2012 Top 10 Advances of Interventional Cardiology:

Prediction for the decade

Samin K Sharma, MD, FACC, FSCAI Director Clinical & Interventional Cardiology Zena and Michael a Weiner Professor of Medicine Mount Sinai Hospital, NY

Intervention 2012
Andreas Gruentzig 1939 1985 father of angioplasty
His dream was the catheter-based percutaneous treatment of vascular disease in alert, awake patients

NY State: Annual Revascularization Volume: 2003-2007-08-11 PCI CABG PCI vs. CABG
70000 60000 50000

58178

59976

11.3% 53223 54542 55258 54865 50124 8.9%

50046
40000

51677

N
30000 20000 10000 0

14692

12988 11884

11124

7.2% 10324 9985 2008 9812 2009 9742 2010 9845 2011

2003

2004

2005

2006

2007 YEAR

2012 Top 10 Advances of Interventional Cardiology Studies selected from the following journals
Journals 2012 New Engl J Med JAMA / (Lancet) Circulation J Am Coll Cardiol/JACC Intervention ACCi2 meeting abstracts AHA meeting abstracts TCT meeting abstracts
# articles related to PCI

20 5 (3) 68 72 112 45 22

324

2012 Top 10 Advances of Interventional Cardiology

Reasons for selection of the study

Revolutionary / significant observation Widespread acceptance Change in clinical practice

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

TRILOGY ACS STUDY DESIGN

Medically Managed UA/NSTEMI Patients Randomization Stratified by: Age, Country, Prior Clopidogrel Treatment
(Primary analysis cohort Age < 75 years)
Medical Management Decision < 72 hrs. (No prior clopidogrel given 4% of total) Medical Management Decision < 10 days (Clopidogrel started < 72 hrs. in hospital OR on chronic clopidogrel) 96% of total
Median Time to Enrollment = 4.5 Days

Clopidogrel1
300 mg LD + 75 mg MD

Prasugrel1
30 mg LD + 5 or 10 mg MD

Clopidogrel1
75 mg MD

Prasugrel1
5 or 10 mg MD

Minimum Rx Duration: 6 months; Maximum Rx Duration: 30 months

Primary Efficacy Endpoint: CV Death, MI, Stroke

1. All patients were on aspirin and low-dose aspirin (<100 mg) was strongly recommended. For patients < 60 Kg or >75 years, 5 mg MD or prasugrel was given.

TRIOLOGY Trial: Efficacy Endpoint and TIMI Major Bleeding Through 30 Months
(Overall population) 20
20.3% Primary

Clopidogrel HR (95% CI): 0.96 (0.86, 1.07) P = 0.45

Prasugrel

18.7% Endpoint

Efficacy

15 Endpoint

10

HR (95% CI): 1.23 (0.84, 1.81) P = 0.29

2.5 % TIMI 1.8 % Bleeding

Major

0 0 180 360 540

Days

900 720 Roe et al., NEJM 2012:367:1297

Trilogy ACS: Primary Efficacy Endpoint and TIMI Major Bleeding Through 30 Months (Age <75 years; N=7243)
Prasugrel Clopidogrel

Endpoint (%)

HR (95% Cl): 0.91 (0.79, 1.05) p=0.21

16.0% Primary Efficacy 13.9% Endpoint

HR (95% Cl): 1.31 (0.81, 2.11) p=0.27 TIMI 2.1% Major 1.5% Bleeding

Days

Roe et al., NEJM 2012:367:1297

Trilogy ACS Trial: Incidence of Outcomes by Angiography Status

Prasugrel Clopidogrel

Angio (n=3085)
p=0.031

p=0.954

No Angio (n=4158)

p=0.042

p=0.989

%
p=0.626 p=0.074

p=0.569

p=0.851

Primary Endpoint

MI

CV Death

TIMI Major Bleeding

Primary Endpoint

MI

CV Death

TIMI Major Bleeding

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. 5. 6. 7. 8. 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10. TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

Percutaneous LV Assist Devices

IABP PTVA: TandemHeart IMPELLA: Recovers 2.5

PROTECT II Trial Design

Hemodynamic support during high-risk, non-emergent PCI, N=654 Unprotected LM or last patent conduit & EF<35% or 3VD & EF<30% Assess Myocardium at Jeopardy and Indicate all stenosis considered for stenting

IABP + PCI

R 1:1

IMPELLA + PCI

Primary Endpoint = MAE at 30-days

3 Month Follow-up; MAE at 90-days

ONeill W et al. ACCi2 2011.

LV Support During High Risk PCI

Recent Trials Using IABP
BCIS-1 CRISP AMI IABP-SHOCK II

Balloon-pump Assisted Coronary Intervention Study: BCIS-1

Kaplan Meier 6 month mortality
No planned (n=150)

Elective IABP (n=151)

7.4% vs 4.6%, p = 0.32

Perera D et al. JAMA 2010;304:867.

IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP-AMI Randomized Trial Anterior STEMI Without Shock
Randomize Open Label IABP prior to PCI (n ~ 300 ) At least 12 hours of IABP post PCI
Inclusion Criteria Anterior STEMI 2 mm in 2 contiguous leads or at least 4 mm in the anterior leads Planned Primary PCI within 6 hr

Standard of Care Primary PCI alone

Routine Post PCI care

Cardiac MRI performed day 3-5 post PCI Primary Endpoint: Infarct Size on CMR All Patients with CMR data Patients with Prox LAD occlusion TIMI 0/1 flow Clinical Events 6 months Patel et al. JAMA 2011;306:1329

1. 2.

IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP-AMI Randomized Trial
All (N=337) IABP+PCI (N=161) PCI Alone (N=176) P Value

Primary endpoint Infarct size (% LV), modified ITT all patients with CMR data N 275 133 Mean 39.8 42.1 Median 38.8 42.8

0.060 142 37.5 36.2 0.110

Infarct size (%LV), modified ITT patients prox. LAD and TIMI flow 0/1 N 192 93 99 Mean 44.4 46.7 42.3 Median 42.1 45.1 38.6

Patel et al. JAMA 2011;306:1329

IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP-AMI Randomized Trial
30-day Clinical Events
IABP+PCI (N=161) Death (%) Stroke (%) Major bleed per GUSTO 1 definition or transfusion (%) Vascular complications (%) Major limb ischemia requiring operative intervention (n) Distal embolization (n) Major dissection (n) Pseudoaneurysm or AV fistula (n) Hematoma > 5 cm (n) * From KM curves and log-rank test. 1.9* 1.9 3.1 4.3 0 0 2 3 3 PCI Alone (N=176) 4.0* 0.6 1.7 1.1 0 0 0 2 0 P Value 0.26* 0.35 0.49 0.09

Patel et al. JAMA 2011;306:1329

IABP-Shock II Trial: Guidelines

IABP in AMI complicated by Cardiogenic Shock

Class IC

Class IB

IABP-SHOCK II Flow Chart

Patient in cardiogenic shock complicating AMI Check inclusion and exclusion criteria Not suitable Informed consent Randomization IABP-SHOCK II Registry

Group 1 (n = 301) IABP + Optimal medical therapy

288 received IABP 13 did not receive IABP 10 died before IABP 3 protocol violation

Group 2 (n = 299) No IABP + Optimal medical therapy

Allocation
269 received control therapy 30 cross-over to IABP (22 first day, 8 day 1-8 ) 4 mechanical complications 25 protocol violation, 1 unclear reason 299 intended early revascularization 288 primary PCI 3 primary CABG 8 no revascularization 298 with 30-day follow-up - 1 withdrew informed consent

301 intended early revascularization 287 primary PCI 3 primary CABG 11 no revascularization 300 with 30-day follow - 1 lost to follow up

Revascularization

Follow-Up

300 primary endpoint analysis

Primary endpoint analysis

298 primary endpoint analysis

Thiele H et al. Am Heart J 2012;163:938

IABP-Shock II Trial: Results Primary Study Endpoint: 30-day Mortality

Mortality (%)

P=0.92 by log-rank test Relative risk 0.96; 95% CI 0.79-1.17; P=0.69 by Chi2-Test

Time After Randomization (Days)

Thiele H et al. NEJM 2012;367:1287.

IABP-Shock II Trial: Results

Safety
IABP (n=300) All-cause mortality 30-D; n (%) Stroke in-hospital; n (%) Gusto bleeding: lifethreatening/severe; n (%) Gusto bleeding: moderate; n (%) Re-infarction in hospital; n (%) Stent thrombosis in-hospital; n (%) Peripheral ischemic complication requiring intervention; n (%) Sepsis; n (%) 119 (39.7) 2 (0.7) 10 (3.3) 52 (17.3) 9 (3.0) 4 (1.3) Control (n=298) 123 (41.3) 5 (1.7) 13 (4.4) 49 (16.4) 4 (1.3) 3 (1.0) P 0.69 0.28 0.51 0.77 0.16 0.71

13 (4.3) 47 (15.7)

10 (3.4) 61 (20.5)

0.53 0.15

Thiele H et al. NEJM 2012;367:1287.

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. 5. 6. 7. 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

GRAVITAS Study Design

Elective or Urgent PCI with DES*
VerifyNow P2Y12 Test 12-24 hours post-PCI by Accumetrics
PRU 230

R
High-Dose Clopidogrel
clopidogrel 600-mg, then clopidogrel 150-mg daily X 6 months

Standard-Dose Clopidogrel
clopidogrel 75-mg daily X 6 months

Primary Efficacy Endpoint: CV Death, Non-Fatal MI, Stent Thrombosis at 6 mo Key Safety Endpoint: GUSTO Moderate or Severe Bleeding at 6 mo Pharmacodynamics: Repeat VerifyNow P2Y12 at 1 and 6 months
*Peri-PCI clopidogrel per protocol-mandated criteria to ensure steady-state at 12-24 hrs
placebo-controlled

All patients received aspirin (81-162mg daily)

Price et al. JAMA 2011;305:1097.

GRAVITAS Trial: Primary Endpoint: CV Death, MI, Stent 4 Thrombosis

Cumulative Incidence of CV death, non-fatal MI, or ST %

2.3% vs. 2.3% HR 1.01 (95% CI 0.58 1.76) p=0.98

High-Dose Clopidogrel Standard-Dose Clopidogrel

0
No. at Risk
High Dose Clopidogrel Standard Dose Clopidogrel

30
1109 1105

60
1056 1057

90
1029 1028

120
1017 1020

150
1007 1015 998 1005

180
747 773

210
54 53

Observed event rates are listed; P value by log rank test.

Price et al. JAMA 2011;305:1097.

TRIGGER PCI Trial: Study Design

Elective PCI with DES without GP IIb/IIIa use
VerifyNow P2Y12 Test 2-4hrs first clopidogrel MD (75mg)

N= 2150
PRU 206
All patients received aspirin (81-162mg daily)

R
Prasugrel
Loading dose 60mg, then 10mg daily X 6 months

Placebo LD,then Clopidogrel 75mg

daily X 6 months

Primary Efficacy Endpoint: CV Death, Non-Fatal MI at 6 mo Key Safety Endpoint: Moderate or Severe Bleeding at 6 mo Pharmacodynamics: Repeat VerifyNow P2Y12 at 3 and 6 months

Trial was halted after 432 pts enrolled because of <2% event rate (projected 7%) in 250 pts reaching 6M mark

TRIGGER-PCI Study
Cumulative Composite Incidence of Efficacy PAI Data Bleeding Events

Trenk et al., JACC 2012;59:2159

ARCTIC Trial:
Randomization before planned PCI with DES (n = 2500)

Monitoring Treatment Arm 1- Systematic assessment of PD response to clopidogrel + aspirin pre-DES and between day 14 and day 30 2-Adjustment of DAPT dose regimen* if high ontreatment platelet reactivity pre-DES 3-Adjustment of DAPT dose regimen if hyper/hyporesponder during the maintenance phase

Conventional Arm 1- No monitoring of PD response 2- DAPT strategy at physician discretion according to routine practice

Assessment of the primary endpoint at 1 year (minimal follow-up of 6 months for the last patients) All-cause mortality MI All urgent revascularization Stent thrombosis requiring revascularization or not Ischemic stroke requiring a new hospitalization
DAPT =dual antiplatelet therapy *In the absence of high platelet reactivity (HPR), MD regimen is aspirin 75 mg + clopidogrel 75 mg.

ARCTIC Monitoring Arm

VerifyNow before PCI: aspirin and P2Y12 thienopyridine

ARU >550 Reload with 500 mg of IV aspirin

< 15% inhibition/PRU > 235

GP IIb/IIIa + clopidogrel (re)-loading (> 600 mg) or prasugrel 60 mg and 150-mg MD clopidogrel or prasugrel 10 mg+

VerifyNow DAY 14-30: aspirin and P2Y 12 thienopyridine for all patients

ARU >550

< 15% inhibition/PRU > 235

> 90% inhibition

Double aspirin

Clopidogrel dose by > 75 mg or switch to prasugrel 10 mg+

If clopidogrel 150 mg to 75 mg, or if prasugrerl switch to clopidogrel 75 mg

ARCTIC Trial: Monitoring Antiplatelet Therapy for Coronary Stenting

Proportion of Patients with Primary Outcome Events and with Main Secondary Outcome Events at 1 Year Follow-up

Collett et al., NEJM 2012:367:2100.

ARCTIC Trial: Monitoring Antiplatelet Therapy for Coronary Stenting

Study End Points at 1 Year Follow-up*
Conventional Treatment (n=1227)
p = 0.10 p = 0.32

Monitoring (n=1213)

%
p = 0.28 p = 0.77 p = 0.24 p = 0.51 p = 0.76 p = 0.08

Primary End Point

Secondary Death Death End Point recurrent ACS,

stroke, TIA

MI

Stent Urgent thrombosis revasc

Major or Minor bleeding

* Patients could have more than one end point

Collett et al., NEJM 2012:367:2100.

Routine Testing for Platelet Inhibition by VerifyNow Assay Instrument (Accumetrics)

Assessment of platelet aggregation inhibition (PI): - Goal; Optimal response PRU <230 in maintenance phase on chronic ADP receptor blockers ?PRU 208 - Management if PRU >230; - Make sure about compliance - PPI interaction - ? Genetic testing for 2C19*2 allele polymorphism - If on plavix, then either switch to Prasugrel (30mg LD & 5-10mg MD or double plavix dose to 150mg daily)

GIFT Study: (Genotype Information and Functional Testing) Study GRAVITAS Trial

Price et al., JACC 2012;59:1928

GIFT Trial: Change in On-Treatment Reactivity From Randomization to 30 Days by CYP2C19 Genotype and Treatment Group

Price et al., JACC 2012;59:1928

GIFT Trial: Adjusted Odds Ratios for High OTR at 30 Days and 6 Months by CYP2C19 Genotype According to MD Assignment

High on treatment platelet reactivity is predicted by genetic makeup but any genetic phenotype did not correlate with the 6M MACE

Price et al., JACC 2012;59:1928

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. 5. 6. 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

Does Aggressive Statin Therapy Reduce Coronary Atherosclerotic Plaque Lipid Content? Results From: Reduction in YELlow Plaque by Aggressive Lipid LOWering Therapy (YELLOW) Trial
Annapoorna S Kini, PR Moreno, J Kovacic, A Limaye, ZA Ali, J Sweeny, U Baber, R Mehran, G Dangas, SK Sharma

Cardiac Catheterization Laboratory Mount Sinai Heart Mount Sinai Hospital, NY, NY
Presented at ACC 2012; Accepted for Publication in JACC 2013

Near Infrared Spectroscopy (NIRS)

NIRS provides lipid contents based on the spectra processed by algorithm and shown as lipid core burden index; LCBI (range 1~1000) for each region of interest.
Proximal

Chemogram Block Chemogram

Wire Detection

Landmark

Hypothesis

High-Dose statin therapy will reduce lipid core content in severely obstructive coronary lesions in the short term (6-8 weeks), as evaluated by Nearinfrared Spectroscopy

Primary outcome Change in coronary lipid core burden index (LCBI) after short-term high-dose statin therapy, as determined by Near-infrared Spectroscopy (NIRS)

Two/Three Vessel CAD (n= 87)

After stenting the target vessel The non-target lesion underwent FFR FFR0.8 IVUS, NIRS

Randomized Standard n = 43 Continue statin the patient was taking Dual antiplatelet therapy for 1 year Aggressive n = 44 Rosuvastatin 40 mg daily Dual antiplatelet therapy for 1 year

Follow up Cath (6-8 weeks) FFR, IVUS and NIRS repeated. If FFR 0.8, lesion stented and imaging repeated. If FFR > 0.8 the patient was treated medically Imaging data analyzed by CRF Core Lab Data analysis for primary outcome analyzed by MSH independent Core Lab
*Optimal medical therapy for all patients

Paired Analysis Lesion LCBI

P = 0.47 P = 0.0008
Baseline Follow-up

400

LCBI

200

Absolute LCBI Reduction 33

Standard

Aggressive

Case Example
Lesion LCBI: 259

Baseline

Max10mm LCBI: 511 Max4mm LCBI: 802

Plaque Area 5.6mm2

FFR: 0.74
Lesion LCBI: 177 Max10mm LCBI: 289 Max4mm LCBI: 474

Follow-up

Plaque Area 5.5mm2

FFR: 0.78

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. 5. 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

Prior Meta-analysis of 23 RCTs of Radial vs. Femoral PCI (N=7020)

Major bleeding/Vascular Comp Death Death, MI or stroke PCI Procedure Failure Access Site Crossover 1.0 0.27 (0.16-0.45) 0.74 (0.42-1.30) 0.71 (0.49-1.01) 1.31 (0.87-1.96) 3.82 (2.83-5.15)

Radial better

Femoral better

Jolly S, et al. Am Heart J 2009;157:132

RIVAL (RadIal Vs femorAL access for

PCI) Study Design
NSTE-ACS and STEMI (n=7021)
3831 (45%) pts were sub-study of OASIS-7 Trial

Key Inclusion: Intact dual circulation of hand required Interventionalist experienced with both (minimum 50 radial procedures in last year)

Randomization
Radial Access (n=3507) Femoral Access (n=3514)

Blinded Adjudication of Outcomes Primary Outcome: Death, MI, stroke or non-CABG-related Major Bleeding at 30 days
Jolly S et al. Lancet 2011;377:1409.

RIVAL TRIAL
Secondary Outcomes at 30 days
8

Radial (n=3507) Femoral (n=3514)

%
6

p=0.90
4

p=0.65 p=0.47 3.2 p=0.23 1.3 0.7 0.9 0.6 0.4 1.5 1.9 p=0.30

3.2
2

1.7

0
Death, MI, Stroke

Non-CABG Major Bleeding

Death

MI

Stroke

Jolly S et al. Lancet 2011;377:1409.

RIVAL Study: Subgroups: Primary Outcome

Death, MI, Stroke or non-CABG major Bleed
Overall Age <75 75 Gender Female Male BMI <25 25-35 >35 Radial PCI Volume by Operator 70 70-142.5 >142.5 Radial PCI Volume by Centre Lowest Tertile Middle Tertile Highest Tertile Diagnosis at presentation NSTE-ACS STEMI
0.25

Hazard Ratio (95% CI)

p-value Interaction 0.786 0.356 0.637 0.536

0.021

0.025

Jolly S et al. Lancet 2011;377:1409.

1.00

4.00

Radial better

Femoral better

RIFLE STEACS Flow Chart

DESGN: Prospective, randomized (1:1), parallel group, multi-center trial INCLUSION CRITERIA: all ST Elevation Myocardial Infarction (STEM) eligible for primary percutaneous coronary intervention. ESCLUSION CRITERIA: contraindication to any of both percutaneous arterial access, INR > 2.0.
Romagnoli E at al. JACC 2012

RIFLE STEACS Trial: Results NACE rate

Fermoral arm (N=501) 25 Radial arm (N=500)

Mortality:
p = 0.003 21.0

9.2%

5.2%

p=0.02

20

p = 0.029 15 13.6 11.4 10 7.2 5

p = 0.026 12.2 7.8

0
NACE MACCE Bleedings

Romagnoli E at al. JACC 2012

Transradial PCI in AMI: REAL Multicenter Registry Clinical Outcomes in the Propensity Score-Matched at 2Y
Transradial Group (n = 1501) 20 15 % 10 5 0 All Cause Death MI Stroke All Cause Death/ Major Bleeding/ MI/Stroke Vascular Events Valgimigli et al., JACC Interv 2012;5:23. Transfermoral Group (n= 1501) P = 0.013 17.7 P = 0.025 11.4 8.8 P = 0.27 5.7 6.9 P = 0.45 1.2 1.7 P = 0.20 5.8 4.8 13.9

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. 5. DAPT Duration Trials: PRODIGY, RESET 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10. TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

(Very) Late stent thrombosis

DES: Factors to consider
Discontinuation of antiplatelet therapy

Delayed endothelialization

Late Stent Thrombosis

Late incomplete apposition

Polymer hypersensitivity/ inflammation

Optimal Duration of ADP Receptor Blockers Post DES Still Remain Unclear (Aspirin 81-325 mg daily for life)
AHA/ACC Updated Guidelines 2006

Cypher Stent Launch CURE, PCI-CURE 2001 5/2003 CREDO 2002 9-12 months

AHA/ACC/SCAI Updated Guidelines 2005 (TAXUS stent 6 months post PCI) (Cypher stent 3 months post PCI)
(FDA recommendations)

BMS Era

DES Era

AHA/ACC PCI Guidelines 2001

(1-12 months post BMS)

TAXUS Stent ESC 2005/ACC 2006 Launch PCI Updated Guidelines 3/2004
(12 months post PCI)

Clopido/Prasugrel/Ticag should be continued for 1 yr or even longer if no contraindications

If not sure about DAPT compliance or has to be interrupted in 12M then BMS (Basket late) is safer & should be preferred

Stent Thrombosis Rates (ARC Definite)

SORT-OUT IV LESSON I COMPARE
2.7
P<0.001

RESOLUTE-AC

SPIRIT IV

P=0.01

P=0.008

1.6

P=0.01

P=0.002

1.2 1.2 0.5 0.2

XIENCE CYPHER V XIENCE CYPHER V XIENCE TAXUS V Liberte

1.3

0.6 0.3
XIENCE RESOLUTE V

0.3
XIENCE TAXUS V

9 Months

3 Years

2 Years

1 Year

1 Year

REAL LATE/ZEST LATE Trials: 12M vs. 24M of Dual Antiplatelet Therapy
5

p=0.05
4

12 Month Regimen (n=1357) 24 Month Regimen (n=1344)

p=0.22

3.2
%
3

3.1
p=0.24

2.4

1.8 1.4

1.6

p=0.49

0.7 0.8

p=0.76

0.4 0.4
0

p=0.35

0.1 0.2
TLR TIMI Major Bleeding

MI, Stroke or death

Death

MI

Definite ST

N Engl J med 2010;362:1374.

PRODIGY Trial: 6M vs. 24M of Dual Antiplatelet Therapy

70 % second generation DES (Xience V/ Promus/ Endeavor) ST 15 6M (N = 1012) 1.0% 24M (N = 1001) 0.9% p= NS
10

10.0 10.1

p= NS 9.6 8.9

p= 0.0002 7.4

%
5

p= 0.041 1.6 0.6

0

3.5

Primary end point Death/ MI/ Stroke

Death / MI

TIMI Major Bleeding

Type 2, 3 or 5 BARC bleeding

Valgimigli M et al. Circulation 2012;125:2015.

RESET Trial: Clinical Outcomes Through 1 Year

p = 0.84
5 4.7 4.7

E-ZES + 3 Month DAPT (n=1059) Standard Therapy (n=1058)

p = 0.70 3.9 3.7

p = 0.39 1.0 0.5 p = 0.41 0.2 MI 0.4 TVR p = 0.65 0.2 0.3

p = 0.20 1.0 0.5

0 Primary End Point Death Stent Major or minor thrombosis bleeding

Kim et al., JACC 2012:60:1340

DAPT DURATION POST DES

Therefore DAPT duration of 6M is now becoming the new 12M with newer generation DES

What about DAPT discontinuation POST DES?

Xience V USA Registry: Late ST Rates (30 D 1 Year)

After DAPT Interruption

Subsequent Late ST (ARC Def/Prob) (%)
2

Overall Standard (Low) Risk

1.5

0.49
0.5

0.37 0.16 0
13/3500 2/1272 2/435 0/157

0.26 0
1/378 0/147

0/292 0/120

No Interruption

Interruption After 30 Days

Interruption After 90 Days

Interruption After 180 Days

Krucoff, Hermiller, Sharma et al. JACC Intervent 2011;4:1298.

Proposed Management of Patients Requiring Temporary DAPT Cessation: MSH Protocol

Emergent need for surgery <2 weeks BMS, <6-12 months DES Non-emergent, non-deferrable need for surgery

Cypher/Taxus DES DAPT minimum 12M Xience V/Endeavor DES DAPT minimum 6M

-Admit & stop clopidogrel/prasugrel -Proceed with surgery -Platelet transfusion usually given (5-10 units) -Continue aspirin in all cases except specific neurosurgical indications -Consider s/c enoxaparin or IV GP IIb/IIIa inhibitor
Restart clopidogrel post-op

<2 weeks BMS <6-12 months DES

>2 weeks BMS >6-12 months DES

-Stop clopidogrel/pras -Stop clopidogrel/pras -Admit on day 3 HR cases -Admit on day 5 -Surgery on day 5+ -Consider enoxaparin/GPI -Surgery on day 5+

Restart clopidogrel at day 7+

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. 4. DES Comparison Trials: RESOLUTE, PLATINUM 5. DAPT Duration Trials: PRODIGY, RESET 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

Drug Eluting Stent System:

First vs. Second Generation New Stent Designs
XIENCE V PROMUS Drug
Stent Material Bare Strut Thickness Bare Strut Thickness Polymer Thickness Total Thickness

ENDEAVOR

TAXUS EXPRESS LIBERTE Paclitaxel

Stainless Steel 0.0052

CYPHER

Everolimus
Cobalt Chromium 0.0032

Zotarolimus
Cobalt Chromium 0.0036

Sirolimus
Stainless Steel 0.0055

81m 7 m
88m

91m 6 m
97m

132m 16m
148m

140m 14m
154m

Scanning Electron Micrographs of 14-Day Comparator DES and BMS Controls

Endothelial Cell Recovery Between Comparator Polymer-Based Drug-Eluting Stents

Scanning Electron Micrographs of 28-Day Comparator DES and BMS Controls

The upper panels show corresponding radiographic images of each stent. The lumens are clearly patent and struts are easily discerned underneath a thin neointimal surface. Among DES, there is less endothelial cell surface coverage in SES and PES stents compared with ZES and EES. The panel insets are representative images at higher magnification (200) from proximal and distal regions showing bare struts, surface thrombi, inflammatory cells, and endothelial cells.

The upper panels show corresponding radiographic images of each stent. The lumens are patent and struts are less discernable under a thicker neointima relative to 14-day stents. Overall endothelial coverage is near complete in all DES although it remains poor above struts in PES and SES compared with ZES and EES. The panel insets are at higher magnification (200) from the proximal and distal regions and show persistent uncovered struts, surface thrombi, inflammatory cells, and endothelial cells.

Joner et al. J Am Coll Cardiol 2008;52:333

SPIRIT IV: Ischemia-Driven TLR Through

2 Years
Ischemia-driven TLR (%)
XIENCE V (n=2458) TAXUS (n=1229)
HR [95%CI] = 0.54 [0.38, 0.78] p=0.0007 4.6% 2.2% 2.4%

HR [95%CI] = 0.66 [0.50, 0.88] p=0.004

6.9% 2.4% 4.5%

Number at risk XIENCE V TAXUS 2458 1229 2419 1186 2392 1159 2350 1140

Months
2318 1124 2291 1112 2269 1104 2246 1093 2226 1073

Stone et al. JACC 2011;58:19.

Comparison of Everolimus-Eluting Vs. PaclitaxelEluting Stents in Real-life Practice: COMPARE Trial

Major Adverse Cardiac Events
Paclitaxel-Eluting Stent (n=903) Everolimus Stent (n=897)
10

p=0.02 9.0

p=0.0001 p=0.007 6.0 6.0 p=0.002 3.0 2.0 0.7 3.0 5.0 p=0.58 2.0 2.0

%
4 2

Death

MI

TVR

MACE

Stent Thrombosis

Kedi E et al. Lancet 2010; 375:201.

Resolute All Comers Trial

Clinical Outcomes at 24 Months
Zotarolimus-Eluting Stent (n=1119) Resolute DES Everolimus-Eluting Stent (n=1126) XienceV DES
15

p=0.75

12

p=0.52
10.0 9.1

12.5 12.9

%
6 3

p=0.57 p=0.36
4.0 3.2 1.9 1.0 5.5 5.0

p=0.07

Death

MI

TVR

MACE

Stent Thrombosis Definite/Probable

Silber et al., thelancet. 2011;377:1241

PLATINUM Trial: 1-Year Clinical Outcomes

P=0.97

%
P=0.25 P=0.85

P=0.72 P=0.83

P=1.00

Stone et al., JACC 2011;57:1700

Overview of Bioresorbable Stents

Company
Igaki-Tamai (2000)

Picture

Polymer/Drug
PLLA PLLA plus Tranilast

Features
Zig-zag design deployed with a heated balloon

Biotronik (2006) Abbott (BVS) (2006) Reva Medical (2008) BTI (2008)

Mg alloy

Balloon expandable design

PLLA with everolimus

Balloon expandable

Tyrosine poly carbonate with iodine radio-opacity Salicylic acid blended into polymer

Design has ratchet links for deployment Balloon expandable

Abbott Bioabsorbable Stent (BVS) ABSORB Trial

Bioabsorbable Stent Technology

At 2 yrs FU:

progressive polymer degradation normal histopathologic healing restored vasoreactivity late positive remodeling Serruys et al. Lancet 2009

ABSORB B Group 1 & 2 Clinical Results - Intent to treat

30 days Non-Hierarchical Cardiac Death% Myocardial Infarction % (n) Q-wave MI Non Q-wave MI Ischemia driven TLR % (n) CABG PCI Hierarchical MACE % (n)
*one patient missed the 2-year FUP

6 months N= 101 0 3.0 (3) 0 3.0 (3) 2.0 (2) 0 2.0 (2) 5.0 (5)

1 Year N=101 0 3.0 (3) 0 3.0 (3) 4.0 (4) 0 4.0 (4) 6.9 (7)

2 Years N=100* 0 3.0 (3) 0 3.0 (3) 6.0 (6) 0 6.0 (6) 9.0 (9)

N=101 0 2.0 (2) 0 2.0 (2) 0 0 0 2.0 (2)

No scaffold thrombosis by ARC or Protocol out to 2-Year Only 2 additional TLR events between 1 year and 2 years
MACE: Cardiac death, MI, ischemia-driven TLR TVF: Cardiac death, MI, ischemia-driven TLR, ischemia-driven TVR
SE2936417 Rev. A Absorb BVS is neither approved nor available for sale in the U.S. Note: Absorb BVS is currently CE marked. Information provided for educational purposes only.

Drug Eluting Stents Comparison:RCT

(Scale of 1+Bad to 4+Best)
Cypher Taxus Resolute/E

Xience/Promus

Efficacy TLR MI Death Safety Early stent thrombosis Late stent thrombosis Crossability/Trackability Market Share (%)

++++ -

+++ + <5

+ ++ -/+ ++ ++++ 10-20

++++ ++ ++ +++ ++++

68-78

Therefore Clopidogrel duration may safely be reduced to 6-12M with 2nd generation DES

2012 Top 10 Advances of Interventional Cardiology 1. 2. 3. SYNTAX Trial: 5-Year follow-up 4. DES Comparison Trials: RESOLUTE, PLATINUM 5. DAPT Duration Trials: PRODIGY, RESET 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

SYNTAX Trial
Eligible Patients
Syntax Objective: To compare the MACCE rate at 12 months between patients treated with TAXUS 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 left main + 3-vessel disease

3-vessel disease
Revascularization in all 3 vascular territories

Serruys P et al. NEJM 2009;360:961.

SYNTAX Trial: All-Cause Death/CVA/MI to 5 Years

CABG (N=897) Cumulative Event Rate (%)
Before 1 year* 7.7% vs 7.6% P=0.98 1-2 years* 2.2% vs 3.5% P=0.11

TAXUS (N=903)
2-3 years* 2.5% vs 3.8% P=0.14 3-4 years* 2.7% vs 4.6% P=0.051 4-5 years* 3.1% vs 3.1% P=0.98

50

P=0.03 P=0.03
25 20.8%

16.7% 0 0 12 24 36 Months Since Allocation 48 60

ITT population

SYNTAX Trial: Repeat Revascularization to 5 Years

CABG (N=897) Cumulative Event Rate (%)
Before 1 year* 5.9% vs 13.5% P<0.001 1-2 years* 3.7% vs 5.6% P=0.06

TAXUS (N=903)
2-3 years* 2.5% vs 3.4% P=0.33 3-4 years* 1.6% vs 4.2% P=0.002 4-5 years* 1.9% vs 4.3% P=0.008

50

P<0.001 P=0.001
25.9% 25 13.7%

0 0 12

Cumulative KM Event Rate

1.5 SE; log-rank P value; Binary rates

*

24 36 Months Since Allocation

48

60
ITT population

SYNTAX Trial: MACCE to 5 Years

CABG (N=897)
Before 1 year*

TAXUS (N=903)
2-3 years* 4.8% vs 6.7% P=0.10 3-4 years* 4.2% vs 7.9% P=0.002 4-5 years* 5.0% vs 6.3% P=0.27

Cumulative Event Rate (%)

12.4% vs 17.8%

50

P=0.002

1-2 years* 5.7% vs 8.3% P=0.03

P<0.001 P<0.001
25

37.3%

26.9%

0 0 12

Cumulative KM Event Rate

1.5 SE; log-rank P value; Binary rates

*

24 36 Months Since Allocation

48

60
ITT population

 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: MACCE vs. SYNTAX Score

*P= 0.03 vs PCI with SYNTAX score 22 P= 0.002 vs PCI with SYNTAX score 23-32 Trend for PCI: P=0.006

P < 0.001
25

MACCE at 12 Months (%)

CABG (n= 897) TAXUS (n= 903)

16.7

23.4*

20 15 10 5 0

14.7

13.6

12.0 10.9

22

23-32 SYNTAX Score

33

Serruys P et al. NEJM 2009;360:961.

SYNTAX Trial:MACCE to 5 Years by SYNTAX Score Tercile Low Scores (0-22)

CABG (N=275) TAXUS (N=299) Overall
50

CABG Death 10.1% 4.0% 4.2%

PCI 8.9% 1.8% 7.8% 16.1% 23.0%

P value 0.64 0.11 0.11 0.81 0.06

Cumulative Event Rate (%)

P=0.43

32.1%

CVA MI

25

28.6%

0 0 12 24 36 48 60

Death, CVA or 14.9% MI

Months Since Allocation

Cumulative KM Event Rate

1.5 SE; log-rank P value

Revasc 16.9%

SYNTAX Trial:MACCE to 5 Years by SYNTAX Score Tercile Intermediate Scores (23-32)

CABG (N=300) TAXUS (N=310) Overall
50

CABG Death CVA MI

25.8%

PCI 13.8% 2.0% 11.2% 20.7% 24.1%

P value 0.68 0.25 <0.001 0.42 <0.001

12.7% 3.6% 3.6%

Cumulative Event Rate (%)

36.0%

P=0.008

25

0 0 12 24 36 48 60

Death, CVA or 18.0% MI

Months Since Allocation

Revasc 12.7%

Cumulative KM Event Rate

1.5 SE; log-rank P value

SYNTAX Trial:MACCE to 5 Years by SYNTAX Score Tercile High Scores (33)

CABG (N=315) TAXUS (N=290) Overall
50

CABG Death CVA MI

26.8%

PCI 19.2% 3.5% 10.1%

P value 0.005 0.80 0.004 0.007 <0.001

11.4% 3.7% 3.9%

Cumulative Event Rate (%)

P<0.001
44.0%

25

0 0 12 24 36 48 60

Death, CVA or 17.1% 26.1% MI

Months Since Allocation

Revasc 12.1% 30.9%

Cumulative KM Event Rate

1.5 SE; log-rank P value

ACCF/AHA/SCAI Guidelines 2011: UPLM Revascularization to Improve Survival

Revasc Method
CABG PCI

COR
I IIaFor 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%) IIbFor 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%) III: HarmFor SIHD in patients (versus performing CABG) with unfavorable anatomy for PCI and who are good candidates for CABG IIaFor UA/NSTEMI if not a CABG candidate IIaFor STEMI when distal coronary flow is <TIMI grade 3 and PCI can be performed more rapidly and safely than CABG

LOE
B B

B B C

GNL 2011

Method of Revascularization of Multi-vessel and LM Coronary Artery disease

CABG PCI

Two-vessel CAD with proximal LAD stenosis Three Vessel CAD with low CAD burden (i.e., three focal stenosis, low SYNTAX score) Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, presence of CTO, or high SYNTAX score >32). Isolated left main stenosis Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33) 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 A A A A A

A A U U U I

Patel et al., JACC 2012; 59:0000

As you all know, since Jan 2010, we have incorporated Syntax score in stratifying patients for revascularization choices (PCI or CABG) for advanced CAD and pts with Syntax score 33 who are not high-surgical risk, being preferentially referred for CABG. This practice is further endorsed by the recent presentation of 3-year data of Syntax Trial at TCT 2010, showing CABG arm having significantly lower individual endpoint of death or MI or revascularization versus Taxus DES PCI, in these high Syntax score pts. Hence as per evidence-based guidelines, optimal coronary revascularization to high Syntax score pts should be CABG. Therefore, patients with SYNTAX Score 33 and not having absolute contraindications to CABG (included below), should be taken out of the cath room for discussion regarding choices of revascularization. As a rule, these patients (SYNTAX Score 23) should be categorically recommended for CABG because of survival & MI advantage over PCI. An opinion of a cardiac surgeon will be required if PCI is contemplated in these pts. Only exception to this rule (taking the pt out of the cath room for discussion) could be, if the referring cardiologist (who has to be different then the Interventionalist) is physically present in the cath lab and expresses strong desire against CABG (because of his/her own belief or known wishes of the patient).

Update in the incorporation of SYNTAX Score (23) for revascularization choices in patients with extensive CAD

Patients with SYNTAX Score >22 but following situations and co-morbidities could be excluded from routine CT surgery consultations: 1) 2) 3) 4) 5) 6) Acute MI (STEMI or Non-STEMI) Age >80 years old Prior CVA/recent TIA Severe COPD (FEV1 <1L) and on chronic bronchodilator therapy BMI >50 Participation in IRB approved trial of PCI

Also patients firm refusal for CABG should be entertained only after the CT surgery consultation outside the cath room in the holding area or the telemetry unit. We will continue to monitor and report the data of this system process going forward by analyzing the triage of all CAD pts with Syntax score of (23).

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 CABG XIENCE Prime stent 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.

2012 Top 10 Advances of Interventional Cardiology 1. 2. FAME II Trial: PCI vs. MMT 3. SYNTAX Trial: 5-Year follow-up 4. DES Comparison Trials: RESOLUTE, PLATINUM 5. DAPT Duration Trials: PRODIGY, RESET 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

FAME II Trial: Flow Chart

Stable patients scheduled for 1, 2 or 3 vessel DES stenting FFR in all targets lesions

Randomized Trial
At least 1 stenosis with FFR < 0.80 Randomization 1:1 OMT PCI + OMT OMT

Registry
When all FFR >0.80

50 % randomly assigned to FU

Follow-up after 1 and 6 months and then 1, 2, 3, 4 and 5 years

FAME II Trial: Cumulative Incidence of Primary End Points and Its Components

Bruyne et al., NEJM 2012:367:991

FAME II Trial Results

FFR-Guided PCI (n=447) Primary Endpoint Death Myocardial Infarction Urgent Revascularization Free from Angina (1 month) 4.3% 0.2% 3.4% 1.6% 71% MT (n=441) 12.7% 0.7% 3.2% 11.1% 48% p value <0.001 0.31 0.89 <0.001 <0.001

De Bruyne, et al., NEJM 2012:367:991.

FAME II Trial: Revascularization Status

25 P<0.001 19.5 20 MT Alone (n=441) PCI+MT (n=447) Registry (n=166)
5.2% MT alone and 0.9% PCI patients had MI or UA with ECG changes requiring TVR (HR 0.13; P=<0.001)

15

P<0.001 11.1

10

P<0.001 8.6

(%)

3.1

3.6 1.6 2.4 1.6 1.2

0 Any Revascularization Urgent Revascurization Non-Urgent Revascurizaton Bruyne et al., NEJM 2012:367:991

Page 991

Conclusions In patients with stable coronary artery disease and functionally significant stenosis, FFRguided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to favorable with the best available medical therapy alone. (Funded by St. Jude Medical; Clinic al trials. Gov. number. NCT 01132495)

2012 Top 10 Advances of Interventional Cardiology 1. FREEDOM Trial: CABG vs. PCI in MV diabetes 2. FAME II Trial: PCI vs. MMT 3. SYNTAX Trial: 5-Year follow-up 4. DES Comparison Trials: RESOLUTE, PLATINUM 5. DAPT Duration Trials: PRODIGY, RESET 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

FREEDOM Trial: TRIAL SCREENING & ENROLLMENT

32,966 Patients were screened for eligibility 3,309 were eligible (10%) 1,409 did not consent 1,900 consented (57%)

953 Randomized to PCI/DES* 947 Randomized to CABG*

5 underwent CABG 3 withdrew prior to procedure 3 died prior to procedure 3 underwent neither PCI/DES or CABG 16 withdrew post-procedure 43 were lost to follow-up 18 underwent PCI/DES 26 withdrew prior to procedure 3 died prior to procedure 7 underwent neither PCI/DES or CABG 36 withdrew post-procedure 51 were lost to follow-up

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

FREEDOM Trial: PRIMARY OUTCOME DEATH / STROKE / MI

PCI/DES CABG Logrank P=0.005 PCI/DES CABG
10

Death/Stroke/MI %

30

20

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

0 1 2 3 4 5 6

Years post-randomization
PCI/DES N CABG N 953 947 848 814 788 758 625 613 416 422 219 221 40 44

FREEDOM Trial: ALL-CAUSE MORTALITY

All-Cause Mortality %
PCI/DES CABG

30

20

Logrank P=0.049 PCI/DES

10

CABG
0

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

0 1 2 3 4 5

Years post-randomization
PCI/DES N CABG N 953 947 897 855 845 806 685 655 466 449 243 238

FREEDOM Trial: MYOCARDIAL INFARCTION

Myocardial Infarction %
PCI/DES CABG

30

Logrank P<0.0001
20

13.9 %
PCI/DES
10

6.0%
CABG

Years post-randomization
PCI/DES N 953 CABG N 947 853 824 798 772 636 629 422 432 220 229

FREEDOM Trial: STROKE

30

Severely Disabling Scale CABG PCI/DES

NIH > 4 55% Rankin >1 70%

Stroke %

20

27% 60%

CABG PCI/DES

Logrank P=0.034
10

CABG
0

5.2%
2.4%
4 5

PCI/DES
0 1 2 3

Years post-randomization
PCI/DES N CABG N 953 947 891 844 833 791 673 640 460 439 241 230

FREEDOM Trial: REPEAT REVASCULARIZATION

30

Repeat Revascularization, %

PCI/DES CABG

Log rank P<0.0001

20

13%
10

PCI/DES 5% CABG

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

Months post-procedure
PCI/DES N 944 CABG N 911 887 858 856 836 818 825 792 806

FREEDOM Trial: PRIMARY ENDPOINT DEATH/STROKE/MI TREATMENT / SYNTAX INTERACTION: p=0.58

Freedom from Event (%)
100 90 80 70 60 50 40 30 20 10 0 0.0

Freedom from Event (%)

SYNTAX Score 22 (N=669)

5-Year Event Rates:

SYNTAX Score 23-32 (N=844)

100 90 80 70 60 50 40 30 20 10 0 0.0

23.2% 17.2%
PCI/DES CABG

5-Year Event Rates:

27.2% 17.7%
PCI/DES CABG

1.0

2.0

3.0

4.0

5.0

1.0

2.0

3.0

4.0

5.0

Years post-randomization Freedom from Event (%)

Years post-randomization

SYNTAX Score 33 (N=374)

100 90 80 70 60 50 40 30 20 10 0 0.0

5-Year Event Rates:

30.6% 22.8%
PCI/DES CABG

Years post-randomization 1.0 2.0 3.0 4.0

5.0

Conclusions
In patients with diabetes and advanced coronary disease, CABG was of significant benefit as compared to PCI. MI & all cause mortality were independently decreased, while stroke was slightly increased There was no significant interaction between the treatment effect of CABG on the primary endpoint according to SYNTAX score or any other prespecified subgroup. CABG surgery is the preferred method of revascularization for patients with diabetes & multi-vessel CAD.

2012 Top 10 Advances of Interventional Cardiology 1. FREEDOM Trial: CABG vs. PCI in MV diabetes 2. FAME II Trial: PCI vs. MMT 3. SYNTAX Trial: 5-Year follow-up 4. DES Comparison Trials: RESOLUTE, PLATINUM 5. DAPT Duration Trials: PRODIGY, RESET 6. Transradial Intervention in STEMI: RIFLE-STEACS 7. YELLOW Trial: Change in plaque composition 8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC 9. IABP Trials: CRISP-AMI, IABP-SHOCK II 10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS

2012 Top 10 Advances of Interventional Cardiology

Reasons for selection of the articles

Revolutionary / significant observation Widespread acceptance Change in clinical practice
IABP, PI Testing, Prasugrel in ACS: Infraredex, Xience V: DAPT 6M, TRI in STEMI:

FREEDOM, FAME II, Syntax Scoring:

Final result BETTER INTERVENTION/SURVIVAL

#1: New Standards of Safety of Coronary Interventions (PCI)

MSH:Temporal Trends in Complications of PCI

0.8

2007 (n= 4422) 2008 (n= 4594) 2009 (n= 5078) 2010 (n= 4799) 2011 (n= 4707)

Over 5 years with <0.21% mortality in all comers ...<0.52% major complications ...<0.04% urgent transfer to OR has established PCI as a safe & effective strategy
0.58 0.52 0.53 0.51 0.49

0.6

%
0.4
0.27

0.24 0.16

0.2

0.23 0.21 0.11 0.06 0.08 0.04 0.0 0.0 0.09 0.08

0.08 0.09

In-hospital death

Urgent CABG

Q-wave/Large MI

Major Complications (death, rCABG, MI, CVA)

NYS-DOH Report of PCI 2008-10

Data on Top 10 Volume Centers in NY State 30-Day RAMR
PCI Statistics 2008-10 1. Mount Sinai Hospital
2. Saint Francis Hospital 3. Columbia Presbyterians H 4. Lenox Hill Hospital 5. Saint Josephs Hospital 6. North Shore Hospital 7. LIJ Medical Center 8. Rochester General Hospital 9. Stony Brook Hospital 10. Beth Israel Medical Ctr # cases All cases Non-Emergency cases Emergency cases

14414
9045 8750 8504 6510 6112 5896 5801 5335 5073

0.64**
0.61** 0.87 0.81 0.83 0.70 0.63 1.29* 0.98 0.65

0.41**
0.35** 0.59 0.47 0.58 0.56 0.36 0.77* 0.58 0.30**

2.55
2.74 2.36 3.24 2.57 1.72** 2.45 4.33 3.48 3.70

NYS Total
http://www.nyhealth.gov

162918

0.90

0.55

3.17

**RAMR significantly lower, *RAMR significantly higher than statewide rate

NYS-DOH Report of PCI 2010

Data on Top 10 Volume Centers in NY State 30-Day RAMR
PCI Statistics for 2010 1. Mount Sinai Hospital
2. Saint Francis Hospital 3. Columbia Presbyterians H 4. Lenox Hill Hospital 5. St Josephs Hospital 6. LIJ Medical Center 7. Stony Brook Hospital 8. Beth Israel Medical Ctr 9. Rochester General Hospital 10. North Shore Hospital # cases All cases Non-Emergency cases Emergency cases

4777
2936 2856 2740 2314 2019 1762 1762 1899 1850

0.57
0.74 0.81 0.71 0.86 0.84 0.93 0.75 0.95 0.78

0.36
0.48 0.55 0.40 0.61 0.63 0.52 0.40 0.73 0.56

2.55
2.74 2.36 3.75 2.88 2.07 3.78 3.89 2.50 2.32

NYS Total
http://www.nyhealth.gov

54035

0.84

0.51

3.09

Conclusions For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infraction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinincalTrials.gov number, NCT00086450.)