心房颤动抗栓治疗进展.ppt

心房颤动抗栓治疗进展,北京大学人民医院心脏中心孙艺红,TheEpidemiologyofAFinChinaandotherCountries,5.5%,5.4%,PatientswithAFInChina8million,TheEpidemicofAtrialFibrillation,IncreasingprevalenceofriskfactorsforAF:OlderageSystemichypertensionHeartfailureValvularheartdiseaseDiabetesmellitusObesity,PrevalenceofStrokeinPatientswithNVAFStratifiedbyAge,years,0,5,10,15,20,25,Prevalence(%),30,40,4049,6069,50-59,7079,80,HUD,etal.ChinJInternMed,2003;42:157-161,EfficacyofWarfarininAtrialFibrillation,TheCovalentGroup,Inc.,CombinedEndpointOccurrence(%),Follow-up（m）,0,6,12,18,24,0,20,15,10,5,Aspirin(150-160mg)Warfarin(INR2.0-3.0),RRR36%,13.0%,8.4%,NetClinicalOutcome,TheRandomizedProspectiveTrialcomparedaspirinwithadjusteddosewarfarininNVAFPatients,P=0.01,Theoptimalintensityofanticoagulation,4.0INR,EmbolicHemorrhage,43.53.02.52.01.51.00.50,INR2-3,AnticoagulationofAFinReal-life,100908070605040302010,53.5%,9.8%,37.0%,43.7%,8.9%,47.3%,NoantithromboticWarfarinaspirin,Eligible*(n=3944),Ineligible(n=562),*patientswithatleastonehigh-moderateriskfactorsaccordingtoACC/AHAguideline2006,TheAbsoluteIncidenceofBleeding,Hemorrhageofin-hospitalpatientswithNVAFinChina,HuD,etal.2004ChinJInternMed,P=0.001,WARFARINASPIRINNO,1.4%,6.3,3.3%,MINOR（5.3%）MAJOR（1%）,%,987654321,TheDilemmaofAnticoagulationManagement,Warfarinhasanarrowtherapeuticwindowofeffectivenessandsafety.Manyfactorsinfluenceapatientsstabilityinthatwindow.Frequentmonitoringisrequiredtomaintainpatientsinthetherapeuticwindow.Monitoringislaborintensiveandcomplex.Physiciansavoidwarfarinusebecauseofitscomplexity.,BalancingRiskandBenefit,ImproveriskstratificationImproveanticoagulationcontrolMinimizeuseofconcomitantantiplatelettherapyNewantithrombotictherapies,BalancingRiskandBenefit,Improveriskstratification,RelativeDistributionofPatientsbyapplyingdifferentriskstratificationschemes,Thestratificationschemeswereappliedtoastratifiedrandomsampleof1000patientswasselectedfromStrokePreventioninAtrialFibrillationIIIparticipants22,23,BalancingRiskandBenefit,ImproveriskstratificationImproveanticoagulationcontrol,VariableDoseResponse,DruginterferenceMostpotent:Amiodarone(inhibitsR-andS-enantiomers)Mostunder-appreciated:Paracetamol(toutedinterferencewithenzymesofthevitaminKcycle)DietaryvitaminK,ThispathwayillustratesgenesthoughttomediatetheeVectsofwarfarin.Italsodepictsasimpli-WedrepresentationofthebiotransformationofwarfarinandvitaminK,Associationofwarfarindosewithgenesinvolvedinitsactionandmetabolism,VKORC1RelatedtoDoseofWarfarin,J.Med.Genet.publishedonline12Apr2006;,Patientswithhomozygousofthedoseofwarfarindoubled（27mg/w47mg/w）,GENOTYPEVSSTANDARDWARFARINDOSINGCouma-GenTrial(N=206),RapidturnaroundCYP2C9andVKORC1testingvs.“empiric”Primaryendpoint:TTRSmallerandfewerdosingchangeswithgenetictestingNodifferenceinTTR,Circulation2007;116:2563-2570,PiechartshowingtheknownsourcesofvariabilityinwarfarindoseneededforastableINR.Eachestimateisbasedonasummaryanalysisofpartialr2valuesfrommultivariateregressionanalysisreportedinsixstudiesthatincludedgenotypingonbothCYP2C9andVKORC1,FactorsContributetoStableDoseWarfarin,OBJECTIONSTOGENETICTESTING:Warfarin,1.Consideredcostly,inconvenient.(CoveragebyCMSjustshiftscosts.)2.Slowsdownprescribingwarfarin.3.Notproventobeasgoodorsuperiortothecurrentstandardofcare(“educatedguess”approach)whichisgettingbetter.4.Willgeneticprofilingimprovemaintenancedosing?Ifso,how?5.CanAnticoagClinics/POCtestingimprovewarfarinanticoagulationmorethanrapidturnaroundgenetictesting?6.Novelanticoagulantsfixeddose,nocoagulationmonitoring,ModelsofACManagement,Routinemedicalcareorusualcare(UC)1Anticoagulationcliniccare(ACC)1Point-of-care(POC)testing2ProvidertestinganddosingPatientself-testing(PST),butDosingbyproviderPatientself-management(PSM),withDosingbypatient,BalancingRiskandBenefit,ImproveriskstratificationImproveanticoagulationcontrolMinimizeuseofconcomitantantiplatelettherapy,Recommendationofpatientswithindicationsoflong-termoralanticoagulationafterPCI,BalancingRiskandBenefit,ImproveriskstratificationImproveanticoagulationcontrolMinimizeuseofconcomitantantiplatelettherapyNewantithrombotictherapies,左心耳堵闭术取代药物抗凝？,PLAATO,Watchman,Newanticoagulants,新型抗凝药物,ComparisonofidraparinuxwithvitaminKantagonistsforpreventionofthromboembolism-Kaplan-Meier,firstconfirmedsymptomaticrecurrentstrokeornon-CNSsystemicembolism,Firstclinicallyrelevantbleedingduringtherandomisedtreatmentperiod,Lancet2008;371:31521,stopafterrandomisationof4576patients,meanfollow-upperiodof107,新型抗凝药物-利伐沙班,ACC/AHA心房颤动指南2006,结论,心房颤动是卒中的重要危险因素。中高危房颤患者，监测下调整剂量华法林（INR2.0-3.0），中国人同样适用；但多数AF患者没有进行抗凝治疗。房颤抗栓策略选择：血栓/出血的平衡。新型抗凝药物可能是未来抗凝的方向，简便、无需监测。长期抗凝治疗管理，建立抗凝门诊。,谢谢,抗凝治疗的管理,抗凝门诊1患者手提式自我监测仪2,3计算机辅助4,5,1ArchInternMed1998;158:1641-72ThrombHaemost2000;839:661-53Lancet2000;356:97-1024Lancet1998;352:1505-95ThrombHaemost2000;83:849-52,严重出血的发生率,13559名房颤病人颅内出血的发生率,JAmGeriatrSoc2006;54:1231-1236,年龄服华法林事件数（n）率（95%CI）未服华法林事件数（n）率（95%CI）,服华法林未服华法林,年事件发生率（%）,血栓栓塞和出血事件与INR,4.0INR,血栓栓塞出血,43.53.02.52.01.51.00.50,接受华法林治疗的房颤病人发生严重出血的危险因素：HEMORR2HAGES,AmHeartJ2006;151:713-719,肝、肾疾病1酒精滥用1恶性肿瘤1老年1血小板计数减少1再次出血危险2高血压1贫血1遗传因素-额外的跌倒危险1中风1,ACC/AHA心房颤动指南2006,类推荐除孤立性房颤和有禁忌证外，所有房颤患者均建议服用抗栓药物以预防血栓栓塞。（A）抗栓药物的选择根据卒中和出血的绝对危险，对患者的相对危险和获益。（A）监测INR频率：初始用药时至少每周一次，稳定后每月一次。（A）因手术需要中断抗凝治疗超过1周以上的高危患者，给与普通肝素或低分子肝素替代，尽管这些替代治疗的疗效还不确定。（bC）,芬兰6家医院2003-2004调查,EuropeanHeartJournal(2007)28,726732,房颤患者进行PCI的抗栓治疗,GregoryY.H.LipandManasKarphaChest2006;130;1823-1827,INR异常升高的处理建议,治疗与研究方向,Moderate-riskfactorsHigh-riskfactorsage75previousstrokehypertensionmitralvalvestenosisHeartfailureprostheticheartvalvediabetes,PreventingThromboembolismRiskcategoryrecommendedtherapyNoriskfactorsASA81-325mgQDOnemoderateriskfactorASA81-325QDorwarfarinAnyhigh-riskfactorOr1moderate-riskfactorWarfarin,ACTIVE研究设计,DocumentedAF+1riskfactor:Age75,Hypertension,Priorstroke/TIA,LVEF10mm），形态，原位二尖瓣，活动，密度低二尖瓣多于主动脉瓣预防病因治疗：迅速和有效的抗生素治疗抗血小板药物能减少赘生物体积没有抗凝治疗的适应证正在应用口服抗凝治疗者，改用肝素,其他心源性卒中的预防,主动脉弓动脉粥样硬化病变相关的卒中患者，抗血小板治疗。（1C+）原因不明缺血性卒中患者，如果合并卵圆孔未闭，推荐抗血小板治疗；（1C+）有TIA或卒中病史的二尖瓣脱垂患者，建议抗血小板治疗。（1C+）人工瓣膜置换术后，华法林抗凝（INR2.5-3.5），根据瓣膜的位置和种类。,ACCP2004抗栓和溶栓指南,RiskfactorsforAFpatientsonwarfarin：HEMORR2HAGES,AmHeartJ2006;151:713-719,肝、肾疾病1酒精滥用1恶性肿瘤1老年1血小板计数减少1再次出血危险2高血压1贫血1遗传因素-额外的跌倒危险1中风1,NHLBIRandomizedControlledTrial:2008-2011,PrimaryEndpoint:PercentofTimeinTherapeuticRange(PTTR)Hypothesis:60%PTTRinstandardarmversus72%PTTRinGeneticsPlusClinicalNomogramarm,RISKFACTORSFORANELEVATEDINR(ItsnotallGenetics),AdvancedAge(one-thirddose)AbnormalLiverFunctionDecreasedVitaminKIntake(NPO,diarrhea,antibiotics)AlcoholinBingesChangeinWarfarinPreparationDrug-druganddrug-foodinteractions,BRIDGINGTRIAL(N=1,293),Prospectivecohort;allreceivinglong-termwarfarin;averageage:72years;mostlyAFpatients80%hadwarfarinheld5days0.7%hadthromboembolism;nonehadbeenbridged;0.4%ratewhenwarfarinwasheld76yrs,Hypertension,Diabetes,LAthrombi,SBP,1.76(1.08-2.89),1.52(1.28-1.80),1.39(1.11-1.76),1.71(1.21-2.28),1,2,3,4,5,2.77(1.25-6.13),HUD,etal.ChinJInternMed,2003;42:157-161,VariableDoseResponse,Geneticpolymorphisms:cytochromeP450CYP2C9andVKORC1(vitaminKepoxidereductasecomplex1)DiseaseStates,e.g.,CHF,malignancyPharmacodynamicchangeswithaging,Age40-80,ASPIRIN150-160mg,WARFARININR2.0-3.0,Secondaryendpoit:lacunarinfarction,peripheralar