Aspirin alone: 461/4295 (10.7%) Streptokinase alone: 448/4300 (10.4%)
Streptokinase plus aspirin: 343/4292 (8.0%)
7
14
21
28
35
7
Days From Randomization
Randomized Trials of Aspirin in PTCA
COX-1 Aspirin
Prostaglandin H2
Thromboxane A2
- Platelet Aggregation
Prostacyclin
- Platelet Aggregation
- Vasoconstriction
- Vasodilitation
2020年10月2日
5
Aspirin in the Treatment of ACS
First synthesized in pure form by Felix Hoffman of Friedr. Bayer & Co. in 1897.
2020年10月2日
2
Aspirin History
Due to problems with the original Aspirin powder being counterfeited, it became the first pharmaceutical agent ever sold
Introduction to Aspirin Resistance.
May 10, 2004 Steven R. Steinhubl, MD
2020年10月2日1Fra bibliotekAspirin History
(From the German acetylspirsaure + chemical suffix – in)
0.25 0.20
Probability of Death or MI
0.15
0.10 0.05
0.00
0
3
2020年10月2日
Wallentin LC, et al. JACC 1991;18:1587-93.
Placebo
Aspirin 75 mg
Risk ratio 0.52 95% CL 0.37-0.72
95%
Aspirin Responders N=114
75
P<0.0001
60%
Aspirin Non-responders
Inability of ASA therapy to prolong bleeding time. Inability of treatment with ASA to prevent
thromboxane biosynthesis. Inability of ASA to achieve a pre-defined effect
N=376
Schwartz, N Engl J Med 1988;318:1714
75% P<0.001
3.2 2.4
White et al N=337
8
White, Coronary Artery Disease 1991;2:757
What is “Aspirin Resistance?”
Inability of ASA to prevent treated patients from having thrombotic events.
N=10
2020年10月2日
Quick AJ.
American Journal of Medical Science
Sept 1966:265-9
10
Interpatient Variability in Aspirin Response - Bleeding Time
Aspirin, 325 mg daily in 40 CABG patients
11
Aspirin Responsiveness and Clinical Outcome
181 patients, following CVA. Aspirin 500 mg TID. Followed-up for 24 months.
% of Patients Without Event
100
900
700
Bleeding Time 500
Post-ASA
300
100
100 300 500 700 900
Bleeding Time, Pre-ASA
2020年10月2日
Buchanan,Can J Cardiol 1995;11(3):221
Responders (58%) Mean BT 58 + 10 % Non-responders (42%) Mean BT 2 +4 %
on an ex vivo or in vitro measure of platelet function.
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Patrono C. J Thromb Haemost 2003;1:1710-3
Inter-Individual Variability in Response to Aspirin
in pill form in early 1900’s. First pill in USA was 5 grains (~325 mg).
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Metabolic Pathways of Arachadonic Acid
Membrane Phospholipids
ARACHIDONIC ACID
6
9
Months
12
6
Aspirin in Acute Myocardial Infarction: ISIS-2
Cumulative Number of Vascular Deaths
600 500 400 300 200 100
0
2020年10月2日
Placebo alone: 568/4300 (13.2%)
% Major Ischemic Complications
12
12.6
Heparin 10,000 units ASA / Dipyridamole + Heparin Ticlopidine + Heparin
8 6.9
4
77%
P=0.0113
1.6 0
Schwartz et al
2020年10月2日