Transcript Document

Aspirin Resistance:
Significance, Detection and
Clinical Management of This
Real Phenomenon
Webcast
May 10th, 2004
Sponsored by
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
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 Women’s Hospital, Boston, Massachusetts

Christopher Cannon, M.D.
Associate Professor Of Medicine, Harvard Medical School
Senior Investigator, TIMI Study Group
Associate Physician, Brigham and Women’s Hospital
Boston, Massachusetts
Aspirin in
Cardiovascular Disease
Christopher Cannon, M.D.
Brigham and Women’s Hospital
Boston, MA
Vascular Disease in the U.S.
Annual
Incidence
(Millions)
Prevalence
(Millions)
1
Stroke
0.70
TIA
0.50
ACS
1.7 *
14.2
PAD

8–12
2
1
TIA = transient ischemic attack. ACS = acute coronary syndrome.
PAD = peripheral arterial disease.
1.
2.
3.
4.
1
4.7
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. 2001;286:11:1317-1324.
3
4.9
1†
4
U.S. Heart Disease Doubles
in the Next Half Century
30
24.6
25
20
Number of
Patients 15
(Millions)
12.4
10
5
0
1970
1980
1990
2000
2010
2020
2030
ACC/AHA Guidelines 2001, NHLBI Chartbook 2000 and Foot et al (JACC 2000)
2040
2050
Estimated Direct and Indirect Costs of
Cardiovascular Diseases and Stroke
$329.2
$350
$300
Billions2
$250
$214
$200
$150
$111.8
$100
$49.4
$47.2
$50
0
$23.2
Heart disease Coronary
Heart
disease
Stroke
1
2002 estimates (USA)
2
American Heart Association. 2002 Heart and Stroke Statistical Update. 2001
3
CVD = cardiovascular disease
Hypertensive
disease
Congestive Total CVD3
heart failure
Aspirin Usage In the US
Percentage of Use
40%
26,000,000 Americans receive
chronic aspirin therapy for
cardioprotection.
37.6
30%
23.3
20%
13.8
10%
12.2
14.1
0
Heart
Disease
Arthritis
Headache
Body
Ache
Other
Antithrombotic Trialists’ Collaboration (ATC):
Efficacy of Antiplatelet Therapy on Vascular Events
Category
% Odds Reduction
Acute myocardial infarction
Acute stroke
Prior myocardial infarction
Prior stroke/transient ischemic attack
Other high risk
Coronary artery disease
(e.g. unstable angina, heart failure)
Peripheral arterial disease
(e.g. intermittent claudication)
High risk of embolism (e.g. atrial fibrillation)
Other (e.g. diabetes mellitus)
All trials
0.0
0.5
1.0
Antiplatelet better
*Vascular events = myocardial infarction, stroke or vascular death
Antithrombotic Trialists’ Collaboration. BMJ 2002; 324: 71–86.
1.5
2.0
Control better
Aspirin in Acute Coronary
Syndromes
Unstable
Angina
Acute Myocardial Infarction
30
20
% of Patients
17.1
4
25
15
3.3
15
11.8
3
20
10
1.9
2
6.5
9.4
10
11
10
5
5
1
0
Plac.
ASA
RISC Group. Lancet
1990;336:827-30.
0
Plac.
ASA
Roux etal. JACC
1992;19:671-7.
0
Plac.
ASA
ISIS-2. Lancet
1988;2:349-60.
0
Plac.
ASA
ISIS-2. Lancet
1988;2:349-60.
Aspirin in Acute Coronary
Syndromes
Primary
Prevention
2.5
Stable
Angina
15
15
2.2
Unstable Angina
15
12.9
12.9
11.9
% of Patients
2
10
10
10
1.3
1.5
6.2
1
3.9
5
5
5
3.3
0.5
0
0
0
Plac.
ASA
PHS. NEJM
1989;321:129-35
Plac.
ASA
Ridker etal. AJC
1991;114:835-9.
0
Plac.
ASA
Cairns, etal. NEJM
1985;313:1369-75.
Plac.
ASA
Theroux, etal. NEJM
1988;319:1105-11.
Indirect Comparisons of ASA Doses on Vascular
Events in High-Risk Patients
Aspirin Dose
OR*
No. of Trials (%)
500-1500 mg
34
19
160-325 mg
19
26
75-150 mg
12
32
<75 mg
3
13
Any aspirin
65
23
0
Odds Ratio
0.5
1.0
1.5
2.0
* Odds reduction.
Antiplatelet Better
Antiplatelet Worse
Treatment effect P<.0001.
ASA, acetylsalicylic acid.
Adapted with permission from BMJ Publishing Group. Antithrombotic Trialists’ Collaboration.
BMJ. 2002;324:71-86.
CURE
Major Bleeding at 1 year by ASA Dose
ASA
Clopidogrel
+ ASA
(N=6303)
(N=6259)
P-Value
ASA Dose:
<100 mg (N=1927)
1.9%
3.0%
100-200 mg (N=7428)
2.8%
3.4%
>200 mg (N=2301)
3.7%
4.9%
Peters RJG, et al. Circulation 2003;108:1682-1687
0.53
BRAVO: Bleeding By ASA dose
Outcomes by Aspirin Dose in Placebo Study Drug Patients
Low Dose,
75-162 mg/d
(n=2410)
Higher Dose,
162-326 mg/d
(n=2179)
Primary end point
Death, MI, stroke
Death
MI
Stroke
16.4
6.2
2.8
2.0
2.1
18.6
6.1
1.7
2.1
2.8
Internal bleeding
Any bleeding
Transfusion
2.4
11.1
1.0
3.3
15.4
2.0
Topol EJ, et al. Circulation. 2003;108:399-406.
Aspirin in Cardiovascular Disease
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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…
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Does one dose fit all?
Is there Aspirin resistance?
Are their clinical consequences of Aspirin resistance?