阿司匹林抵抗与临床预后课件

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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,2020年10月2日,*,Daniel I.Simon,M.D.,Associate Director,Interventional Cardiology,Brigham and Womens Hospital,Associate Professor of Medicine,Harvard Medical School,Boston,MA USA,ASA Resistance andClinical Outcomes,2020年10月2日,1,Daniel I.Simon,M.D.ASA Resis,ASA Resistance:Key Questions,Does a standardized definition exist?,Are there reliable tests to diagnose this phenomenon?,What are the possible mechanisms and future implications?,Does it have any clinical significance?,How do we manage patients with Aspirin resistance?,2020年10月2日,2,ASA Resistance:Key QuestionsD,Established Platelet Function Tests,Harrison P.,Br J Hematology,2000;111:733-744,Platelet Function Test,Bleeding time,Aggregometry-turbidometric methods,Aggregometry-impedance methods,Aggregometry&luminescence,Adenine nucleotides,Thromboelastography(TEG),Glass filterometer,Platelet release markers,In Vivo screening test,Responsiveness to panel agonists,Responsiveness to panel agonists,Combined aggregation and ADP release,Stored and released ADP,Global Hemostasis,High shear platelet function,In vivo platelet activation markers,Advantages,Physiological,Diagnostic,Whole blood test,More information,Sensitive,Predicts bleeding,Simple,Simple,systemic,measure of platelet,activation,Disadvantages,Insensitive,invasive&high variability,Labor intensive&non-physiological,Insensitive,Semi-quantitative,Specialized equipment,Measures clot properties,only,insensitive to ASA,Requires blood counter,Prone to artifact,Plt Function Test,Disadvantages,Advantages,Assay,2020年10月2日,3,Established Platelet Function,Newer Platelet Function Tests,(PFA)-100 Whole blood+Primary Limited range-most pts,hemostasis after GP IIb/IIIa inhibitors have,(high shear closure times 300 sec,so may,adhes/aggreg)not be able to discern diff.Used to assay ADP antagonist,Clot Signature Whole blood +Adhesion,Large instrument for routine use,Analyzeraggregation and interpretation of results is,complex,Rapid platelet Whole blood +Aggregation GP IIb/IIa:baseline sample req.,function assay Clinical outcome data(GOLD),Aspirin:AA-like agonist,Harrison P.,Br J Hematology,2000;111:733-744,Mukherjee D&Moliterno DJ.,Clin Pharmacokinet,2000;39(,6):445-458,Flow cytometry,Whole blood -Platelet GP,Flexible&powerful.Requires,activation markers,specialized operator.Expensive,Platelet function,AssaySubstrate BedsidePrincipleComments,2020年10月2日,4,Newer Platelet Function Tests(,Prevalence of ASA Resistance,Gum PA et al.,Am J Cardiol,2001;88:230-235,ASA-R:mean aggregation,70%with M 10 ADP&,20%with 0.5 mg/ml AA,325 patients with stable CVD taking ASA 325 mg 7days,2020年10月2日,5,Prevalence of ASA Resistance G,Wang JC et al.,Amer J Cardiol,2003;92:1492-4,422 patients presenting to cardiac cath lab on ASA 81-325 mg 7d,Prevalence of Aspirin Resistance,23.4%Aspirin non-responsive,Accumetrics VerifyNow Aspirin,Definition:ARU 550,Multivariate analysis:history of CAD associated with twice the odds of being ASA non-responder(odds ratio 2.09,95%CI 1.189-3.411,p=0.009),No association with gender,DM,smoking,ASA dose,2020年10月2日,6,Wang JC et al.Amer J Cardiol,Clinical Studies,2020年10月2日,7,Clinical Studies2020年10月2日7,ASA Resistance:Long-term Clinical Studies,Stroke,1,1500 mg Plt Reactivity 24 mStroke/MI/10-fold lower,(n=180)Vascular death risk in ASA responders,PVD,2,100 mg Whole blood 18 m Arterial 87%higher r,isk,(n=100)aggregometry Occlusion in,ASA-R,CVD/CVA,3,100 mg PFA-1060 mRecurrent CVA/Recurrent CVA 34%,(n=53)TIA TIA ASA-R vs.0%no,recurrent events,Subgroup 75-325 mg Urinary 11-dehydro 5 yrs MI/Stroke/1.8 times,HOPE,4,TX B2 CVDeath higher risk in,(n=967),upper vs.lower quartile,CVD,5,325 mg Optical platelet 679185 Death/MI/CVA 24%ASA-R vs.,(n=326)aggregation days 10%ASA-S HR 3.12(95%CI 1.1-8.9,p=0.03),Grotemeyer KH,et al.,Thromb Res,1993,;,71:397-403,Mueller MR,et al.Thromb Haemost 1997;78:1003-1007,Grundmann K,et al.,J Neurol,2003;250:63-66,Eikelboom JW,et al.,Circulation,2002;105:1650-1655,Gum PA,et al.,J Am Coll Cardiol,2003;41:961-965,PtsASA doseTestF/UEnd-pointResults,2020年10月2日,8,ASA Resistance:Long-term Clin,ASA Resistance and Clinical Outcome in CAD Patients,Eikelboom JW,et al.,Circulation,2002;105:1650-1655,HOPE Trial Substudy:ASA 75-325 mg,2020年10月2日,9,ASA Resistance and Clinical Ou,ASA Resistance and Clinical Outcome in CVD Patients,Gum PA,et al.,J Am Coll Cardiol,2003;41:961-965,ASA-R:mean aggregation,70%with 10 M ADP&20%with 0.5 mg/ml AA,326 CVD patients on ASA 325 mg,7 days,p=0.03,2020年10月2日,10,ASA Resistance and Clinical Ou,ASA Resistance and Clinical Outcome in PVD Patients,Mueller MR et al.,Thromb Haemost,1997;78:1003-1007,2020年10月2日,11,ASA Resistance and Clinical Ou,ASA Resistance and Clinical Outcome in Stroke Patients,Grotemeyer KH et al.,Thromb Res,1993,;,71:397-403,2020年10月2日,12,ASA Resistance and Clinical Ou,ASA Resistance and Clinical Outcome in Stroke Patients,Grundmann K et al.,J Neurol,2003;
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