CVD Critical Pathways Group 2005 Teleconferences

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CVD Critical Pathways Group 2005 Teleconferences
November 9, 2005
This activity is supported by an educational
grant from the Bristol-Myers Squibb/Sanofi
Pharmaceuticals Partnership.
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Faculty

• Christopher P. Cannon, MD
• Associate Professor of Medicine
• Harvard Medical School
• Senior Investigator, TIMI Study Group
• Associate Physician, Cardiovascular Division
• Brigham and Womens Hospital
• Boston, 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 served as a
  consultant to AstraZeneca Pharmaceuticals LP,
  Bristol-Myers Squibb Company, GlaxoSmithKline,
  Guilford Pharmaceuticals, Merck/Schering-Plough
  Pharmaceuticals, Pfizer Inc., sanofi-aventis,
  Schering-Plough Corporation, and Vertex
  Pharmaceuticals Inc. He has also received
  research support from AstraZeneca Pharmaceuticals
  LP, Bristol-Myers Squibb Company, Merck Co.,
  Inc., and sanofi-aventis.
• William Jaquis, MD, representing the Sinai
  Hospital of Baltimore, Maryland, has served as a
  consultant to sanofi-aventis.

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Acute Management of Myocardial Infarction
Highlights From TCT 2005
Christopher P. Cannon, MD
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Polling Question 1

• Did you attend the 2005 Transcatheter
  Cardiovascular Therapeutics (TCT) Meeting?
• Yes, I attended the entire duration of the
  conference
• Yes, I attended part of the conference
• No, I did not attend

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Highlights From TCT 2005

• Senior Primary Angioplasty in Myocardial
  Infarction(Senior PAMI)
• LE MANS A Prospective, Randomized Trial of Stent
  Implantation vs Bypass Graft Surgery in Patients
  With Left Main Coronary Artery Disease
• Antiplatelet Therapy and PCI
• Assessment of the Best Loading Dose of
  Clopidogrel to Blunt Platelet Activation,
  Inflammation and Ongoing Necrosis (ALBION)
• Intracoronary Stenting and Antithrombotic
  Regimen Choose Between 3 High Oral Doses for
  Immediate Clopidogrel Effect (ISAR-CHOICE) Trial
• Antiplatelet Agents in Development

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Senior PAMI

• The Senior PAMI (Senior Primary Angioplasty in
  Myocardial Infarction) study compared
  thrombolytic therapy with primary PCI in the
  elderly
• 500 elderly patients enrolled
• Average age of patients was 78 years
• 41 women, 92 white, 23 diabetic
• Primary end point 30-day death or disabling
  stroke

Grines C. TCT 2005 October 16-21, 2005
Washington, DC.
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Senior PAMI 30-day Events
Primary end point
Grines C. TCT 2005 October 16-21, 2005
Washington, DC.
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Senior PAMI 30-day Events in Patients Aged 70
to 80 Years
Grines C. TCT 2005 October 16-21, 2005
Washington, DC.
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LE MANS

• LE MANS is a randomized, controlled study to
  compare unprotected left main stenting with CABG
  for left main disease
• 52 patients randomized to PCI 53 patients
  randomized to CABG
• Primary end point Assess LVEF, functional
  capacity, and angina status after 12 months
• Secondary end points Assess major adverse
  cardiac events (MACEs) hospital length of stay
  survival and any major adverse events (MAEs),
  defined as any MACE, procedure-related infection,
  bleeding, or renal or respiratory insufficiency

Buszman P. TCT 2005 October 16-21, 2005
Washington, DC.
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LE MANS

• Change in LVEF at 12 months was significantly
  different between the 2 groups, with PCI patients
  experiencing a significant increase in LVEF (from
  approximately 55 to 60)
• LVEF in CABG patients remained unchanged
• Angina status and treadmill stress test at
  follow-up were similar between the 2 groups

Buszman P. TCT 2005 October 16-21, 2005
Washington, DC.
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LE MANS Outcomes
NSnot significant
Buszman P. TCT 2005 October 16-21, 2005
Washington, DC.
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ALBION

• The ALBION Study (Assessment of the Best Loading
  Dose of Clopidogrel to Blunt Platelet Activation,
  Inflammation, and Ongoing Necrosis) was a
  randomized, open-label study comparing 3 loading
  doses of clopidogrel (300 mg, 600 mg, and 900 mg)
• End points Platelet aggregation and activation
  in response to ADP 5 and 20 µmol/L

Montalescot G. TCT 2005 October 16-21, 2005
Washington, DC.
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ALBION Study Design
Randomized, multicenter, open-label trial with
blind centralized laboratory assessment in
patients aged 18-85 years with NSTE-ACS (onset
lt48 h)
Clopidogrel 300-mg LD, then 75 mg qd
D2
n 5
LD
LD
LMWH and ASA
Clopidogrel 600-mg LD, then 75 mg qd
Clinical follow-up at 30 days
D2
n 34
R
R
Clopidogrel 900-mg LD, then 75 mg qd
D2
n 34
Sampling time
Hours post-LD
-
0
2
3
4
5
6
24
1
.5
ASA250500 mg on admission, then 100 mg/d plus
other standard care
Montalescot G. TCT 2005 October 16-21, 2005
Washington, DC.
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ALBION Inhibition ofPlatelet Aggregation ()
5 µmol/L ADP
20 µmol/L ADP
40 35 30 25 20 15 10 5 0
45 40 35 30 25 20 15 10 5 0
Inhibition
Inhibition
Shortened time to reach the highest level
of inhibition of the 300-mg LD
P lt .05 vs 300-mg LD
P lt .05 vs 300-mg LD
1 2 3 4 5 6
1 2 3 4 5 6
Time (h)
Time (h)
Montalescot G. TCT 2005 October 16-21, 2005
Washington, DC.
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ALBION Platelet Activation VASP at 6 Hours
A) MFI (PGE 1 ADP)
B) VASP index
P lt .05
P lt .05
30
25
20
15
10
5
0
300 mg
600 mg
900 mg
VASPvasodilator-stimulated phosphoprotein
Montalescot G. TCT 2005 October 16-21, 2005
Washington, DC.
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ALBION Patients With Increasing Troponin I at
Day 2
P NS
50.0
42.9
34.6
300-mg LD
600-mg LD
900-mg LD
Montalescot G. TCT 2005 October 16-21, 2005
Washington, DC.
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ISAR-CHOICE

• ISAR-CHOICE (Intracoronary Stenting and
  Antithrombotic Regimen Choose Between 3 High
  Oral Doses for Immediate Clopidogrel Effect)
  included 60 patients with suspected or documented
  CAD admitted to hospital for coronary angiography
• Patients received 1 of 3 clopidogrel doses (300,
  600, or 900 mg)
• Suppression of platelet function in each group
  was measured
• Findings indicate that clopidogrel at single
  doses gt600 mg is not associated with
  significantly enhanced suppression of platelet
  function due to limited clopidogrel absorption

von Beckerath N, et al. Circulation.
20051122946-2950.
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ISAR-CHOICE Maximal ADP-Induced Platelet
Aggregation 4 Hours After 300-, 600-, and 900-mg
Clopidogrel Loading Dose
B
A
P .001
P .001
120 100 80 60 40 20 0
120 100 80 60 40 20 0
ADP (20 µmol/L)-Induced Aggregation ()
ADP (5 µmol/L)-Induced Aggregation ()
P .01
P .59
P .01
P .59
300 mg
600 mg
900 mg
300 mg
600 mg
900 mg
n 20
n 20
n 20
n 20
n 20
n 20
Platelets were stimulated with a final
concentration of 5 µmol/L (A) and 20 µmol/L (B)
ADP. Circles represent single measurements bars
denote mean SD.
Adapted with permission from von Beckerath N, et
al. Circulation. 20051122946-2950.
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Antiplatelet Agents in Development

• Prasugrel (CS-747, LY640315) is a thienopyridine
  and an irreversible receptor blocker
• Preliminary data reported at TCT suggest that
  prasugrel exhibits less interpatient variability
  in responsiveness than clopidogrel
• TRITON-TIMI 38 (phase 3 trial) will study whether
  this lower variability will translate into
  improved outcome
• TRITON-TIMI 38 is expected to be completed in
  2007

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Antiplatelet Agents in Development

• AZD6140 The first oral, reversible, ADP-receptor
  antagonist
• A nonthienopyridine, in the chemical class CPTP
  (cyclopentyl triazolopyrimidine)
• Direct acting via the P2Y12 receptor
• DISPERSE-2 (phase 2 trial) to be presented at AHA
• Enrollment window Within 48 hours of non-ST
  elevation ACS
• Sample size 990 patients
• Compares 2 AZD6140 doses with clopidogrel, with
  low-dose aspirin background in all groups
• Primary end point Major/minor bleeding

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Featured Institution Sinai Hospital Baltimore,
Maryland
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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.)

• We are currently on the same item
• We have since moved to the next checkbox on the
  checklist
• We have progressed by more than one item on the
  checklist
• 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,
MDNext Program Update on the 2005 AHA
Scientific SessionsGregg C. Fonarow,
MDWednesday, December 7, 2005300 PM Eastern
Time (12 Noon Pacific Time)