CVD Critical Pathways Group 2006 Teleconferences

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CVD Critical Pathways Group 2006 Teleconferences

• September 13, 2006
• 1200 Noon ET (900 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
MedicineHarvard Medical SchoolSenior
Investigator, TIMI Study GroupAssociate
Physician, Cardiovascular DivisionBrigham and
Womens HospitalBoston, Massachusetts
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Disclosure Statement

• 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.

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Faculty Disclosure Statement

• 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.

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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?
• Yes, the new information will not change my
  practice
• Yes, but I will also recommend longer-term
  antiplatelet therapy to reduce the risk of late
  stent thrombosis
• No, I will return to using bare-metal stents
• No, I have not been using drug-eluting stents so
  this will not change my practice

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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)

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PCI in Patients Receiving Enoxaparin or UFH
Following Fibrinolytic Therapy for STEMIPCI
ExTRACT-TIMI 25
C. Michael Gibson, Sabina A. Murphy, David A.
Morrow, Carolyn H. McCabe, Dietrich C. Gulba,
Gilles Montalescot, Servet Cetin, Oscar H.
Kracoff, Basil S. Lewis, Nathan Roguin, Elliott
M. Antman,Eugene Braunwald, for the ExTRACT-TIMI
25 Investigators
Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialresu
lts.org.
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Background Main Results ExTRACT-TIMI 25
Main Secondary Endpoint Death, non-fatal re-MI,
urgent revascularization by 30 days
Primary Endpoint Death or non-fatal re-MI by 30
days
UFH
UFH
14.5
12.0
11.7
9.9
ENOX
ENOX


RR 0.83 p 0.000003
RR 0.81 p 0.000001
Days
Days
Adapted with permission from www.clinicaltrialresu
lts.org.
N Engl J Med. 20063541477-1488.
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Anticoagulation for PCI
ONLY blinded study drug to be usedAll Pts
receive BOTH blinded Enox/Plac AND UFH/Plac
lt 8h since SC dose
gt 8 h since SC dose Additional
Enox/Plac NO 0.3 mg/kg
IV Additional UFH/Plac GP IIb/IIIa ACT 200
s ACT 200 s No GP IIb/IIIa ACT 250 s
ACT 250 s ACT TESTING ONLY
BY UNBLINDED MEDICAL PROFESSIONAL Sheath
Removal Closure Device End of PCI No
Closure Device Wait 6 hours after last sc/IV
dose After PCI STUDY MEDICATION SHOULD
NOT BE Groin Hemostasis STARTED UNLESS
CLINICALLY INDICATED
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 Characteristics PCI Cohort N
4,676
57
Age (yrs)-median
87
CrCl (ml/min)-median
82
Male ()
20
UFH within 3 h ()
37
Hypertension ()
0.7
LMWH within 7 d ()
23
Hyperlipidemia ()
92
Killip Class I ()
51
Current smoker ()
TIMI Risk Score (STEMI)
16
Diabetes ()
27
gt 3 ()
11
Prior MI ()
41
Anterior MI ()
ALL P NS for ENOX vs UFH
Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialres
ults.org.
12
PCI Cohort Primary EndpointDeath or Nonfatal MI
by 30 days
UFH
15
13.8
ENOX
10.7
10
RR 0.77 p0.001
Death or MI ()
5
0
0
5
10
15
20
25
30
Days
Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialres
ults.org.
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PCI Cohort Safety
Event ENOX UFH RR P-Value n2,238
n2,377 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 Study 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

Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialres
ults.org.
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Death or Nonfatal MI by 30 days Among PCI
Patients in Whom Study Drug Was Not Discontinued
(n1501)
UFH
20
18.9
15
ENOX
14.2
RR 0.75 p0.018
Death or MI ()
10
5
0
0
5
10
15
20
25
30
Days
Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialres
ults.org.
16
Death or Nonfatal MI by 30 days Among PCI
Patients in Whom Study Drug Was Discontinued and
Resumed For PCI (n677)
20
RR 0.41 p0.004
UFH
15
14.4
Death or MI ()
10
ENOX
5.9
5
0
0
5
10
15
20
25
30
Days
Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona,
Spain.Adapted with permission from
www.clinicaltrialresults.org.
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Conclusion

• When compared to UFH as adjunctive therapy among
  patients undergoing PCI, ENOX
• Reduced death or MI
• Reduced stroke
• No difference in bleeding

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

• 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 onset and ?
  occurrence of reMI, both of which may expand
  window of opportunity to perform PCI following
  fibrinolytic administration.

Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialres
ults.org.
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Clinical Implications

• Among STEMI pts treated with lytic, ENOX can be
  administered as the sole antithrombin therapy
  before and during PCI without the need for
  additional antithrombin inhibition.
• Periprocedural ENOX is preferable to UFH in the
  management of these patients.

Gibson M. Presented at World Congress of
Cardiology September 4, 2006 Barcelona, Spain.
Adapted with permission from www.clinicaltrialres
ults.org.
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(No Transcript)
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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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Nordman AJ, et al. Hot Line Session. Presented at
World Congress of Cardiology, September 3, 2006,
Barcelona.
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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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Cause-Specific Non-Cardiac Deathsin Patients
Treated with SES
Nordman AJ, et al. Hot Line Session. Presented at
World Congress of Cardiology, September 3, 2006,
Barcelona.
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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
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Incidence of Late Stent Thrombosis gt 6 Months
Per 1,000 pts
RR 7.1 p 0.025
RR 3.7 p 0.014
p 0.33
Bavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM
2006. In press
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Incidence of Late Stent Thrombosis gt 1 Year
Per 1,000 pts
RR 5.7 p 0.049
RR 5.0 p 0.02
p 0.22
Bavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM
2006. In press
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Median Time of Late Stent Thrombosis
Months
20
p 0.04
p 0.0003
p 0.0052
16
12
8
4
0
DES/BMS
SES/BMS
PES/BMS
Bavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM
2006. In press
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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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Lagerqvist B, et al. Hot Line Session. Presented
at World Congress of Cardiology, September 4,
2006, Barcelona, Spain.
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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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Lagerqvist B, et al. Hot Line Session. Presented
at World Congress of Cardiology, September 4,
2006, Barcelona, Spain.
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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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de Winter RJ. 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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de Winter RJ. Hot Line Session. Presented at
World Congress of Cardiology, September 4, 2006,
Barcelona, Spain.
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Featured Institution University of TexasHealth
Science Center San Antonio, Texas University of
TexasCollege of PharmacyAustin, Texas
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Polling Question 2
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.)

• 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

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Progress ChecklistImmediate Goals
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Progress ChecklistShort-term Goals/Activities
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Progress ChecklistLong-term Goals/Activities
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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 Patients Hospitalized With CVD
Faculty Gregg C. Fonarow, MD