death, CVA or 24.9% 15.7% MI

0.11

Revasc 16.6% 22.2%

0.40

P=0.88 32.7% 32.3%

25

0 0

12

24

36

48

Months Since Allocation

60

MACCE to 5 Years by SYNTAX Score Tercile LM Subset High Scores â&#x2030;Ľ33

CABG (N=149) TAXUS (N=135) LM Disease Cumulative Event Rate (%)

50

29.7% 25

0 12

24

36

Death

PCI

P

14.1% 20.9%

0.11

CVA

4.9%

1.6%

0.13

MI

6.1%

11.7%

0.13

Death, CVA or 22.1% 26.1% MI

0.40

46.5%

P=0.003

0

CABG

48

Months Since Allocation

60

Revasc 11.6% 34.1% <0.001

Clinical Case #2: Complex Intervention for Non-STEMI and Mild Hypotension • 73 yrs old male patient with Non-STEMI and BP 86/60mmHg • History: HTN, NIDMM, Hyperlipidemia, Angina/SOB on exertion with (+) MPS suggestive of LAD ischemia • Medication: ASA, Clopidogrel, Metformin, IV Dopamine • Cath: LVEDP normal, LVEF 25% III vessel CAD LM disease No aortic stenosis • Planned Impella assisted high risk PCI of LM/LAD/LCx using Rotational atherectomy for LAD and CB PTCA for LCx followed by DES and SKS for dLM lesion

Clinical Case #2: Complex Intervention for Non-STEMI and Mild Hypotension • 73 yrs old male patient with Non-STEMI and BP 86/60mmHg • History: HTN, NIDMM, Hyperlipidemia, Angina/SOB on exertion with (+) MPS suggestive of LAD ischemia • Medication: ASA, Clopidogrel, Metformin, IV Dopamine • Cath: LVEDP normal, LVEF 25% III vessel CAD LM disease No aortic stenosis

• Successful intervention of: RA 1.75mm burr and LMDistal (Xience 3.5/18), LAD-mid (Xience 3/33) and 2.75mm Flextome and then LCx-prox (Xience3/18), LCx-OM2 (Xience 2.75/28)

2011 ACCF/AHA/SCAI Guideline for Coronary Revascularization: Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery JACC. 2011:58;2550.

GNL 2011

ACCF/AHA/SCAI Guidelines 2011: UPLM Revascularization to Improve Survival Revasc Method CABG PCI

COR I IIaFor SIHD when low risk of PCI complications and high likelihood of good long-term outcome (e.g., SYNTAX score of ≤22, ostial or trunk left main CAD), and a signficantly increased CABG risk (e.g., STS-predicted risk of operative mortality ≥5%)

LOE B B

IIbFor SIHD when low to intermediate risk of PCI complications and intermediate to high likelihood of good long-term outcome (e.g., SYNTAX score of <33, bifurcation left main CAD) and increased CABG risk (e.g., moderate-severe COPD, disability from prior stroke, prior cardiac surgery, STS-predicted operative mortality >2%)

B

III: HarmFor SIHD in patients (versus performing CABG) with unfavorable anatomy for PCI and who are good candidates for CABG

B

IIaFor UA/NSTEMI if not a CABG candidate IIaFor STEMI when distal coronary flow is <TIMI grade 3 and PCI can be performed more rapidly and safely than CABG

B C

GNL 2011

Method of Revascularization of Multi-vessel and LM Coronary Artery Disease CABG

PCI

Two-vessel CAD with proximal LAD stenosis

A

A

Three Vessel CAD with low CAD burden (i.e., three focal stenosis, low SYNTAX score)

A

A

Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, CTO, or high SYNTAX score >32)

A

U

Isolated left main stenosis

A

U

Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33)

A

U

Left main stenosis and additional CAD with intermediate to high CAD burden (i.e., three vessel involvement, presence of CTO, or high SYNTAX score >32)

A

I

Patel et al., JACC 2012; 59:0000

European Guidelines

ACCF/AHA/SCAI Guidelines for Coronary Revascularization 2011:

Heart Team Approach to UPLM or Complex CAD

GNL 2011

Proposed Approach to LM PCI Sign LCX

Crush or T stenting

Kissing stents

50% Insign or small LCX

Single across LCX Small LM

Single across LCX 4 mm

Large LM

LM Bifurcation Lesion: Two Stent Approach An approach for bifurcation lesions when using 2 stents as intention to treat Bifurcation lesion with no disease proximal to the bifurcation or very short proximal lesion

SKS/VSTENT

Bifurcation lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 900 angle

T- STENT Culotte

Bifurcation lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 600 angle

SHORTMINI Crush

EXCEL Trial (Evaluation of Xience Prime vs. CABG for Examination of LM Disease) LM disease (±1, 2 or 3 vessel disease) and a SYNTAX score of ≤32 Randomize 2600 pts

ABBOTT Vascular XIENCE Prime stent

CABG

• The primary endpoint is the composite incidence of death, large MI or stroke at a median FU duration of 3 years, powered for sequential non-inferiority and superiority testing.

• The major secondary endpoint is the composite incidence of death, MI, stroke or unplanned repeat revascularization. All patients will be followed for 5 years total.

16TH AUNNUAL LIVE SYMPOSIUM June 12-15,2013

Take Home Message:

Techniques of LM Stenting with Circulatory Support  Many studies have shown the feasability and safety of LM stenting with DES and MACE outcomes upto 3 yrs remains equal to CABG in the majority  Optimal technique, strategy, stent deployment and positioning remain crucial in this setting  In many patients a single stent cross-over has shown excellent long-term results