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1、Introductionto AspirinResistance.May10,2004StevenR.Steinhubl,MDAspirinHistoryFirstsynthesizedinpureformbyFelixHoffmanofFriedr.Bayer&Co.in1897.(FromtheGermanacetylspirsaure+chemicalsuffix–in)AspirinHistoryDuetoproblemswiththeoriginalAspirinpowderbeingcounterfeited
2、,itbecamethefirstpharmaceuticalagenteversoldinpillforminearly1900’s.FirstpillinUSAwas5grains(~325mg).MetabolicPathwaysofArachadonicAcidMembranePhospholipidsARACHIDONICACIDProstaglandinH2COX-1ThromboxaneA2?PlateletAggregationVasoconstrictionProstacyclin?PlateletAg
3、gregationVasodilitationAspirinAspirinintheTreatmentofACSWallentinLC,etal.JACC1991;18:1587-93.0.000.050.100.150.200.25036912MonthsProbability ofDeathorMIPlaceboAspirin75mgRiskratio0.52 95%CL0.37-0.72AspirininAcuteMyocardialInfarction:ISIS-2100200300400500600071421
4、2835Placeboalone:568/4300(13.2%)Aspirinalone:461/4295(10.7%)Streptokinasealone:448/4300(10.4%)Streptokinaseplusaspirin:343/4292(8.0%)CumulativeNumberofVascularDeathsDaysFromRandomizationRandomizedTrialsofAspirininPTCASchwartz,NEnglJMed1988;318:1714White,CoronaryA
5、rteryDisease1991;2:75704812SchwartzetalN=376WhiteetalN=337%MajorIschemicComplications6.912.6Heparin10,000units2.4Ticlopidine+Heparin1.6ASA/Dipyridamole+Heparin77%P=0.01133.275%P<0.001Whatis“AspirinResistance?”InabilityofASAtopreventtreatedpatientsfromhavingthromb
6、oticevents.InabilityofASAtherapytoprolongbleedingtime.InabilityoftreatmentwithASAtopreventthromboxanebiosynthesis.InabilityofASAtoachieveapre-definedeffectonanexvivoorinvitromeasureofplateletfunction.PatronoC.JThrombHaemost2003;1:1710-3Inter-IndividualVariability
7、inResponsetoAspirinQuickAJ.AmericanJournalofMedicalScienceSept1966:265-9N=10InterpatientVariabilityinAspirinResponse-BleedingTimeAspirin,325mgdailyin40CABGpatientsBuchanan,CanJCardiol1995;11(3):221100300500700900100300500700900BleedingTime,Pre-ASABleedingTimePost
8、-ASAResponders(58%)MeanBT?58+10%Non-responders(42%)MeanBT?2+4%AspirinResponsivenessand ClinicalOutcome181patients,followingCVA.Aspirin500mgTID.Followed-upfor24
