文档介绍：Introduction to Aspirin Resistance.
May 10, 2004
Steven R. Steinhubl, MD
Aspirin History
First synthesized in pure form by Felix Hoffman of Friedr. Bayer & Co. in 1897.
(From the German acetylspirsaure + chemical suffix – in)
Aspirin History
Due to problems with the original Aspirin powder being counterfeited, it became the first pharmaceutical agent ever sold in pill form in early 1900’s.
First pill in USA was 5 grains (~325 mg).
Metabolic Pathways of Arachadonic Acid
Membrane Phospholipids
ARACHIDONIC ACID
Prostaglandin H2
COX-1
Thromboxane A2
Platelet Aggregation
Vasoconstriction
Prostacyclin
Platelet Aggregation
Vasodilitation
Aspirin
Aspirin in the Treatment of ACS
Wallentin LC, et al. 1991;18:1587-93.
0
3
6
9
12
Months
Probability of Death or MI
Placebo
Aspirin 75 mg
Risk ratio 95% CL -
Aspirin in Acute Myocardial Infarction: ISIS-2
100
200
300
400
500
600
0
7
14
21
28
35
Placebo alone:
568/4300 (%)
Aspirin alone:
461/4295 (%)
Streptokinase alone:
448/4300 (%)
Streptokinase plus aspirin:
343/4292 (%)
Cumulative Number of Vascular Deaths
Days From Randomization
Randomized Trials of Aspirin in PTCA
Schwartz, N Engl J Med 1988;318:1714 White, Coronary Artery Disease 1991;2:757
0
4
8
12
Schwartz et al
N=376
White et al
N=337
% Major Ischemic
Complications
Heparin 10,000 units
Ticlopidine + Heparin
ASA / Dipyridamole + Heparin
77%
P=
75%
P<
What is “Aspirin Resistance?”
Inability of ASA to prevent treated patients from having thrombotic events.
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 on an ex vivo or in vitro measure of platelet function.
Patrono C. J Thromb Haemost 2003;1:1710-3
Inter-Individual Variability in Response to Aspirin
Quick AJ.
American Journal of Medic