阿司匹林抵抗课件.ppt
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1、Introduction to Aspirin Resistance.May 10,2004Steven R.Steinhubl,MDAspirin HistoryFirst synthesized in pure form by Felix Hoffman of Friedr.Bayer&Co.in 1897.Aspirin HistoryDue to problems with the original Aspirin powder being counterfeited,it became the first pharmaceutical agent ever sold in pill
2、form in early 1900s.First pill in USA was 5 grains(325 mg).Metabolic Pathways ofArachadonic AcidMembrane PhospholipidsARACHIDONIC ACIDProstaglandin H2COX-1Thromboxane A2-Platelet Aggregation-VasoconstrictionProstacyclin-Platelet Aggregation-VasodilitationAspirin in the Treatment of ACSWallentin LC,e
3、t al.JACC 1991;18:1587-93.0.000.050.100.150.200.25036912MonthsProbabilityof Death or MIPlaceboAspirin 75 mgRisk ratio 0.5295%CL 0.37-0.72Aspirin in Acute Myocardial Infarction:ISIS-21002003004005006000714212835Placebo alone:568/4300(13.2%)Aspirin alone:461/4295(10.7%)Streptokinase alone:448/4300(10.
4、4%)Streptokinase plus aspirin:343/4292(8.0%)Cumulative Number of Vascular DeathsDays From RandomizationRandomized Trials of Aspirin in PTCASchwartz,N Engl J Med 1988;318:1714 White,Coronary Artery Disease 1991;2:75704812Schwartz et alN=376White et alN=337%Major Ischemic Complications6.912.6Heparin 1
5、0,000 units2.4Ticlopidine+Heparin1.6ASA/Dipyridamole+Heparin77%P=0.01133.275%P0.001What is“Aspirin Resistance?”lInability of ASA to prevent treated patients from having thrombotic events.lInability of ASA therapy to prolong bleeding time.lInability of treatment with ASA to prevent thromboxane biosyn
6、thesis.lInability 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;1:1710-3Inter-Individual Variability in Response to AspirinQuick AJ.American Journal of Medical Science Sept 1966:265-9N=10Interpatient Variability in Aspir
7、in Response-Bleeding TimeAspirin,325 mg daily in 40 CABG patientsBuchanan,Can J Cardiol 1995;11(3):221 100 300 500 700 900100300500700900Bleeding Time,Pre-ASABleedingTimePost-ASAResponders(58%)Mean BT 58+10%Non-responders(42%)Mean BT 2+4%Aspirin Responsiveness and Clinical Outcome181 patients,follow
8、ing CVA.Aspirin 500 mg TID.Followed-up for 24 months.10075506121824%of Patients Without EventMonths of ObservationAspirin RespondersN=114Aspirin Non-respondersN=6060%95%P0.0001Grotemeyer,Thrombosis Research 1993;71:397Thromboxane Biosynthesis on Aspirin and CV Events1.01.31.41.8012 33.8Uninary 11-de
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