Aspirin Resistance: Significance, Detection and Clinical Management of This Real Phenomenon

1
Aspirin Resistance Significance, Detection and
Clinical Management of This Real Phenomenon

• Webcast
• May 10th, 2004
• Sponsored by

2
Educational Objectives

• Define Aspirin Resistance, Incidence and
  Prevalence in the Population
• Describe the Mechanisms for Aspirin Resistance
  and Reduced Platelet Inhibition
• Understand the Importance of Aspirin Resistance
  Testing, Methods of Detection
• Understand Clinical Implication and Clinical
  Decisions in Aspirin Resistant Patients

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Faculty

• Steven Steinhubl, M.D.
• Director of Cardiovascular Research and Education
• Associate Professor of Medicine
• University of Kentucky, Lexington, Kentucky
• Daniel I. Simon, M.D.
• Associate Professor of Medicine
• Harvard Medical School
• Associate Director, Interventional Cardiology
• Brigham and Womens Hospital, Boston,
  Massachusetts
• Christopher Cannon, M.D.
• Associate Professor Of Medicine, Harvard Medical
  School
• Senior Investigator, TIMI Study Group
• Associate Physician, Brigham and Womens Hospital
• Boston, Massachusetts

4
Aspirin in Cardiovascular Disease

• Christopher Cannon, M.D.
• Brigham and Womens Hospital
• Boston, MA

5
Vascular Disease in the U.S.
TIA transient ischemic attack. ACS acute
coronary syndrome. PAD peripheral arterial
disease.

• American Heart Association. 2004 Heart Disease
  and Stroke Statistics.
• Brown et al. Amer. Stroke Assoc. 25th Int. Stroke
  Conference. 2000.
• National Stroke Association Press Release. April
  25, 2000.
• Hirsch AT et al. JAMA. 2001286111317-1324.

6
U.S. Heart Disease Doublesin the Next Half
Century
30
24.6
25
20
Number of
15
12.4
Patients
(Millions)
10
5
0
1970
1980
1990
2000
2010
2020
2030
2040
2050
ACC/AHA Guidelines 2001, NHLBI Chartbook 2000
and Foot et al (JACC 2000)
7
Estimated Direct and Indirect Costs of
Cardiovascular Diseases and Stroke
329.2
350
300
250
214
200
Billions2
150
111.8
100
47.2
49.4
50
23.2
0
Heart disease
Stroke
Hypertensive disease
Total CVD3
Congestive heart failure
Coronary Heart disease
1 2002 estimates (USA) 2 American Heart
Association. 2002 Heart and Stroke Statistical
Update. 2001 3 CVD cardiovascular disease
8
Aspirin Usage In the US
Percentage of Use
9
Antithrombotic Trialists Collaboration (ATC)
Efficacy of Antiplatelet Therapy on Vascular
Events
Control better
Antiplatelet better
Vascular events myocardial infarction, stroke
or vascular death
Antithrombotic Trialists Collaboration. BMJ
2002 324 7186.
10
Aspirin in Acute Coronary Syndromes
Acute Myocardial Infarction
15
11.8
9.4
10
5
0
Plac.
ASA
RISC Group.
Lancet
Roux etal.
JACC
ISIS-2.
L
ancet
ISIS-2.
L
ancet
1990336827-30.
199219671-7.
19882349-60.
19882349-60.
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Aspirin in Acute Coronary Syndromes
Primary
Stable
Prevention
Angina
Theroux, etal.
NEJM
Cairns, etal.
NEJM
PHS.
NEJM

Ridker etal.
AJC

19883191105-11.
19853131369-75.
1989321129-35
1991114835-9.
12
Indirect Comparisons of ASA Doses on Vascular
Events in High-Risk Patients
OR
Aspirin Dose No. of Trials ()
Odds Ratio
500-1500 mg 34 19
160-325 mg 19 26
75-150 mg 12 32
Any aspirin 65 23
0.5
1.0
1.5
2.0
0
Odds reduction. Treatment
effect Pacid. Adapted with permission from BMJ
Publishing Group. Antithrombotic Trialists
Collaboration. BMJ. 200232471-86.
Antiplatelet Better
Antiplatelet Worse
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Major Bleeding at 1 year by ASA Dose
CURE
Clopidogrel ASA (N6259)
ASA (N6303)
P-Value

• ASA Dose
• 0.53
• 100-200 mg (N7428) 2.8
  3.4 200 mg (N2301) 3.7
  4.9

Peters RJG, et al. Circulation 20031081682-1687
14
BRAVO Bleeding By ASA dose
Outcomes by Aspirin Dose in Placebo Study Drug
Patients
Low Dose,75-162 mg/d(n2410)
Higher Dose,162-326 mg/d(n2179)
Primary end point 16.4 18.6 Death, MI,
stroke 6.2 6.1 Death 2.8 1.7 MI 2.0 2.1 Stroke 2.1
2.8 Internal bleeding 2.4 3.3 Any
bleeding 11.1 15.4 Transfusion 1.0 2.0
Topol EJ, et al. Circulation. 2003108399-406.
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Aspirin in Cardiovascular Disease

• Aspirin is proven to reduce death, MI, stroke in
  patients with all types of cardiovascular disease
• Inexpensive, widely available
• Dosing now focused on low-dose (75-81 mg) for
  optimal efficacy / safety balance
• However
• Does one dose fit all?
• Is there Aspirin resistance?
• Are their clinical consequences of Aspirin
  resistance?