tct 2007 update

ACS Critical Pathways 2007 Teleconferences

This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership.

This activity is co-provided by the Network for Continuing Medical Educationand EduPro Resources LLC.

October 31, 2007

STRIVETM

22

Faculty

Gregg C. Fonarow, MDEliot Corday Professor of Medicine

and Cardiovascular Science

Director, Ahmanson-UCLA Cardiomyopathy Center

UCLA Division of Cardiology

UCLA Medical Center

Los Angeles, California

STRIVETM

33

The Network for Continuing Medical Education and

EduPro Resources LLC require that CME/CNE faculty

disclose, during the planning of an activity, the existence

of any personal financial or other relationships they or

their spouses/partners have with the commercial

supporter of the activity or with the manufacturer of any

commercial product or service discussed in the activity.

Disclosure Statement

STRIVETM

44

Faculty Disclosure Statement

Gregg C. Fonarow, MD, has served as a consultant to and has received research support and honoraria from Bristol-Myers Squibb Company, GlaxoSmithKline, Merck & Co., Inc., Pfizer Inc, and sanofi-aventis.

Deborah Murphy reports no such relationships.

The staff of NCME reports no such relationships.

STRIVETM

5

Report From Transcatheter Cardiovascular Therapeutics

(TCT) 2007

Gregg C. Fonarow, MD

STRIVETM

6

Polling Question #1Where do you currently stand on using DES?

1) In light of SCAAR and other recent data, my use of DES is increasing since earlier in 2007

2) In light of the GRACE Registry and other recent data, my use of DES is decreasing since earlier in 2007

3) My practice has not changed since earlier in 2007 with regard to DES

STRIVETM

7

Highlights From TCT 2007● ARMYDA-4: 600 mg clopidogrel loading dose prior to PCI in patients

on chronic clopidogrel therapy

● ARMYDA-5: antiplatelet therapy for reduction of myocardial damage during angioplasty

● HORIZONS AMI: bivalirudin vs heparin + GP IIb/IIIa inhibitors during primary angioplasty in AMI

● SPIRIT III: 1-year follow-up stent data

● Endeavor IV: 9- and 12-months results, Endeavor vs TAXUS stents

● EVENT Registry: Implications of changing stent practice from 2004 to 2006

● SCAAR: Swedish Coronary Angiography and Angioplasty Registry

● NY State Database and STENT Registry: Comparison of DES vs BMS

STRIVETM

8

Per

cent

age 7

8

P=.96

Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

ARMYDA-4: Composite Primary End Point of 30-day Death, MI, TVR

0

3

6

9

12

Placebo

600 mg clopidogrel reload

STRIVETM

9


78

Per

cent

age


Placebo

ARMYDA-4: Individual Events at 30 Days

0

2

4

6

8

10

Death MI TVR

STRIVETM

10


ARMYDA-4: Bleeding Rates


Placebo4 4

0 0

Per

cent

age

0

2

4

6

Major bleeding Minor bleeding

STRIVETM

11

ARMYDA-5: Study Design

Patients scheduled for angiography randomized to:

– 600 mg clopidogrel loading dose (n=174) 4 to 8 hours prior to angiography or

– Loading with clopidogrel in the cath lab once the coronary anatomy was defined and PCI was definite (n=176)

– Not included: 35 patients who underwent CABG and 53 patients treated with medical therapy

Primary end point: death, MI, or TVR at 30 days

44% of patients had NSTEMI; 36% had a prior MI

Di Sciascio G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

STRIVETM

12

ARMYDA-5: Results

NS5%4%Minor bleeding

.04

.005

272 PRUs

245 PRUs

241 PRUs

186 PRUs

Platelet reactivity at PCI

At 2 hours:

.5611%8%Death, MI, or TVR at 30 days

P ValueCath-lab treatment

Pretreatment

PRUs = platelet reactivity units.

Di Sciascio G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

STRIVETM

13

HORIZONS AMI: 2 Primary End Points at 30 DaysHORIZONS AMI: 2 Primary End Points at 30 Days

1) Net Adverse Clinical Events

2) Major Bleeding (non-CABG)

• Intracranial bleeding

• Intraocular bleeding

• Retroperitoneal bleeding

• Access site bleed requiringintervention/surgery

• Hematoma ≥5 cm

• Hgb ⇓ ≥3 g/dL with an overt source

• Hgb ⇓ ≥4 g/dL w/o overt source

• Reoperation for bleeding

• Blood product transfusion

andand

Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

STRIVETM

14

HORIZONS AMI: 2 Primary End Points at HORIZONS AMI: 2 Primary End Points at 30 Days (cont)30 Days (cont)

==

or

• All-cause death• Reinfarction

• Ischemic TVR• Stroke

Major adversecardiovascular events(major secondary end point)


1) Net Adverse Clinical Events

2) Major Bleeding (non-CABG)

STRIVETM

15

HORIZONS AMI: Study DrugsHORIZONS AMI: Study Drugs

UFH + GP IIb/IIIa(N=1802)

Bivalirudin(N=1800)

UFH prerandomization 65.6% 65.6%

Antithrombin in CCL

- UFH 98.9% 4.1%

- Bivalirudin 0.4% 96.9%

- Peak ACT 264 [228, 320] 357 [300, 402]

GP IIb/IIIa in CCL 94.5%a 7.2%a

- Bail-out per protocolb - 4.4%

- Abciximab 49.9% 4.0%

- Eptifibatide 44.4% 3.1%

- Tirofiban 0.2% 0.1%

a97.7% and 7.5% during PCI; bFor giant thrombus or refractory no reflow after PCI. CCL = cardiac catheterization laboratory.


STRIVETM

16

Primary Outcome Measures (ITT)

aNot related to CABG; bMACE = All-cause death, reinfarction, ischemic TVR or stroke.


Diff = 0.0% [-1.6, 1.5] RR = 0.99 [0.76, 1.30]

Psup = 1.00

Diff = -3.3% [-5.0, -1.6] RR = 0.60 [0.46, 0.77]

PNI ≤ .0001

Psup ≤ .0001

Diff = -2.9% [-4.9, -0.8]RR = 0.76 [0.63, 0.92]

PNI ≤ .0001

Psup = .006

1° end point 1° end point0

5

10

20

15

12.1

9.2 8.3

4.9 5.5 5.4

Net adverse clinical events

Major bleedinga MACEb

30-d

ay e

vent

rat

es (

%)

Bivalirudin monotherapy (N=1800)Heparin + GP IIb/IIIa inhibitor (N=1802)

STRIVETM

17

30-day Net Adverse Clinical Events

Number at risk

Bivalirudin 1800 1660 1633 16261620 1607 1544

Heparin + GP IIb/IIIa 1802 1635 1591 15781569 1552 1482

Pri

ma

ry E

nd

Po

int

Ne

t adv

ers

e cl

inic

al e

ven

ts (

%)

Time in Days

12.2%

9.3%

HR [95%CI] = 0.75 [0.62, 0.92] P=.006

Heparin + GP IIb/IIIa inhibitor (n=1802)Bivalirudin monotherapy (n=1800)


STRIVETM

18

30-day Major Bleeding (non-CABG)

Number at risk

Bivalirudin 1800 1697 1675 16681664 1653 1590

Heparin + GP IIb/IIIa 1802 1651 1617 16061598 1581 1511

Pri

ma

ry E

nd

Po

int

Ma

jor

ble

edi

ng (

%)

Time in Days

8.4%

5.0%

HR [95%CI] = 0.59 [0.45, 0.76]P<.0001

Heparin + GP IIb/IIIa inhibitor (n=1802)

Bivalirudin monotherapy (n=1800)


STRIVETM

19

30-day Bleeding End Points30-day Bleeding End Points


Bivalirudin(N=1800)

P Value

Protocol Major, non-CABGa 8.3% 4.9% <.0001

Protocol Major, All 10.8% 6.8% <.0001

Protocol Minor 15.4% 8.6% <.0001

Blood transfusion 3.5% 2.1% .01

TIMI Major 5.0% 3.1% .003

TIMI Minor 4.6% 2.8% .008

TIMI Major or Minor 9.6% 5.9% <.0001

GUSTO LTb or Severe 0.6% 0.4% .65

GUSTO Moderate 5.0% 3.1% .003

GUSTO LT or Sev or Mod 5.6% 3.5% .003

aPrimary end point; blife threatening.


STRIVETM

20

30-day MACE Components30-day MACE Componentsaa


Bivalirudin(N=1800)

P Value

Death 3.1% 2.1% .058

- Cardiac 2.9% 1.8% .035

- Noncardiac 0.2% 0.3% .75

Reinfarction 1.8% 1.8% .90

- Q wave 1.2% 1.4% .66

- Non–Q wave 0.7% 0.4% .50

Ischemic TVR 1.9% 2.6% .18

- Ischemic TLR 1.8% 2.5% .14

- Ischemic remote TVR 0.3% 0.3% 1.0

Stroke 0.6% 0.7% .69

aCEC adjudicated.


STRIVETM

21

SPIRIT III: MACE Through 365 Days

MACE = cardiac death, MI, or ischemia-driven TLR.


0

3

6

12

9

MA

CE

(%

)

0 90 180 270 365Days

9.9%

5.8%

TAXUS XIENCE

HR = 0.57 [0.36 – 0.90]Plogrank = .01

Number at risk

XIENCE 669 651 642 626 614

TAXUS 332 312 309 292 287

STRIVETM

22

Leon MB, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

P for Noninferiority <.001∆ = 3.8%

6.6% 7.2%

Endeavor(n=50/758)

Taxus(n=54/759)

TV

F R

ate

Target Vessel Failure

Endeavor IV: Primary End PointResult at 9 Months

STRIVETM

23

aDay 83, 145, 171.

Leon MB, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

.2679.4 (707.7 (58)TVF – % (#)

1.0006.6 (49)6.5 (49)MACE – % (#)

.7536.7 (50)6.3 (47)TVR – % (#)

.0854.2 (31)2.5 (19)TVR (non-TL) – % (#)

.2283.2 (24)4.5 (34)TLR – % (#)

.25000.4a (3) 31-360 days

.6250.1 (1)0.4 (3) 0-30 days

.1240.1 (1)0.8 (6)Stent Thrombosis (all) – % (#)

.2603.1 (23)2.1 (16)Death (cardiac) + MI (all) – % (#)

.1312.4 (18)1.3 (10) Non–Q wave

1.0000.1 (1)0.3 (2) Q Wave

.2082.6 (19)1.6 (12)MI (all) – % (#)

1.0000.5 (4)0.5 (4) Cardiac

1.0001.1 (8)1.1 (8)Death (all) – % (#)

P ValueTaxusn=741

Endeavorn=749

Endeavor IV: Clinical Eventsat 12 Months

STRIVETM

24

EVENT Registry: Bleeding Complications

Kleiman N, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

0.6

0.0%

2.0%

4.0%

6.0%

TIMI Major

WAVE 2

WAVE 1

WAVE 3

0.2 0.2

1.0 0.80.5

3.5

2.0 1.8

5.2

4.1

3.4

TIMI Minor Transfusion Any bleed ortransfusion

Not mutually exclusive

STRIVETM

25

EVENT Registry: Adjudicated Stent Thrombosis From Procedure to 1 Year Follow-up

Kleiman N, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

2.2%

0%

WAVE 2

WAVE 1

WAVE 3

P=.046

P=.027

(Logistic regression)

In Hospital 6 Months 12 Months

Wave 2 is ARC Probable; Wave 3 is ARC Definite or Probable

Wave 1 to Wave 3

1.1

0.80.9

1.9

1.01.2

(Log rank)

0.40.2

0.1

STRIVETM

26

Carlsson J, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

SCAAR: Adjusted Death/MI Total Cohort

BMS 10049 9529 9343 8112 6742 5265 3486 1892 5DES 6523 6222 6069 4428 2947 1868 908 322 0

BMS 9434 8424 8223 6896 5431 4012 2433 1285 2DES 6165 5673 5512 3792 2508 1525 780 287 0

0.25

0.20

0.15

0.10

0.05

0.000 1 2 3 4

Cum

ulat

ive

risk

of d

eath

or

MI

RR: 1.03 (0.93, 1.15)

BMSDES

On label useN=17,664

Time (years)

0.25

0.20

0.15

0.10

0.05

0.000 1 2 3 4

Cum

ulat

ive

risk

of d

eath

or

MI

RR: 0.96 (0.88, 1.06)

BMSDES

Off label useN=16,866

Time (years)

STRIVETM

27

Carlsson J, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

SCAAR: Restenosis atClinically Driven Re-angiography

BMS 3987 3794 3698 3079 2188 1140 50 0 0DES 3235 3142 3080 2354 1389 630 21 0 0

BMS 3586 3291 3202 2649 1812 909 24 0 0DES 2158 2034 1966 1407 846 339 11 0 0

0.10

0.08

0.06

0.04

0.02

0.000 1 2 3 4

Cum

ulat

ive

risk

of d

eath

or

MI

RR: 0.39 (0.3, 0.51)

BMSDES

On label useN=12,186

Time (years)

0.10

0.08

0.06

0.04

0.02

0.000 1 2 3 4

Cum

ulat

ive

risk

of d

eath

or

MI

RR: 0.66 (0.5, 0.88)

BMSDES

Off label useN=9,155

Time (years)

RRR 60%

ARR 4%

RRR 40%

ARR 2.5%

STRIVETM

28

NY State Database and STENT Registry

Brodie BR, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

2.98 (P<.001)2.23 (P<.001)1.171.17Adjusted HR

Second analysis of significant predictors of mortality (n=4,983)

2.301.851.191.19Adjusted HR forBMS/DES

2.171.771.251.26Unadjusted HRfor BMS/DES

9.4%6.1%7.8%4.8%DES (n=6,384)

16.6%13.5%9.2%5.6%BMS (n=7,834)

Rate of subsequent TVR

Rate of subsequent TLR

MI or deathMortality2-year data

Clinical Outcomes of DES vs BMS in the New York Database

STRIVETM

29

NY State Database and STENT Registry

Brodie BR, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

35.4%2%Year 1-2

19%9%30 days to 1 year

45.6%57.7%Timing of stent thrombosis<30 days

16.1%24.7%MACE

9.1%16%Death or MI

8.8%11.9%TVR

4.1%6.7%MI

5.7%11%Death

DES (n=5,996)BMS (n=1,359)2-year data

Clinical Outcomes of DES vs BMS in the STENT Registry

STRIVETM

30

Featured Institution

Paoli Hospital

Paoli, Pennsylvania

STRIVETM

3131

Polling Question

1) We are currently on the same item

2) We have since moved to the next checkbox on the checklist

3) We have progressed by more than one item on the checklist

4) ACS pathways are up-to-date and regularly followed

If you participated in a previous teleconference, how much progress have you made since then?

(Please refer to the checklists on the next 3 slides.)

STRIVETM

3232

Progress Checklist:Immediate Goals

Assemble team and set up meeting of working group

Develop draft pathways

Circulate pathways to all cardiology, ED, and CV nursing staff for comments

Circulate discharge plan and other tools to all cardiology, ED, and CV nursing staff for comments

STRIVETM

3333

Progress Checklist:Short-term Goals/Activities

Finalize critical pathways

Launch critical pathways

Circulate memo

Grand rounds/conference: Cardiology/IM

Grand rounds/conference: Emergency Department

Grand rounds/conference: Nursing

STRIVETM

3434

Progress Checklist:Long-term Goals/Activities

Monitor data: which registry?

NRMI

AHA Get With The Guidelines

ACC National Cardiovascular Data Registry

CRUSADE

GRACE

REACH

Other

STRIVETM

3535

Question-and-Answer Session

STRIVETM

3636

Concluding RemarksGregg C. Fonarow, MD

Next Program

Christopher P. Cannon, MDWednesday, November 14, 2007

12:00 Noon Eastern Time (9:00 AM Pacific Time)

Report From the American Heart Association (AHA) Scientific Sessions 2007

tct 2007 update

Health & Medicine

clopidogrel reloadpatti

stent registry

medical education

teleconferencesthis

use of des

primary angioplasty

grace registry

edupro resources llc