Strive Teleconf Presentation Sept13 2006

CVD Critical Pathways Group 2006 Teleconferences

September 13, 200612:00 Noon ET (9:00 AM PT)

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

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Faculty

Christopher P. Cannon, MDAssociate Professor of Medicine

Harvard Medical SchoolSenior Investigator, TIMI Study Group

Associate Physician, Cardiovascular DivisionBrigham and Women’s Hospital

Boston, Massachusetts

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The Network for Continuing Medical Education requires

that CME 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

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Christopher P. Cannon, MD, has received grant/research support from Merck & Co., Inc., AstraZeneca Pharmaceuticals PL, and Merck/Schering Plough Partnership. He has served as a consultant on scientific/advisory boards of AstraZeneca Pharmaceuticals PL, Bristol-Myers Squibb Company, GlaxoSmithKline, Merck & Co., Inc., Merck/Schering Plough Partnership, Pfizer Inc, sanofi-aventis, and Schering-Plough Corporation. He has received honoraria for CME lectures supported by AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Merck & Co., Inc., Millennium Pharmaceuticals, Inc., Pfizer Inc, sanofi-aventis, and Schering-Plough Corporation.

The team from University of Texas Health Science Center and College of Pharmacy reports no such relationships.

Faculty Disclosure Statement

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Polling Question #1

Given the study results presented at the World Congress of Cardiology 2006, will you continue to recommend drug-eluting stents for ACS?

1) Yes, the new information will not change my practice

2) Yes, but I will also recommend longer-term antiplatelet therapy to reduce the risk of late stent thrombosis

3) No, I will return to using bare-metal stents

4) No, I have not been using drug-eluting stents so this will not change my practice

Highlights from the World Congress of Cardiology

2006

Christopher P. Cannon, MD

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Highlights From WCC 2006

PCI ExTRACT-TIMI 25: Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction (PCI in Patients Receiving Enoxaparin or UFH Following Fibrinolytic Therapy for STEMI)

Drug-eluting Stents Meta-analyses (2): Results from long-term data

FRISC II: Fast Revascularization during Instability in Coronary Artery Disease (5 Year Results)

ICTUS: Invasive versus Conservative Treatment in Unstable Coronary Syndromes (3-Year Results)

PCI in Patients Receiving Enoxaparin PCI in Patients Receiving Enoxaparin or UFH Following Fibrinolytic or UFH Following Fibrinolytic

Therapy for STEMI:Therapy for STEMI:PCI ExTRACT-TIMI 25PCI ExTRACT-TIMI 25

C. Michael Gibson, Sabina A. Murphy, David A. Morrow, C. Michael Gibson, Sabina A. Murphy, David A. Morrow, Carolyn H. McCabe, Dietrich C. Gulba, Gilles Montalescot, Servet Cetin, Carolyn H. McCabe, Dietrich C. Gulba, Gilles Montalescot, Servet Cetin,

Oscar H. Kracoff, Basil S. Lewis, Nathan Roguin, Elliott M. Antman,Oscar H. Kracoff, Basil S. Lewis, Nathan Roguin, Elliott M. Antman,Eugene Braunwald, for the ExTRACT-TIMI 25 InvestigatorsEugene Braunwald, for the ExTRACT-TIMI 25 Investigators

Adapted with permission from www.clinicaltrialresults.org.

Gibson M. Presented at World Congress of Cardiology; September 4, 2006; Barcelona, Spain.

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Background: Main Results Background: Main Results ExTRACT-TIMI 25ExTRACT-TIMI 25

Primary Endpoint:Primary Endpoint:Death or non-fatal re-MI by 30 daysDeath or non-fatal re-MI by 30 days

Primary Endpoint:Primary Endpoint:Death or non-fatal re-MI by 30 daysDeath or non-fatal re-MI by 30 days

Main Secondary Endpoint:Main Secondary Endpoint:Death, non-fatal re-MI, urgent Death, non-fatal re-MI, urgent

revascularization by 30 daysrevascularization by 30 days

Main Secondary Endpoint:Main Secondary Endpoint:Death, non-fatal re-MI, urgent Death, non-fatal re-MI, urgent

revascularization by 30 daysrevascularization by 30 days

N Engl J Med.N Engl J Med. 2006;354:1477-1488. 2006;354:1477-1488.

12.0

9.9

UFH UFH

ENOX ENOX

14.5

11.7

Days Days

%% RR = 0.83p = 0.000003

RR = 0.81p = 0.000001

Adapted with permission from www.clinicaltrialresults.org.

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Anticoagulation for PCIAnticoagulation for PCI

< 8h since SC dose < 8h since SC dose >> 8 h since SC dose 8 h since SC dose

Additional Enox/PlacAdditional Enox/Plac NO NO 0.3 mg/kg IV 0.3 mg/kg IV

Additional UFH/PlacAdditional UFH/PlacGP IIb/IIIaGP IIb/IIIa ACT 200 s* ACT 200 s* ACT 200 s* ACT 200 s*No GP IIb/IIIaNo GP IIb/IIIa ACT 250 s* ACT 250 s* ACT 250 s* ACT 250 s* * *ACT TESTING ONLY BY UNBLINDED MEDICAL PROFESSIONALACT TESTING ONLY BY UNBLINDED MEDICAL PROFESSIONAL

Sheath RemovalSheath RemovalClosure DeviceClosure Device End of PCIEnd of PCI

No Closure Device No Closure Device Wait 6 hours after last sc/IV dose Wait 6 hours after last sc/IV dose

After PCIAfter PCI STUDY MEDICATION SHOULD NOT BE STUDY MEDICATION SHOULD NOT BE + Groin Hemostasis + Groin Hemostasis STARTED UNLESS CLINICALLY INDICATED STARTED UNLESS CLINICALLY INDICATED

ONLY blinded study drug to be usedONLY blinded study drug to be usedAll Pts receive BOTH blinded Enox/Plac AND UFH/PlacAll Pts receive BOTH blinded Enox/Plac AND UFH/Plac

Gibson M. Presented at World Congress of Cardiology; September 4, 2006; Barcelona, Spain.Adapted with permission from www.clinicaltrialresults.org.

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Baseline CharacteristicsBaseline Characteristics PCI Cohort PCI Cohort N = 4,676N = 4,676

4141

1111

1616

5151

2323

3737

8282

5757

Prior MI (%)Prior MI (%)

Hypertension (%)Hypertension (%)

Hyperlipidemia (%)Hyperlipidemia (%)

Current smoker (%)Current smoker (%)

Diabetes (%)Diabetes (%)

Anterior MI (%)Anterior MI (%)

Male (%)Male (%)

Age (yrs)-medianAge (yrs)-median

ALL P = NS for ENOX vs UFHALL P = NS for ENOX vs UFH

2727

9292

0.70.7

2020

8787

> 3 (%)> 3 (%)

LMWH within 7 d (%)LMWH within 7 d (%)

Killip Class I (%)Killip Class I (%)

TIMI Risk Score (STEMI)TIMI Risk Score (STEMI)

UFH within 3 h (%)UFH within 3 h (%)

CrCl (ml/min)-medianCrCl (ml/min)-median

Gibson M. Presented at World Congress of Cardiology; September 4, 2006; Barcelona, Spain. Adapted with permission from www.clinicaltrialresults.org.

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PCI Cohort: Primary EndpointPCI Cohort: Primary EndpointDeath or Nonfatal MI by 30 daysDeath or Nonfatal MI by 30 days

ENOX

DaysDays

13.8%

0055

1010

1515

00 55 1010 1515 2020 2525 3030

De

ath

or

MI (

%)

De

ath

or

MI (

%)

UFH

10.7%

RR 0.77RR 0.77p=0.001p=0.001


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PCI Cohort: SafetyPCI Cohort: Safety

Event ENOX UFH RR P-Value n=2,238 n=2,377

TIMI Major Bleed 1.4% 1.6% 0.87 (0.55-1.39) 0.56

TIMI Minor Bleed 3.3% 2.4% 1.34 (0.95-1.88) 0.09

TIMI Major or 4.6% 4.0% 1.15 (0.88-1.51) 0.31 Minor Bleed

ICH 0.2% 0.4% 0.42 (0.13-1.35) 0.18

Stroke 0.3% 0.9% 0.30 (0.12-0.75) 0.006 Gibson M. Presented at World Congress of Cardiology; September 4, 2006; Barcelona, Spain.Adapted with permission from www.clinicaltrialresults.org.

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PCI Performed on Blinded PCI Performed on Blinded Study DrugStudy Drug

Two scenarios in which a patient underwent PCI on study drug:

1) Blinded study drug never discontinued and PCI performed on blinded study drug

2) Blinded study drug discontinued prior to PCI and then resumed at time of PCI


15

05

10

15

20

0 5 10 15 20 25 30Days

UFH

ENOX14.2%

18.9%

De

ath

or

MI (

%)

De

ath

or

MI (

%)

Death or Nonfatal MI by 30 days Among PCI Death or Nonfatal MI by 30 days Among PCI Patients in Whom Study Drug Was Patients in Whom Study Drug Was

NotNot Discontinued Discontinued (n=1501)(n=1501)

RRRR 0.750.75

p=0.018p=0.018


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Death or Nonfatal MI by 30 days Among PCI Death or Nonfatal MI by 30 days Among PCI Patients in Whom Study Drug Was Patients in Whom Study Drug Was

Discontinued and Resumed For PCI Discontinued and Resumed For PCI (n=677)(n=677)0

51

01

52

0

0 5 10 15 20 25 30Days

UFH

ENOX5.9%

14.4%

De

ath

or

MI (

%)

De

ath

or

MI (

%)

RR 0.41RR 0.41p=0.004p=0.004


ConclusionConclusion

• When compared to When compared to UFHUFH as adjunctive as adjunctive therapy among patients undergoing PCI, therapy among patients undergoing PCI, ENOX:ENOX:

• Reduced death or MIReduced death or MI

• Reduced strokeReduced stroke

• No difference in bleedingNo difference in bleeding


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• ENOX was associated with ↓ risk of death or reMI both among patients in whom antithrombin was continued as well as discontinued prior to PCI.

• ENOX associated with both delayed ENOX associated with both delayed onset and ↓ occurrence of reMI, both of onset and ↓ occurrence of reMI, both of which may expand window of which may expand window of opportunity to perform PCI following opportunity to perform PCI following fibrinolytic administration.fibrinolytic administration.

Conclusion (cont.)Conclusion (cont.)


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Clinical ImplicationsClinical Implications

• Among STEMI pts treated with lytic, Among STEMI pts treated with lytic, ENOX can be administered as the sole ENOX can be administered as the sole antithrombin therapy before and during antithrombin therapy before and during PCI without the need for additional PCI without the need for additional antithrombin inhibition.antithrombin inhibition.

• Periprocedural ENOX is preferable to Periprocedural ENOX is preferable to UFH in the management of these patients.UFH in the management of these patients.


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Nordman AJ, et al. Hot Line Session. Presented at World Congress of Cardiology, September 3, 2006, Barcelona.

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Trial F/U (y) N Cause of Death

RAVEL 4 10 4x cancer (lung, prostate, pancreas, GI); 3x stroke (2x hemorrhagic, 1x ischemic); 2x pneumonia; 1x PE

SIRIUS 4 15 4x cancer (2x renal, 1x colon, 1x unspecified); 4x respiratory failure; 2x stroke (1x hemorrhagic, 1x ischemic); 2x sepsis; 1x lymphoma; 1x car accident; 1x seizure disorder (Alzheimer’s disease)

C-SIRIUS 3 1 1x cancer (lung)

E-SIRIUS 3 2 1x cancer (lung); 1x sepsis

SES-SMART

1 1 1x pancreatic cancer

DIABETES 1 3 1x septic shock; 1x stroke; 1x pulmonary embolism (PE)

BASKET 1 3 3x cancer (2x colon cancer, 1x rectum cancer)

Cause-Specific Non-Cardiac Deathsin Patients Treated with SES


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Nordman AJ, et al. Hot Line Session. Presented at World Congress of Cardiology, September 3, 2006, Barcelona, Spain.

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Late Stent Thrombosis in Drug-eluting Stents (DES) vs

Bare Metal Stents (BMS)

Slides Courtesy of Deepak Bhatt, MD

Incidence of Late Stent Thrombosis: > 6 Months

RR = 7.1

p = 0.025RR = 3.7

p = 0.014p = 0.33

Per 1,000 pts

0

1

2

3

4

5

6

7

DES/BMS SES/BMS PES/BMSBavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM 2006. In press

Incidence of Late Stent Thrombosis: > 1 Year

RR = 5.7

p = 0.049RR = 5.0

p = 0.02

p = 0.22

Per 1,000 pts

0

1

2

3

4

5

6

7

DES/BMS SES/BMS PES/BMSBavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM 2006. In press

Median Time of Late Stent Thrombosis

p = 0.04p = 0.0003 p = 0.0052

Months

Bavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM 2006. In press

0

4

8

12

16

20

DES/BMS SES/BMS PES/BMS

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Lagerqvist B, et al. Hot Line Session. Presented at World Congress of Cardiology, September 4, 2006, Barcelona, Spain.

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de Winter RJ. Hot Line Session. Presented at World Congress of Cardiology, September 4, 2006, Barcelona, Spain.

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Featured InstitutionUniversity of Texas

Health Science CenterSan Antonio, Texas

University of TexasCollege of Pharmacy

Austin, Texas

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Polling Question #2

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.)

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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

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Progress Checklist:Short-term Goals/Activities

Finalize critical pathways

Launch critical pathways

Circulate memo

Grand rounds/conference: Cardiology/IM

Grand rounds/conference: Emergency Dept.

Grand rounds/conference: Nursing

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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

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Question-and-Answer Session

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Concluding RemarksChristopher P. Cannon, MD

Next program:Wednesday, October 11, 2006 – 3PM ET (12 Noon PT)

Topic:Diabetes and Metabolic Syndrome in PatientsHospitalized With CVD

Faculty:Gregg C. Fonarow, MD

Strive Teleconf Presentation Sept13 2006

Health & Medicine

Transcript of Strive Teleconf Presentation Sept13 2006