HOT LINE PRESENTATION

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Warfarin Antiplatelet Vascular Evaluation- 2161
PAD PatientsDr. Sonia Anand Associate
Professor of MedicineMcMaster University

• HOT LINE PRESENTATION
• World Congress of Cardiology 2006
• Barcelona, Spain September 5, 2006

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Rationale

• Atherosclerosis is a systemic disease
• PAD patients suffer the highest rates of CV
  death, MI, and ischemic stroke
• Antiplatelet therapy reduces CV events in broad
  spectrum of patients with vascular disease (CAD,
  CBVD, PAD)
• Role of Oral anticoagulants (OAC) together with
  antiplatelets in CAD appears promising

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Primary Objectives

• To determine if moderate intensity OAC (INR 2-3),
  in combination with antiplatelet therapy, is
  superior to antiplatelet therapy alone in
  preventing
• cardiovascular death, MI, or stroke, and
• cardiovascular death, MI, stroke, or severe
  ischemia of the coronary or peripheral arterial
  circulation

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Study Design

• Central Randomization, Open trial, Blinded
  adjudication, 80 Centres, 7 Countries

PAD Patients
AP only (1,081 patients)
AP only
Rand
Run-In
Follow-up - q 3 mo. x 30-42 mo.
2-4 weeks AP OAC (INR 1.8-3.5)
AP OAC
AP OAC (1,080 patients)
6 mo.
9 mo.
3 mo.
Day 35
42 mo.or Final Visit
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Key Inclusion/Exclusion Criteria
Inclusion

• Men and women, 35-85 years plus gt1 of
• Intermittent claudication with objective evidence
  of PAD (e.g. ABI lt0.9)
• Previous vascular reconstruction (including
  amputation) or angioplasty of a peripheral artery
  
• Significant carotid artery disease
• Prior Vascular disease and ABI lt 0.9

Exclusion

• - Active bleeding or high-risk for bleeding
• Clear indication for long-term OAC use
• Clear indication for long-term (gt 3 months)
  daily NSAIDs
• Recent Stroke lt 6 months

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Key Outcomes
Efficacy

• Co-Primary 1 CV death, MI, or stroke
• Co-Primary 2 CV death, MI, stroke, or severe
  ischemia of the coronary or peripheral arterial
  circulation
• Life-threatening bleeding Fatal or
  intra-cranial, or requiring surgical
  intervention, or transfusion of at least 4 units
  of blood products
• Moderate bleeding lt 3 units of blood products

Safety
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Flow of Patients
Mean INR 2.2
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Baseline Characteristics
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Primary Outcomes
Note P1 composite of CV death, MI, stroke P2
CV death, MI, stroke, SI of limb or coronaries
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Figure 2a
Co-Primary 1 CV Death, MI, Stroke
OACAP AP
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Figure 2b
Co-Primary 2 CV Death, MI, Stroke, Severe
Ischemia
OACAP AP
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Safety Outcomes
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Life-Threatening Bleeding
OACAP AP
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Life-Threatening or Moderate Bleeding
Life-Threatening or Moderate Bleeding
OACAP AP
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Summary

• 1) Oral anticoagulants (targeting an INR range
  of 2 to 3) added to Antiplatelet therapy do not
  lower the rate of cardiovascular events, and
  increase life-threatening bleeding compared to
  Antiplatelet therapy alone in patients peripheral
  arterial disease.
• 2) Other antithrombins with a better safety
  profile or dual antiplatelet agents should be
  evaluated in this population

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Study Organization
Australia Eikelboom, 1 centre, 16 patients
Canada Anand, 26 centres, 880 patients China
Liu, 18 centres, 347 patients Hungary Keltai, 8
centres, 85 patients Netherlands van Urk, 1
centre, 18 patients Poland Budaj, 15 centres,
566 patients Ukraine Parkhomenko, 11 centres,
249 patients. DSMB chair Dagenais Adjudication
chair Sussex. Project office Anand, Yusuf,
Chin, Joldersma, Xie, Antaya, Sloane, Nowacki,
Parkinson