LongTerm Management of Patients at Risk of Atherothrombosis Section 1 Pathogenesis of Atherothrombos

1
Long-Term Management of Patients at Risk of
Atherothrombosis

Section 1
Pathogenesis of
Atherothrombosis Long-Term Outcome in

Patients at Risk
2
What is Atherothrombosis?

• Atherothrombosis is characterized by a sudden
  (unpredictable) atherosclerotic plaque disruption
  (rupture or erosion) leading to platelet
  activation and thrombus formation
• Atherothrombosis is the underlying condition that
  results in events leading to myocardial
  infarction, ischemic stroke, and vascular death

Plaque rupture1
Plaque erosion2
1. Falk E et al. Circulation 1995 92 65771. 2.
Arbustini E et al. Heart 1999 82 26972.
3
The Development of Atherothrombosis a
Generalized and Progressive Process
Adapted from Drouet L. Cerebrovasc Dis 2002
13(suppl 1) 16.
4
Atherothrombosis and Microcirculation
Adapted from Topol EJ, Yadav JS. Circulation
2000 101 57080, and Falk E et al. Circulation
1995 92 65771.
5
Major Clinical Manifestations of Atherothrombosis
Ischemic stroke
Transient ischemic attack
Myocardial infarction

• Angina
• Stable
• Unstable

• Peripheral arterial
• disease
• Intermittent claudication
• Rest Pain
• Gangrene
• Necrosis

Adapted from Drouet L. Cerebrovasc Dis 2002
13(suppl 1) 16.
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Atherothrombosis is aLeading Cause of Death
Worldwide1
Mortality ()
Cardiovascular disease, ischemic heart disease
and cerebrovascular disease Worldwide defined as
Member States by WHO Region (African, Americas,
Eastern Mediterranean, European, South-East Asia
and Western Pacific)
1. The World Health Report 2001. Geneva WHO
2001.
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Identifying Those at Risk of Atherothrombosis1,2

• Local factors
• Elevated prothrombotic factors fibrinogen, CRP,
  PAI-1
• Blood flow patterns, vessel diameter, arterial
  wall structure

• Systemic
• conditions
• History of vascular events
• Hypertension
• Hyperlipidemia
• Hypercoagulable states
• Homocystinemia

Atherothrombosis manifestations (myocardial
infarction, stroke, vascular death)

• Generalised
• disorders
• Obesity
• Diabetes

• Lifestyle
• Smoking
• Diet
• Lack of exercise

• Genetic
• Genetic traits
• Gender
• Age

1. Yusuf S et al. Circulation 2001 104 274653.
2. Drouet L. Cerebrovasc Dis 2002 13(suppl 1)
16.
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Atherothrombosis is a Systemic Disease
Increased Risk of Stroke in Patients After a
Myocardial Infarction1
1. Lichtman JH et al. Circulation 2002 105
10827.
9
Atherothrombosis is a Systemic Disease
Long-Term Risk Increase for Stroke As a Function
of Coronary Calcification1
x 3.3
3.5
3.0
2.5

2.0
Risk increase
1.5
1.0
1.0
0.5
0.0
0100
101500
gt 500
Coronary calcium score
1. Vliegenthart R. Stroke 2002 33 4625.
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Atherothrombosis is a Systemic Disease
Long-term Risk Increase for Myocardial
Infarction as a Function of Carotid Intima Media
Thickness1
4.0
x 3.61
3.5
3.0


2.5
Risk increase
2.0

1.5
1.0
1.0
0.5
0.0
1
2
3
4
5
Quintiles of carotid artery media thickness
1. OLeary DH. N Engl J Med 1999 340 1422.
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Atherothrombosis is a Systemic Disease Increase
for Myocardial Infarction and Stroke as a
Function of ABI Measurement1
2.5
x 2.2
2.0

Risk increase

1.5

1.0
1.0
0.8
0.6
0.4
0.2
Ankle-brachial index (ABI) index
1. Dormandy JA, Creager MA. Cerebrovasc Dis 1999
9(suppl 1) 14.
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Risk Assessment of Further Atherothrombotic
Events in Actual Practice1
Atherothrombotic Events/100 Patients Per Year
1. Caro J. Eur Heart J 2001 22(abstr suppl) 522.
13
Manifestations of Atherothrombosis are Commonly
Found in More than One Arterial Bed in an
Individual Patient1
Data from CAPRIE study (n19,185)
1. Coccheri S. Eur Heart J 1998 19(suppl) P1268.
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Summary

• Atherothrombosis is characterized by a sudden
  plaque disruption leading to platelet activation
  and thrombus formation1
• Atherothrombosis is the common pathological link
  between all major clinical manifestations of
  vascular disease myocardial infarction, ischemic
  stroke and peripheral arterial disease2
• Patients with clinical manifestations of
  atherothrombosis in one vascular bed are not only
  at risk of a recurrent event in the same arterial
  distribution, but also at risk of developing
  ischemic events in other vascular beds3
• Atherothrombosis is one of the leading causes of
  death worldwide4

1. Drouet L. Cerebrovasc Dis 2002 13(suppl 1)
16. 2. Nenci GG. Eur Heart J 1999 1(suppl A)
A27A30. 3. Lichtman JH et al. Circulation 2002
105 10827. 4. The World Health Report
2001.Geneva WHO 2001.
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Disclaimer

• This slide kit presents data to support the
  rationale for the use of ADP-receptor antagonists
  in registered and non-registered indications.
• The slide kit has been prepared for medical and
  scientific purposes, and cannot be considered as
  an inducement to use clopidogrel in
  non-registered indications.
• Neither Sanofi-Synthélabo nor Bristol-Myers
  Squibb recommends the use of clopidogrel in any
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