慢性稳定性心绞痛的治疗.ppt

GUIDELINESFORTHEMANAGEMENTOFCHRONICSTABLEANGINA,AmericanCollegeofCardiology,PuertoRicoChapter,February6,2007,GAP,TheGoalsofTherapyinCAD,Toimprovequalityoflife(symptoms)ToreducemortalityToreducemorbidityToreduceprogressionofdiseaseandinduceregression.,TreatmentofChronicStableAngina,Medical,Revascularization,PCI,ACBG,MEDICALTHERAPY,ANTIPLATELETSBETABLOCKERSNITRATESCALCIUMANTAGONISTACEISTATINSNEWTHERAPIES,ANTIPLATELETAGENTS,ASAPhysiciansHealthStudySwedishAnginaPectorisTrialTICLOPIDINECLOPIDOGRELCAPRICURE,ReceptorGPIIb-IIIa:TheFinalCommonPathwaytoPlateletAggregation,WhiteHD.AmJCardiol1997;80:2B-10B.SchaferA.JClinInvest1986;78:73-79.DeJongMJ,etal.CriticalCareNursingClinofNAm1999;11:355-371.MoserM,etal.JCardiovascPharmacol2003;41:586-592.PhillipsDR,ScarboroughRM.AmJCardiol1997;80(4A):11B-20B.,GPIIb-IIIainhibitorsdisplacefibrinogeninexistingthrombitodisaggregatethrombusandpreventfurtherplateletcross-linkingandthrombosis,GPIIb-IIIainhibitorspreventplateletactivationbyblockingGPIIb-IIa(outside-insignaling),High-doseheparinstimulatesPAFwhichactivatesplatelets,PHYSICIANSHEALTHSTUDY,Arandomized,double-blind,placebocontrolledtrialdesignedtotesttheeffectsoflow-doseaspirinandbeta-caroteneintheprimarypreventionofCVDandcanceramong22,071USmalephysicians,aged40to84atbaselinein1982.Baselinebloodspecimenswerecollectedandfrozenforlateranalysesfrom14,916participants.Usinga2x2factorialdesign:325mgofaspirin(Bufferin,suppliedbyBristol-MyersProductsonalternatedays)50mgofbeta-carotene(Lurotin,suppliedbyBASFAGonalternatedays),PHYSICIANSHEALTHSTUDY,TotalcancerProstatecancerCardiovasculardiseaseEyediseaseCataractMaculardegeneration,PrimaryEndpoints,PHYSICIANSHEALTHSTUDY,ThetrialsDataandSafetyMonitoringBoardstoppedtheaspirinarmofthePHSseveralyearsaheadofschedulebecauseitwasclearthataspirinhadasignificanteffectontheriskofafirstmyocardialinfarction.AsreportedintheJuly20,1989NewEnglandJournalofMedicine,aspirinreducedtheriskoffirstmyocardialinfarctionby44%(Plessthan0.00001).Thereweretoofewstrokesordeathsuponwhichtobasesoundclinicaljudgmentregardingaspirinandstrokeormortality,PharmacotherapyforChronicStableAngina(classI),1.AspirinintheabsenceofcontraindicationsA2.Beta-blockersasinitialtherapyintheabsenceofcontraindicationsinpatientswithpriormyocardialinfarctionorwithoutpriormyocardialinfarctionA,B3.ACEinhibitorinallpatientswithCADwhoalsohavediabetesand/orLVsystolicdysfunctionA4.LDL-loweringtherapyinpatientswithdocumentedorsuspectedCADandLDLcholesterol130mg/dl,withatargetLDLof100mg/dlA5.SublingualnitroglycerinornitroglycerinsprayfortheimmediatereliefofanginaB6.Calciumantagonistsorlong-actingnitratesasinitialtherapyforreductionofsymptomswhenbetablockersarecontraindicatedB7.Calciumantagonistsorlong-actingnitratesincombinationwithbetablockerswheninitialtreatmentwithbetablockersisnotsuccessfulB8.Calciumantagonistsandlong-actingnitratesasasubstituteforbetablockersifinitialtreatmentwithbetablockersleadstounacceptablesideeffects,PharmacotherapyforChronicStableAngina(classIIa),1.Clopidogrelwhenaspirinisabsolutelycontraindicated2.Long-actingnon-dihydropyridinecalciumantagonistsinsteadofbetablockersasinitialtherapyB3.InpatientswithdocumentedorsuspectedCADandLDLcholesterol100129mg/dl,severaltherapeuticoptionsareavailable:Ba.Lifestyleand/ordrugtherapiestolowerLDLto100mg/dlb.Weightreductionandincreasedphysicalactivityinpersonswiththemetabolicsyndromec.Institutionoftreatmentofotherlipidornon-lipidriskfactors;consideruseofnicotinicacidorfibricacidforelevatedtriglyceridesorlowHDLcholesterol4.ACEinhibitorinpatientswithCADorothervasculardisease,PharmacotherapyforChronicStableAngina,IIb(weaksupportiveevidence)Low-intensityanticoagulationwithwarfarininadditiontoaspirinBIII(notindicated)1.DipyridamoleB2.ChelationtherapyB,CURE,Approachtothetreatmentofchestpain,OXYGENDEMAND,Doubleproduct=(HeartRate)(systolicbloodpressure),BETABLOCKERS,Effectsof-blockadeonischemicheart,Printedfrom:DrugsfortheHeart2007Elsevier,Cardiaceffectsof-adrenergicblockingdrugsatthelevelsoftheSAnode,AVnode,conductionsystem,andmyocardium,Printedfrom:DrugsfortheHeart2007Elsevier,Contraindicationsto-blockade,Printedfrom:DrugsfortheHeart2007Elsevier,BETABLOCKERSSTUDIES,TIBET(TotalIschemicBurdenEuropeanTrial)APSIS(TheAnginaPrognosisStudyInStockholm)ASIST(AtenololSilentIschemiaTrial)TIBBS(TotalIschemicBurdenBisoprololStudy)IMAGE(InternationalMulticenterAnginaExerciseStudy),BBforclinicaluse,ACC/AHA2002GuidelineUpdatefortheManagementofPatientsWithChronicStableAngina,Comparisonofhemodynamiceffectsof-blockersandofCCBs,Printedfrom:DrugsfortheHeart2007Elsevier,CARDIACVS.VASCULAR,Printedfrom:DrugsfortheHeart2007Elsevier,Mechanismsofanti-ischemiceffectsofcalciumchannelblockers,Printedfrom:DrugsfortheHeart2007Elsevier,Verapamilanddiltiazemhaveabroadspectrumoftherapeuticeffects.,Printedfrom:DrugsfortheHeart2007Elsevier,Contraindicationstoverapamilordiltiazem,Printedfrom:DrugsfortheHeart2007Elsevier,Contraindicationstodihydropyridines,Printedfrom:DrugsfortheHeart2007Elsevier,PropertiesofCCBinclinicaluse,Schematicdiagramofeffectsofnitrateonthecirculation,Printedfrom:DrugsfortheHeart2007Elsevier,EffectsofnitratesingeneratingNOandstimulatingguanylatecyclasetocausevasodilation,Printedfrom:DrugsfortheHeart2007Elsevier,Currentproposalsfortherapyofnitratetolerance.,Printedfrom:DrugsfortheHeart2007Elsevier,Aseriousnitratedruginteraction,Printedfrom:DrugsfortheHeart2007Elsevier,NitratesinAngina,Effectofsimvastatinoncardiovasculareventsamongpatientswithandwithoutcoronaryheartdisease(CHD)intheHeartProtectionStudy,DualroleofACEinhibitors,bothpreventingandtreatingcardiovasculardisease,Printedfrom:DrugsfortheHeart2007Elsevier,Post-infarctionremodeling,Printedfrom:DrugsfortheHeart2007Elsevier,ACC/AHAGuidelinesforTreatmentofRiskFactors(classI),1.TreatmentofhypertensionaccordingtoJointNationalConferenceVIguidelinesA2.SmokingcessationtherapyB3.ManagementofdiabetesC4.Comprehensivecardiacrehabilitationprogram(includingexercise)B5.LDL-loweringtherapyinpatientswithdocumentedorsuspectedCADandLDLcholesterol130mg/dl,withatargetLDLof100mg/dlA6.Weightreductioninobesepatientsinthepresenceofhypertension,hyperlipidemia,ordiabetesmellitusC,ACC/AHAGuidelinesforTreatmentofRiskFactors(classIIa),1.InpatientswithdocumentedorsuspectedCADandLDLcholesterol100129mg/dl,severaltherapeuticoptionsareavailable:Ba.Lifestyleand/ordrugtherapiestolowerLDLto200mg/dl,withatargetnon-HDLcholesterol130mg/dlB3.Weightreductioninobesepatientsintheabsenceofhypertension,hyperlipidemia,ordiabetesmellitusC,ACC/AHAGuidelinesforTreatmentofRiskFactors(classIIb),1.FolatetherapyinpatientswithelevatedhomocysteinelevelsC2.IdentificationandappropriatetreatmentofclinicaldepressiontoimproveCADoutcomesC3.InterventiondirectedatpsychosocialstressreductionC,ACC/AHAGuidelinesforTreatmentofRiskFactors(classIII),1.InitiationofhormonereplacementtherapyinpostmenopausalwomenforthepurposeofreducingcardiovascularriskA2.VitaminsCandEsupplementationA3.ChelationtherapyC4.GarlicC5.AcupunctureC6.CoenzymeQC,SpecificGoalsforRiskReductionStrategiesinPatientswithChronicStableAngina,SmokingCompletecessationBloodpressure140/90or130/85mmHgifheartfailureorrenalinsufficiency;130/85mmHgifdiabetesLipidmanagementPrimarygoal:LDL100mg/dlSecondarygoal:Iftriglycerides200mg/dl,thennon-HDLshouldbe130mg/dlPhysicalactivityMinimumgoal:30min3or4d/wOptimalgoal:dailyWeightmanagementBMI18.524.9kg/m2DiabetesmanagementHbA1c7%,SpecificGoalsforRiskReductionStrategiesinPatientswithChronicStableAngina,Antiplateletagents/anticoagulants:Allpatients:indefiniteuseofaspirin75325mgperdayifnotcontraindicated.Considerclopidogrelasanalternativeifaspiriniscontraindicated.Managewarfarintointernationalnormalizedratio=2.0to3.0inpatientsaftermyocardialinfarctionwhenclinicallyindicatedorforthosenotabletotakeaspirinorclopidogrelACEinhibitors:Treatallpatientsindefinitelyaftermyocardialinfarction;startearlyinstablehigh-riskpatients(anteriormyocardialinfarction,previousmyocardialinfarction,KillipclassIIS3gallop,rales,radiographicCHF).Considerchronictherapyforallotherpatientswithcoronaryorothervasculardiseaseunlesscontraindicated.UseasneededtomanagebloodpressureorsymptomsinallotherpatientsBetablockers:Startinallpost-myocardialinfarctionandacutepatients(arrhythmia,LVdysfunction,inducibleischemia)at528days.Continue6mominimum.Observeusualcontraindications.Useasneededtomanageangina,rhythm,orbloodpressureinallpatients,ACC/AHAGuidelinesforEchocardiography,TreadmillExerciseTesting,StressRadionuclideImaging,StressEchocardiographyStudies,andCoronaryAngiographyDuringPatientFollow-Up,1.ChestradiographforpatientswithevidenceofneworworseningCHFC2.AssessmentofLVejectionfractionandsegmentalwallmotionbyechocardiographyorradionuclideimaginginpatientswithneworworseningCHForevidenceofinterveningmyocardialinfarctionbyhistoryorECGC3.EchocardiographyforevidenceofneworworseningvalvularheartdiseaseC4.Treadmillexercisetestforpatientswithoutpriorrevascularizationwhohaveasignificantchangeinclinicalstatus,areabletoexercise,anddonothaveanyoftheECGabnormalitieslistedinNo.5,ACC/AHAGuidelinesforEchocardiography,TreadmillExerciseTesting,StressRadionuclideImaging,StressEchocardiographyStudies,andCoronaryAngiographyDuringPatientFollow-Up,5.StressradionuclideimagingorstressechocardiographyproceduresforpatientswithoutpriorrevascularizationwhohaveasignificantchangeinclinicalstatusandareunabletoexerciseorhaveoneofthefollowingECGabnormalities:Ca.Preexcitation(Wolff-Parkinson-White)syndromeb.Electronicallypacedventricularrhythmc.Morethan1mmofrestSTdepressiond.Completeleftbundlebranchblock6.Stressradionuclideimagingorstressechocardiographyproceduresforpatientswhohaveasignificantchangeinclinicalstatusandrequiredastressimagingprocedureontheirinitialevaluationbecauseofequivocalorintermediate-risktreadmillresultsC7.StressradionuclideimagingorstressechocardiographyproceduresforpatientswithpriorrevascularizationwhohaveasignificantchangeinclinicalstatusC8.Coronaryangiographyinpatientswithmarkedlimitationofordinaryactivity(CCSclassIII)despitemaximalmedicaltherapy,Chronicstableangina,NEWTHERAPIES,Myocardialischemia:Sitesofactionofanti-ischemiamedication,(Stone,2004),Consequencesassociatedwithdysfunctionoflatesodiumcurrent,Diseases(eg,ischemia,heartfailure)Pathologicalmilieu(reactiveO2species,ischemicmetabolites)Toxinsanddrugs(eg,ATX-II,etc.),Na+channel(Gatingmechanismmalfunction),Diastolicrelaxationfailureincreasesoxygenconsumptionandreducesoxygensupply,Increasedmyocardialtensionduringdiastole:IncreasesmyocardialO2consumptionCompressesintramuralsmallvesselsReducesmyocardialbloodflowWorsensischemiaandangina,Ranolazine:Mechanismofaction,Ischemia,LateINa,Na+overload,Diastolicrelaxationfailure(increaseddiastolictension)Extravascularcompression,Ca2+overload,Monotherapywithranolazineincreasesexerciseperformanceattroughandpeak:MARISA,n=175,*p0.01vsplacebo;*p0.001vs.placebo,Peak,Trough,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,Placebo,500mgbid,1500mgbid,ChaitmanetalJACC2004;43:1375,Changefrombaseline,sec,n=791*p0.05;*p0.01;*p0.001vsplacebo.,Peak,Trough,*,*,*,*,*,*,*,*,*,Placebo,750mgbid,1000mgbid,*,Combinationregimenofranolazinewith:Atenolol50mgqd,orDiltiazem120mgqd,orAmlodipine5mgqd,(CARISA),Chaitmanetal.JAMA2004;291:309,Effectofranolazineinpatientswithrefractoryanginadespitemaximumamlodipinetherapy:ERICA,0,1,2,3,4,5,6,Amlodipine,+,Placebo,Amlodipine,+,Ranolazine,p=0.028,Baseline,Onplacebo,Onranolazine,Amlodipine,+,Placebo,Amlodipine,+,Ranolazine,p=0.014,p=0.18,0.0,1.0,2.0,3.0,4.0,5.0,5.5,0.5,1.5,2.5,3.5,4.5,Stoneetal.Circulation2005;112:II-748,Anginaepisodes/week,Numberofanginaepisodes/week,NTGconsumption/week,p=0.48,NumberofNTGsconsumed/week,TMR,Surgicalsurgeonsusethelasertomakebetween20and40tiny(one-millimeter-wide),PercutaneousTMR,Percutaneous,Rationale,improvedperfusionbystimulationofangiogenesispotentialplaceboeffectanestheticeffectmediatedbythedestructionofsympatheticnervescarryingpain-sensitiveafferentfibersPeri-proceduralinfarction.,EECP,EECP,Increasesarterialbloodpressureandretrogradeaorticbloodflowduringdiastole(diastolicaugmentation).Cuffsarewrappedaroundthepatientslegsandsequentialpressure(300mmHg)isappliedinearlydiastole.,Patientselection,AnginaclassIII/IVRefractorytomedicaltherapyReversibleischemiaofthefreewallnotamenableforrevas