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2012 Top 10 Advances of InterventionalCardiology:

Prediction for the decade

Samin K Sharma, MD, FACC, FSCAIDirector Clinical & Interventional Cardiology

Zena and Michael a Weiner Professor of Medicine

Mount Sinai Hospital, NY


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Intervention 2012Andreas Gruentzig

1939 1985father of angioplasty

His dream was thecatheter-based

percutaneous treatment

of vascular disease inalert, awake patients


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NY State: Annual Revascularization Volume:

2003-2007-08-11PCI vs. CABG

N

5004651677

5817859976

53223

1469212988

11884 10324

11124

2003 2004 2005 2006 2007 2008 2009 2010 2011

70000

60000

50000

40000

30000

20000

10000

0

YEAR

PCICABG

11.3%

7.2%

54542

9985

55258

9812

54865

50124

8.9%

9742 9845


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2012 Top 10 Advances of Interventional Cardiology

Studies selected from the following journals

Journals 2012 # articles related to PCI

New Engl J Med 20

JAMA / (Lancet) 5 (3)

Circulation 68

J Am Coll Cardiol/JACC Intervention 72

ACCi2 meeting abstracts 112AHA meeting abstracts 45

TCT meeting abstracts 22

324


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Reasons for selection of the study

Revolutionary / significant observation

Widespread acceptance

Change in clinical practice


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1.

2.

3.

4.

5.6.

7.

8.9.

10. TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS


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TRILOGY ACS STUDY DESIGNMedically Managed UA/NSTEMI Patients

1. All patients were on aspirin and low-dose aspirin (75 years, 5mg MD or prasugrel was given.

Primary Efficacy Endpoint: CV Death, MI, Stroke

Median Time toEnrollment = 4.5 Days

Randomization Stratified by:

Age, Country, Prior Clopidogrel Treatment

(Primary analysis cohort Age < 75 years)

Medical Management Decision < 10 days

(Clopidogrel started < 72 hrs. in hospital OR

on chronic clopidogrel) 96% of total

Medical Management Decision < 72 hrs.

(No prior clopidogrel given 4% of total)

Clopidogrel1

300 mg LD

+

75 mg MD

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

Prasugrel1

30 mg LD

+

5 or 10 mg MD

Clopidogrel1

75 mg MD

Prasugrel1

5 or 10 mg MD


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TRIOLOGY Trial: Efficacy Endpoint and

TIMI Major Bleeding Through 30 Months(Overall population)

End

point

Days

20.3% PrimaryEfficacyEndpoint

TIMIMajorBleeding

0

5

10

15

20

0 180 360 540 720 900

Clopidogrel Prasugrel

HR (95% CI):1.23 (0.84, 1.81)

P = 0.29

HR (95% CI):0.96 (0.86, 1.07)

P = 0.45

18.7%

1.8 %

2.5 %

Roe et al., NEJM 2012:367:1297


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Endpoint(%)

Days

16.0% PrimaryEfficacy

2.1%1.5%

13.9% Endpoint

TIMIMajorBleeding

HR (95% Cl):1.31 (0.81, 2.11)

p=0.27

HR (95% Cl):0.91 (0.79, 1.05)

p=0.21

Prasugrel Clopidogrel

Trilogy ACS: Primary Efficacy Endpoint and TIMI

Major Bleeding Through 30 Months(Age


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Trilogy ACS Trial: Incidence of Outcomes by

Angiography Status

Angio(n=3085)

Angio(n=3085)

%

p=0.031

p=0.042

p=0.626

p=0.074

No Angio(n=4158)No Angio(n=4158)

Prasugrel Clopidogrel

p=0.954

p=0.989p=0.569

p=0.851

%

Primary MI CV TIMI

Endpoint Death Major

Bleeding

Primary MI CV TIMI

Endpoint Death Major

Bleeding


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1.

2.

3.

4.

5.6.

7.

8.9. IABP Trials: CRISP-AMI, IABP-SHOCK II



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Percutaneous LV Assist Devices

IABPPTVA:

TandemHeartIMPELLA:

Recovers 2.5


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PROTECT II Trial Design

Hemodynamic support during high-risk, non-emergent PCI, N=654Unprotected LM or last patent conduit & EF


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ONeill W et al. ACCi2 2011.


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LV Support During High Risk PCIRecent Trials Using IABP

BCIS-1

CRISP AMI

IABP-SHOCK II


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7.4% vs 4.6%, p = 0.32

Elective IABP(n=151)

No planned (n=150)

Kaplan Meier 6 month mortality

Balloon-pump Assisted Coronary

Intervention Study: BCIS-1

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


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IABP and infarct size in patients with acute anterior MI

infarction without shock: CRISP-AMI Randomized TrialInclusion Criteria Anterior STEMI

2 mm in 2 contiguous leads orat least 4 mm in the anterior leads

Planned Primary PCI within 6 hr

Anterior STEMI

Without Shock

IABP prior to PCI Standard of Care Primary PCI alone

At least 12 hours of IABP post PCI Routine Post PCI care

Cardiac MRI performed day 3-5 post PCI

Primary Endpoint: Infarct Size on CMR1. All Patients with CMR data2. Patients with Prox LAD occlusion TIMI 0/1 flow

Clinical Events 6 months

Randomize

Open Label

(n ~ 300 )

Patel et al. JAMA 2011;306:1329


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All IABP+PCI PCI Alone P

(N=337) (N=161) (N=176) Value

Primary endpoint

Infarct size (% LV), modified ITT all patients with CMR data 0.060

N 275 133 142

Mean 39.8 42.1 37.5

Median 38.8 42.8 36.2

Infarct size (%LV), modified ITT patients prox. LAD and TIMI flow 0/1 0.110

N 192 93 99Mean 44.4 46.7 42.3

Median 42.1 45.1 38.6

Patel et al. JAMA 2011;306:1329


infarction without shock: CRISP-AMI Randomized Trial


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IABP+PCI

(N=161)

PCI Alone

(N=176)

P

Value

Death (%) 1.9* 4.0* 0.26*

Stroke (%) 1.9 0.6 0.35

Major bleed per GUSTO 1 definition or transfusion (%) 3.1 1.7 0.49

Vascular complications (%) 4.3 1.1 0.09

Major limb ischemia requiring operative intervention (n) 0 0

Distal embolization (n) 0 0

Major dissection (n) 2 0

Pseudoaneurysm or AV fistula (n) 3 2

Hematoma > 5 cm (n) 3 0

30-day Clinical Events

* From KM curves and log-rank test. Patel et al. JAMA 2011;306:1329


infarction without shock: CRISP-AMI Randomized Trial


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IABP-Shock II Trial: Guidelines

IABP in AMI complicated by Cardiogenic Shock

Class IC

Class IB


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299 intended early revascularization

288 primary PCI

3 primary CABG 8 no revascularization

288 received IABP

13 did not receive IABP

10 died before IABP

3 protocol violation

301 intended early revascularization

287 primary PCI

3 primary CABG 11 no revascularization

298 with 30-day follow-up

- 1 withdrew informed consent

300 primary endpoint analysis

300 with 30-day follow

- 1 lost to follow up

298 primary endpoint analysis

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

Allocation

Revascularization

Follow-Up

Primary endpoint

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

IABP-SHOCK II Flow ChartPatient in cardiogenic shock complicating AMI

Check inclusion and exclusion criteria

Informed consent

IABP-SHOCK IIRegistry

Not suitable

Randomization

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

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


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IABP-Shock II Trial: Results Primary Study Endpoint:

30-day Mortality

Mortality(%)

Time After Randomization (Days)

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

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


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SafetyIABP (n=300) Control (n=298)

All-cause mortality 30-D; n (%) 119 (39.7) 123 (41.3)

Stroke in-hospital; n (%) 2 (0.7) 5 (1.7)Gusto bleeding: life-

threatening/severe; n (%) 10 (3.3) 13 (4.4)

Gusto bleeding: moderate; n (%) 52 (17.3) 49 (16.4)

Re-infarction in hospital; n (%) 9 (3.0) 4 (1.3)

Stent thrombosis in-hospital; n (%)

Peripheral ischemic complication

requiring intervention; n (%)

4 (1.3)

13 (4.3)

3 (1.0)

10 (3.4)

Sepsis; n (%) 47 (15.7) 61 (20.5)

P

0.15

0.71

0.77

0.51

0.69

IABP-Shock II Trial: Results

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

0.53

0.28

0.16


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1.

2.

3.

4.

5.6.

7.

8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC9. IABP Trials: CRISP-AMI, IABP-SHOCK II

10.TRIOLOGY Trial: Prasugrel vs. Clopidogrel in ACS


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Standard-Dose Clopidogrel

clopidogrel 75-mg daily X 6 months

High-Dose Clopidogrel

clopidogrel 600-mg, thenclopidogrel 150-mg daily X 6 months

Elective or Urgent PCI with DES*

VerifyNow P2Y12 Test 12-24 hours post-PCI by Accumetrics

PRU 230

RR

GRAVITAS Study Design

placebo-controlled

Primary Efficacy Endpoint: CV Death, Non-Fatal MI, Stent Thrombosis at 6 moKey Safety Endpoint: GUSTO Moderate or Severe Bleeding at 6 mo

Pharmacodynamics: Repeat VerifyNow P2Y12 at 1 and 6 months

All patients received aspirin (81-162mg daily)

*Peri-PCI clopidogrel per protocol-mandated criteria to ensure steady-state at 12-24 hrs

Price et al. JAMA 2011;305:1097.


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High-Dose Clopidogrel

Standard-Dose Clopidogrel

2.3% vs. 2.3%

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

0 30 60 90 120 150 180 210

1

2

3

4

Cumu

lativeIncidenceof

CVdeath

,non-fatalMI,orST%

No. at RiskHigh Dose Clopidogrel

Standard Dose Clopidogrel1109 1056 1029 1017 1007 998 747 541105 1057 1028 1020 1015 1005 773 53

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

Thrombosis

Observed event rates are listed; P value by log rank test. Price et al. JAMA 2011;305:1097.


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Placebo LD,then Clopidogrel 75mgdaily X 6 months

PrasugrelLoading dose 60mg, then 10mg daily

X 6 months

Elective PCI with DES without GP IIb/IIIa use

VerifyNow P2Y12 Test 2-4hrs first clopidogrel MD (75mg)

PRU 206

RR

TRIGGER PCI Trial: Study Design

Primary Efficacy Endpoint: CV Death, Non-Fatal MI at 6 moKey Safety Endpoint: Moderate or Severe Bleeding at 6 mo

Pharmacodynamics: Repeat VerifyNow P2Y12 at 3 and 6 months

All patients received aspirin (81-162mg daily)

N= 2150

Trial was halted after 432 pts enrolled because of


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TRIGGER-PCI Study

Trenk et al., JACC 2012;59:2159

Cumulative Composite Incidence of Efficacy Bleeding Events

PAI Data


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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 on-treatment platelet reactivity pre-DES

3-Adjustment of DAPT dose regimen ifhyper/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

*In the absence of high platelet reactivity (HPR), MD regimen is aspirin 75 mg + clopidogrel 75 mg.

DAPT =dual antiplatelet therapy


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ARCTIC Monitoring Arm

VerifyNow before PCI: aspirin and P2Y12 thienopyridine

Reload with 500 mg

of IV aspirin

GP IIb/IIIa + clopidogrel (re)-loading (> 600 mg) or prasugrel 60 mg and150-mg MD clopidogrel or prasugrel 10 mg+

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

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

ARU >550 > 90% inhibition< 15% inhibition/PRU > 235

ARU >550 < 15% inhibition/PRU > 235


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

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

ARCTIC Trial: Monitoring Antiplatelet Therapy for

Coronary Stenting


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ARCTIC Trial: Monitoring Antiplatelet Therapy for Coronary

StentingStudy End Points at 1 Year Follow-up*

Primary Secondary Death Death MI Stent Urgent Major or

End Point End Point recurrent ACS, thrombosis revasc Minor

stroke, TIA bleeding

p= 0.10

p= 0.77

p= 0.28

p= 0.24

p= 0.32

p= 0.51

Conventional Treatment (n=1227) Monitoring (n=1213)

p= 0.76 p= 0.08

* Patients could have more than one end point

%

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


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Routine Testing for Platelet Inhibition by

VerifyNow Assay Instrument (Accumetrics) Assessment of plateletaggregation inhibition (PI):

- Goal; Optimal response PRU230;- Make sure about compliance- PPI interaction- ? Genetic testing for2C19*2 allele polymorphism

- If on plavix, then eitherswitch to Prasugrel (30mg LD& 5-10mg MD or double

plavix dose to 150mg daily)


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GIFT Study: (Genotype Informationand Functional Testing) Study

GRAVITAS Trial

Price et al., JACC 2012;59:192


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GIFT Trial: Change in On-Treatment Reactivity

From Randomization to 30 Days by CYP2C19Genotype and Treatment Group



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GIFT Trial: Adjusted Odds Ratios for High OTR at 30 Days

and 6 Months by CYP2C19 Genotype According to MDAssignment

High on treatment platelet reactivity ispredicted by genetic makeup but any

genetic phenotype did not correlate withthe 6M MACE


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1.

2.

3.4.

5.6.

7. YELLOW Trial: Change in plaque composition




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()

, , , , , , , , ,

, ,

Presented at ACC 2012; Accepted for Publication in JACC 2013


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Chemogram

Landmark

WireDetection

BlockChemogram

Near Infrared Spectroscopy (NIRS)

NIRS provides lipid contents based onthe spectra processed by algorithm

and shown as lipid core burden index;

LCBI (range 1~1000) for each region of

interest.

Proximal


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High-Dose statin therapy will reduce lipid corecontent in severely obstructive coronary lesions inthe short term (6-8 weeks), as evaluated by Near-

infrared Spectroscopy

Hypothesis

Primary outcomeChange in coronary lipid core burden index (LCBI)after short-term high-dose statin therapy, as

determined by Near-infrared Spectroscopy (NIRS)


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Two/Three Vessel CAD

(n= 87)

After stenting the target vesselThe non-target lesion underwent FFR

FFR0.8IVUS, NIRS

RandomizedStandard Aggressive

n = 43 n = 44Continue statin the patient was taking Rosuvastatin 40 mg daily

Dual antiplatelet therapy for 1 year 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 LabData analysis for primary outcome analyzed by MSH independent Core Lab

*Optimal medical therapy for all patients


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Paired Analysis Lesion LCBI

Baseline

Follow-up

LC

BI

400

200

0

Standard Aggressive

P= 0.47 P= 0.0008

33

Absolute LCBIReduction

Case Example


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Baseline

Lesion LCBI: 259

Follow-up

Max10mm LCBI: 511

Max4mm LCBI: 802

Lesion LCBI: 177

Max10mm LCBI: 289

Max4mm LCBI: 474

Case Example

Plaque Area5.6mm2

Plaque Area5.5mm2 FFR: 0.78

FFR: 0.74


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1.

2.

3.4.

5.

6. Transradial Intervention in STEMI: RIFLE-STEACS





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Prior Meta-analysis of 23 RCTs of

Radial vs. Femoral PCI (N=7020)

Radial better Femoral better1.0

PCI Procedure Failure

Death

Death, MI or stroke

Major bleeding/Vascular Comp

1.31 (0.87-1.96)

0.74 (0.42-1.30)

0.71 (0.49-1.01)

0.27 (0.16-0.45)

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

Access Site Crossover 3.82 (2.83-5.15)

RIVAL (RadIal Vs femorAL access for


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NSTE-ACS and STEMI

(n=7021)

Radial Access

(n=3507)

Femoral Access

(n=3514)

Primary Outcome: Death, MI, stroke

or non-CABG-related Major Bleeding at 30 days

Randomization

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

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

Blinded Adjudication of Outcomes

RIVAL (RadIal Vs femorAL access for

PCI) Study Design 3831 (45%) pts weresub-study

of OASIS-7 Trial

RIVAL TRIAL


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RIVAL TRIALSecondary Outcomes at 30 days

0

2

4

6

8

%

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

3.2

p=0.90

3.2

Death, MI, Stroke

1.7

p=0.47

p=0.65

1.31.5

0.60.4

1.9

MIDeath

p=0.23

%

StrokeNon-CABG MajorBleeding

p=0.30

0.7

0.9


RIVAL Study: Subgroups: Primary Outcome


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Death, MI, Stroke or non-CABG major BleedRIVAL Study: Subgroups: Primary Outcome

0.251.00 4.00

Radial better Femoral better

Hazard Ratio (95% CI)

142.5

Lowest Tertile

Middle TertileHighest Tertile

NSTE-ACSSTEMI

Age

Gender

BMI

Radial PCI Volume by Operator

Radial PCI Volume by Centre

Diagnosis at presentation

Overall

0.786

0.356

0.637

0.536

0.021

0.025

Interactionp-value



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RIFLE STEACS Flow Chart

Romagnoli E at al. JACC 2012

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.

RIFLE STEACS T i l R lt NACE t


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RIFLE STEACS Trial: Results NACE rate

11.4 12.2

13.6

7.2 7.8

21.0

0

5

10

15

20

25

NACE MACCE Bleedings

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

%

p = 0.003

p = 0.029 p = 0.026

Mortality: 9.2% 5.2% p=0.02

Romagnoli E at al. JACC 2012

Transradial PCI in AMI: REAL Multicenter Registry


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8.8

5.7

13.9

4.8

11.4

6.9

1.7

17.7

5.8

1.2

0

5

10

15

20

All Cause

Death

MI Stroke All Cause Death/MI/Stroke

Major Bleeding/Vascular Events

Transradial Group (n = 1501) Transfermoral Group (n= 1501)

Transradial PCI in AMI: REAL Multicenter RegistryClinical Outcomes in the Propensity Score-Matched at 2Y

%

Valgimigli et al., JACC Interv 2012;5:23.

P = 0.025

P = 0.27

P = 0.45

P = 0.013

P = 0.20

2012 T 10 Ad f I t ti l C di l


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1.

2.

3.4.

5. DAPT Duration Trials: PRODIGY, RESET





(Very) Late stent thrombosis


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(Very) Late stent thrombosisDES: Factors to consider

Discontinuation ofantiplatelet therapy

Delayedendothelialization

Late incompleteapposition

Polymer hypersensitivity/inflammation

Late StentThrombosis

Optimal Duration of ADP Receptor Blockers Post DES


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Optimal Duration of ADP Receptor Blockers Post DES

Still Remain Unclear (Aspirin 81-325 mg daily for life)

Cypher StentLaunch

5/2003

AHA/ACC PCIGuidelines 2001

(TAXUS stent 6 months post PCI)(Cypher stent 3 months post PCI)

AHA/ACC/SCAIUpdated Guidelines 2005

ESC 2005/ACC 2006PCI Updated Guidelines

(12 months post PCI)

CURE, PCI-CURE 2001CREDO 2002

TAXUS StentLaunch3/2004

(1-12 months post BMS)

9-12 months

BMS Era DES Era

(FDA recommendations)

Clopido/Prasugrel/Ticagshould be

continued for 1 yror even longer if nocontraindications

If not sure about DAPT compliance or has to be interrupted in

12M then BMS (Basket late) is safer & should be preferred

AHA/ACCUpdated Guidelines 2006

Stent Thrombosis Rates (ARC Definite)


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Stent Thrombosis Rates (ARC Definite)

XIENCEV

P=0.008

1.2

CYPHER

0.2

%

SORT-OUT IV

9 Months

XIENCEV

P=0.01

1.6

CYPHER

0.5

%

LESSON I

3 Years

XIENCEV

P


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

Antiplatelet Therapy

0

1

2

3

4

5

MI, Strokeor death

%

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

0.7 0.8

1.41.6

1.8

3.2

p=0.49

p=0.05

p=0.24

N Engl J med 2010;362:1374.

0.1 0.2p=0.35

2.4

3.1

p=0.22

0.40.4

p=0.76

Death MI TIMI MajorBleeding

Definite ST TLR

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


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0

5

10

15

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

70 % second generation DES (Xience V/ Promus/ Endeavor)

Primary end point Death / MI TIMI Major Type 2, 3 or 5

Death/ MI/ Stroke Bleeding BARC bleeding

%

6M (N = 1012)

24M (N = 1001)

10.0 10.1

8.99.6

0.61.6

p= NS

p= NS

p= 0.0002

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

3.5

7.4

p= 0.041

ST1.0%0.9%

RESET Trial: Clinical Outcomes Through 1 Year


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Kim et al., JACC 2012:60:1340

4.7 4.7

0.5

1.0

0.2

0.4

3.93.7

0.2

0.30.5

1.0

0

1

2

3

4

5

Primary Death MI TVR Stent Major or minorEnd Point thrombosis bleeding

p= 0.84

p= 0.65

p= 0.39

p= 0.41

p= 0.70

p= 0.20

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

Standard Therapy (n=1058)

g

%

DAPT DURATION POST DES


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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)


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g y ( )

After DAPT Interruption

0

0.5

1

1.5

2

SubsequentLateST(ARCDef/Prob)(%)

No Interruption InterruptionAfter 30 Days

13/3500 2/1272 0/292 0/120

InterruptionAfter 180 Days

2/435 0/157

InterruptionAfter 90 Days

1/378 0/147

Overall

0.26

0

0.370.49

Standard (Low) Risk

0

0.16

0 0

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

Proposed Management of Patients Requiring


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p g q g

Temporary DAPT Cessation: MSH Protocol

Emergent need for surgery


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1.

2.

3.4. DES Comparison Trials: RESOLUTE, PLATINUM






Drug Eluting Stent System:


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Drug Eluting Stent System:

First vs. Second Generation New Stent DesignsXIENCE V

PROMUS

ENDEAVOR TAXUSEXPRESS

LIBERTE

CYPHER

Stent Material CobaltChromium

CobaltChromium

StainlessSteel

StainlessSteel

Bare StrutThickness

0.0032 0.0036 0.0052 0.0055

Bare StrutThickness

81m 91m 132m 140m

PolymerThickness

7m 6m 16m 14m

Total

Thickness

88m 97m 148m 154m

Drug Everolimus Zotarolimus Paclitaxel Sirolimus


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Endothelial Cell Recovery Between ComparatorPolymer-Based Drug-Eluting Stents


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Polymer-Based Drug-Eluting Stents

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

Scanning Electron Micrographs of 14-DayComparator DES and BMS Controls

The upper panels show corresponding radiographic images ofeach stent. The lumens are clearly patent and struts are easilydiscerned underneath a thin neointimal surface. Among DES,there is less endothelial cell surface coverage in SES and PESstents compared with ZES and EES. The panel insets arerepresentative images at higher magnification (200) fromproximal and distal regions showing bare struts, surface thrombi,inflammatory cells, and endothelial cells.

Scanning Electron Micrographs of 28-DayComparator DES and BMS Controls

The upper panels show corresponding radiographic images of eachstent. The lumens are patent and struts are less discernable under athicker neointima relative to 14-day stents. Overall endothelialcoverage is near complete in all DES although it remains poor abovestruts in PES and SES compared with ZES and EES. The panelinsets are at higher magnification (200) from the proximal anddistal regions and show persistent uncovered struts, surface thrombi,inflammatory cells, and endothelial cells.

SPIRIT IV: Ischemia-Driven TLR Through


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Ische

mia-drivenTLR(%)

2 Years

Number at risk

XIENCE V 2458 2419 2392 2350 2318 2291 2269 2246 2226

TAXUS1229 1186 1159 1140 1124 1112 1104 1093 1073

Months

6.9%

4.5%

p=0.004

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

2.4%4.6%

2.4%

p=0.0007

HR [95%CI] = 0.54 [0.38, 0.78]

2.2%

XIENCE V (n=2458)

TAXUS (n=1229)

Stone et al. JACC 2011;58:19.

Comparison of Everolimus-Eluting Vs. Paclitaxel-


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0

2

4

6

8

10

%

Paclitaxel-Eluting Stent (n=903)

Everolimus Stent (n=897)

p=0.007

p=0.58

p=0.0001

2.0

6.0

2.02.03.0

5.0

Death MI TVR MACE Stent Thrombosis

Eluting Stents in Real-life Practice: COMPARE TrialMajor Adverse Cardiac Events

p=0.002

p=0.029.0

6.0

3.0

0.7

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

Resolute All Comers Trial


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0

3

6

9

12

15

%

Zotarolimus-Eluting Stent (n=1119) Resolute DESEverolimus-Eluting Stent (n=1126) XienceV DES

p=0.57

p=0.36

Clinical Outcomes at 24 Months

p=0.52

p=0.75

p=0.073.2

1.01.9

12.912.5

9.110.0

4.0

5.55.0

Death MI TVR MACE Stent ThrombosisDefinite/Probable

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

PLATINUM Trial: 1-Year Clinical Outcomes


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Stone et al., JACC 2011;57:1700

P=0.97

P=0.85P=0.25

P=0.83

P=0.72

P=1.00

%

Overview of Bioresorbable Stents


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Company Picture Polymer/Drug Features

Igaki-Tamai

(2000)

PLLA

PLLA plus Tranilast

Zig-zag design

deployed with a

heated balloon

Biotronik

(2006)

Mg alloy Balloon expandable

design

Abbott (BVS)

(2006)

PLLA with everolimus Balloon expandable

Reva Medical

(2008)

Tyrosine poly carbonate

with iodine radio-opacity

Design has ratchet

links for deployment

BTI

(2008)

Salicylic acid blended into

polymer

Balloon expandable

Abbott Bioabsorbable Stent (BVS) ABSORBBioabsorbable Stent Technology


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bbott oabso bab e Ste t ( S) SO

Trial

At 2 yrs FU:

progressive polymer degradation normal histopathologic healing

restored vasoreactivity

late positive remodeling

Serruys et al. Lancet 200

ABSORB B Group 1 & 2


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30 days 6 months 1 Year 2 Years

Non-Hierarchical N=101 N= 101 N=101 N=100*

Cardiac Death% 0 0 0 0

Myocardial Infarction % (n) 2.0 (2) 3.0 (3) 3.0 (3) 3.0 (3)

Q-wave MI 0 0 0 0

Non Q-wave MI 2.0 (2) 3.0 (3) 3.0 (3) 3.0 (3)

Ischemia driven TLR % (n) 0 2.0 (2) 4.0 (4) 6.0 (6)

CABG 0 0 0 0

PCI 0 2.0 (2) 4.0 (4) 6.0 (6)

Hierarchical MACE % (n) 2.0 (2) 5.0 (5) 6.9 (7) 9.0 (9)*one patient missed the 2-year FUP

No scaffold thrombosis by ARC or Protocol out to 2-YearOnly 2 additional TLR events between 1 year and 2 years

Clinical Results - Intent to treat

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.

MACE: Cardiac death, MI, ischemia-driven TLRTVF: Cardiac death, MI, ischemia-driven TLR, ischemia-driven TVR

Drug Eluting Stents Comparison:RCT(Scale of 1+Bad to 4+Best)


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(Scale of 1+Bad to 4+Best)

Cypher Taxus Resolute/E Xience/Promus

Efficacy

TLR ++++ +++ + ++++

MI - - ++ ++

Death - - - -

Safety

Early stentthrombosis

- - -/+ ++

Late stent

thrombosis

- - ++ +++

Crossability/Trackability - + ++++ ++++

Market Share (%) -


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1.

2.

3. SYNTAX Trial: 5-Year follow-up4. DES Comparison Trials: RESOLUTE, PLATINUM






SYNTAX Trial


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Limited ExclusionCriteriaPrevious

interventions (PCI orCABG)Acute MI with CPK>2xConcomitant valve

surgery

De novo disease

Isolated left mainRevascularization inall 3 vascular territories

3-vessel diseaseleft main +1-vessel disease

left main +2-vessel disease

left main +3-vessel disease

Eligible PatientsSyntax Objective: To compare the MACCE rate at 12 months between patients

treated with TAXUSstents vs. patients undergoing CABG for de novo 3VDand/or LM disease. (*MACCE = major adverse cardiac and cerebrovascularevents; defined as death, stroke, MI, or repeat revascularization)

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

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


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ITT population

TAXUS (N=903)CABG (N=897)

Months Since Allocation

CumulativeEventRate(%)

Before 1 year*

7.7% vs 7.6%P=0.98

1-2 years*

2.2% vs 3.5%P=0.11

2-3 years*

2.5% vs 3.8%P=0.14

3-4 years*

2.7% vs 4.6%P=0.051

16.7%

0

25

50

20.8%

4-5 years*

3.1% vs 3.1%P=0.98

P=0.03

0 12 6024 36 48

P=0.03

SYNTAX Trial: Repeat Revascularization to 5 Years


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ITT population


P


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0000CumulativeEv

entRate(%)

Months Since AllocationITT population

Before 1 year*

12.4% vs 17.8%P=0.002

1-2 years*

5.7% vs 8.3%P=0.03

2-3 years*

4.8% vs 6.7%P=0.10

3-4 years*

4.2% vs 7.9%P=0.002

P


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Syntax score is purelyan anatomic score of the

extent of CAD (>50%) in a pt

Each lesion is assigned anumerical number and then

sum of all lesions scorefor a patient is

calculated to come upwith the final numerical

Syntax score

Pt are divided in 3 groups:

Low 32

SYNTAX Trial: MACCE vs. SYNTAX Score


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0

5

10

15

20

25

22 23-32 33

MACCEat12M

onths(%)

14.7

13.6 12.0

16.7

10.9

23.4*

SYNTAX Score

*P= 0.03 vs PCI with SYNTAX score 22P= 0.002 vs PCI with SYNTAX score 23-32

Trend for PCI: P=0.006

P< 0.001


CABG (n= 897)

TAXUS (n= 903)

SYNTAX Trial:MACCE to 5 Years by


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CABG PCIP

value

Death 10.1% 8.9% 0.64

CVA 4.0% 1.8% 0.11

MI 4.2% 7.8% 0.11

Death,

CVA orMI

14.9% 16.1% 0.81

Revasc 16.9% 23.0% 0.06

P=0.43

OverallTAXUS (N=299)CABG (N=275)SYNTAX Score Tercile Low Scores (0-22)

32.1%

28.6%

Cumulative KM Event Rate 1.5 SE; log-rank Pvalue

Months Since Allocation

CumulativeEve

ntRate(%)

0 12 24

50

0

25

4836 60

SYNTAX Trial:MACCE to 5 Years by SYNTAX


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CABG PCIP

value

Death 12.7% 13.8% 0.68

CVA 3.6% 2.0% 0.25

MI 3.6% 11.2%


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OverallTAXUS (N=290)CABG (N=315)

Score Tercile High Scores (33)

P


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RevascMethod

COR LOE

CABG I B

PCI IIaFor SIHD when low risk of PCI complications and high likelihood ofgood long-term outcome (e.g., SYNTAX score of 22, ostial or trunk left

main CAD), and a signficantly increased CABG risk (e.g., STS-predictedrisk of operative mortality 5%)

B

IIbFor SIHD when low to intermediate risk of PCI complications andintermediate to high likelihood of good long-term outcome (e.g., SYNTAXscore of 2%)

B

III: HarmFor SIHD in patients (versus performing CABG) withunfavorable anatomy for PCI and who are good candidates for CABG

B

IIaFor UA/NSTEMI if not a CABG candidate B

IIaFor STEMI when distal coronary flow is


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CABG PCI

Two-vessel CAD with proximal LAD stenosis A A

Three Vessel CAD with low CAD burden (i.e., threefocal stenosis, low SYNTAX score) A A

Three-vessel CAD with intermediate to high CAD burden (i.e., multiple

diffuse lesions, presence of CTO, or high SYNTAX score >32). A UIsolated left main stenosis A U

Left main stenosis and additional CAD with low CAD burden (i.e., one to twovessel additional involvement, low SYNTAX score 32)

A I

Patel et al., JACC 2012; 59:0000

and LM Coronary Artery disease

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

As you all know, since Jan 2010, we have incorporated Syntax score in stratifying patients for revascularization choices

(PCI CABG) f d d CAD d t ith S t33 h t hi h i l i k b i f ti ll


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(PCI or CABG) for advanced CAD and pts with Syntax score 33 who are not high-surgical risk, being preferentiallyreferred 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).

Patients with SYNTAX Score >22 but following situations and co-morbidities could be excluded from routine CT

surgery consultations:

1) Acute MI (STEMI or Non-STEMI)

2) Age >80 years old

3) Prior CVA/recent TIA

4) Severe COPD (FEV1 50

6) 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. CABGfor Examination of LM Disease)


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LM disease (1, 2 or 3 vessel disease) and aSYNTAX 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.



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1.

2. FAME II Trial: PCI vs. MMT







FAME II Trial: Flow ChartStable patients scheduled for 1, 2 or 3 vessel DES stenting


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FFR in all targets lesions

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

Randomized TrialRegistry

At least 1 stenosiswith FFR < 0.80

When all FFR >0.80

OMT

OMTPCI + OMT

Randomization 1:1

50 % randomlyassigned to FU

FAME II Trial: Cumulative Incidence of Primary

E d P i t d It C t


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Bruyne et al., NEJM 2012:367:991

End Points and Its Components

FAME II Trial Results


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FFR-GuidedPCI

(n=447)MT

(n=441)p

value

Primary Endpoint 4.3% 12.7%


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(

%)

3.1

1.6 1.6

3.62.4

1.2

19.5

11.1

8.6

0

5

10

15

20

Any Revascularization Urgent

Revascurization

Non-Urgent

Revascurizaton

PCI+MT (n=447)

Registry (n=166)

P


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Conclusions

In patients with stable coronary artery disease and functionally significant stenosis, FFR-guided 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)

Page 991


1 FREEDOM Trial CABG PCI i MV di b t


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1. FREEDOM Trial: CABG vs. PCI in MV diabetes








FREEDOM Trial: TRIAL SCREENING & ENROLLMENT

32 966 Patients were screened for eligibility


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16 withdrew post-procedure

43 were lost to follow-up

947 Randomized to CABG*18 underwent PCI/DES

26 withdrew prior to procedure3 died prior to procedure7 underwent neither PCI/DES or

CABG

953 Randomized to PCI/DES*5 underwent CABG

3 withdrew prior to procedure3 died prior to procedure3 underwent neither PCI/DES or

CABG

32,966 Patients were screened for eligibility

3,309 were eligible (10%)

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

36 withdrew post-procedure

51 were lost to follow-up

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

PCI/DES

FREEDOM Trial: PRIMARY OUTCOME DEATH / STROKE / MI


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30

20

10

0

Death/Stroke/MI%

PCI/DES

Logrank P=0.005

CABGPCI/DES

CABG

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 40

CABG N 947 814 758 613 422 221 44

FREEDOM Trial: ALL-CAUSE MORTALITY

PCI/DES


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0 1 2 3 4 5

0

10

20

30

All-Cause

Mor

tality% CABG

CABG

PCI/DES

953 897 845 685 466 243PCI/DES N

947 855 806 655 449 238CABG N

Logrank P=0.049

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

FREEDOM Trial: MYOCARDIAL INFARCTION

%PCI/DES


99/109

Years post-randomization0 1 2 3 4 5

0

10

20

30

MyocardialInfar

ction%

C S

CABG

CABG

PCI/DES

953 853 798 636 422 220PCI/DES N

947 824 772 629 432 229

Logrank P


100/109


0 1 2 3 4 5

0

10

20

30

Stroke%

PCI/DES

CABG

PCI/DES 2.4%

CABG

953 891 833 673 460 241PCI/DES N

947 844 791 640 439 230CABG N

Logrank P=0.034

5.2%

Severely DisablingScale CABG PCI/DES

NIH > 4 55% 27%

Rankin >1 70% 60%

30

,%

PCI/DES

CABG

FREEDOM Trial: REPEAT REVASCULARIZATION


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0

10

20

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

Months post-procedure

RepeatRevascularization

CABG

PCI/DES

944 887 856 818 792PCI/DES N911 858 836 825 806CABG N

Log rank P


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100

90

80

70

60

50

4030

20

10

0

0.0 1.0 2.0 3.0 4.0 5.0

SYNTAX Score 22 (N 669)

CABG

PCI/DES

5-Year Event Rates: 23.2%17.2%

FreedomfromEvent(%


100

90

80

70

60

50

4030

20

10

0

0.0 1.0 2.0 3.0 4.0 5.0

SYNTAX Score 23 32 (N 844)

CABG

PCI/DES

FreedomfromEvent(%



100

90

80

70

60

50

4030

20

10

0

0.0 1.0 2.0 3.0 4.0 5.0

SYNTAX Score 33 (N=374)

CABG

PCI/DES

Freedomf

romEvent(%)



Conclusions In patients with diabetes and advanced coronary

disease, CABG was of significant benefit as


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disease, CABG was of significant benefit ascompared to PCI. MI & all cause mortality wereindependently decreased, while stroke was

slightly increased

There was no significant interaction between the

treatment effect of CABG on the primaryendpoint according to SYNTAX score or anyother prespecified subgroup.

CABG surgery is the preferred method ofrevascularization for patients with diabetes &multi-vessel CAD.




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8. Platelet Inhibition Studies: TRIGGER PCI, ARCTIC

9. IABP Trials: CRISP-AMI, IABP-SHOCK II



R f l i f h i l


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Reasons for selection of the articles

Revolutionary / significant observation

Widespread acceptance

Change in clinical practiceIABP, PI Testing, Prasugrel in ACS:

Infraredex, Xience V:

DAPT 6M, TRI in STEMI:

FREEDOM, FAME II, Syntax Scoring:

Final result BETTER INTERVENTION/SURVIVAL

2007 (n= 4422)2008 (n= 4594)

MSH:Temporal Trends in Complications of PCIOver 5 years with


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0

0.2

0.4

0.6

0.8

%

2008 (n= 4594)

2009 (n= 5078)

2010 (n= 4799)

2011 (n= 4707)

In-hospital death Urgent CABG Q-wave/Large MI Major Complications(death, rCABG, MI, CVA)

0.06

0.0

0.21

0.270.24

0.16

0.23

0.040.0

0.080.09

0.110.09

0.08 0.08

0.490.520.53 0.51

0.58

...


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PCI Statistics 2008-10 # cases All casesNon-Emergency Emergencycases cases

1. Mount Sinai Hospital 14414 0.64** 0.41** 2.55

2. Saint Francis Hospital 9045 0.61** 0.35** 2.74

3. Columbia Presbyterians H 8750 0.87 0.59 2.36

4. Lenox Hill Hospital 8504 0.81 0.47 3.24

5. Saint Josephs Hospital 6510 0.83 0.58 2.576. North Shore Hospital 6112 0.70 0.56 1.72**

7. LIJ Medical Center 5896 0.63 0.36 2.45

8. Rochester General Hospital 5801 1.29* 0.77* 4.33

9. Stony Brook Hospital 5335 0.98 0.58 3.48

10. Beth Israel Medical Ctr 5073 0.65 0.30** 3.70

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

NYS Total 162918 0.90 0.55 3.17http://www.nyhealth.gov

Data on Top 10 Volume Centers in NY State 30-Day RAMR

PCI S i i f 20 0Non-Emergency Emergency

NYS-DOH Report of PCI 2010


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PCI Statistics for 2010 # cases All casesNon Emergency Emergencycases cases

1. Mount Sinai Hospital 4777 0.57 0.36 2.55

2. Saint Francis Hospital 2936 0.74 0.48 2.74

3. Columbia Presbyterians H 2856 0.81 0.55 2.36

4. Lenox Hill Hospital 2740 0.71 0.40 3.75

5. St Josephs Hospital 2314 0.86 0.61 2.886. LIJ Medical Center 2019 0.84 0.63 2.07

7. Stony Brook Hospital 1762 0.93 0.52 3.78

8. Beth Israel Medical Ctr 1762 0.75 0.40 3.89

9. Rochester General Hospital 1899 0.95 0.73 2.50

10. North Shore Hospital 1850 0.78 0.56 2.32

NYS Total 54035 0.84 0.51 3.09http://www.nyhealth.gov


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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.)

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