基于临床试验高血压治疗策略.ppt

HypertensionTreatmentStrategyBasedonClinicalTrialsLiuLisheng,Isantihypertensivetreatmentbeneficial?Trialsofactivetreatmentvs.placebo(ormorevs.less)Whenshoulddrugtreatmentstart?(BPlevel?Mildhypertension?Riskstratifications?)Whomshouldbetreated?(Severe,mild,ISH)Towhatextent?IsBPloweringbydifferentantihypertensiveagentsequallybeneficial?NecessityofConductingLarge-scaleClinicalStudiesusingAsianSubjects,Isantihypertensivetreatmentbeneficial?Trialsofactivetreatmentvs.placebo(ormorevs.less)Whenshoulddrugtreatmentstart?(BPlevel?Mildhypertension?Riskstratifications?)Whomshouldbetreated?(Severe,mild,ISH)Towhatextent?IsBPloweringbydifferentantihypertensiveagentsequallybeneficial?NecessityofConductingLarge-scaleClinicalStudiesusingAsianSubjects,Isolatedsystolichypertension,(%),(%),Stroke,CHD,Allcause,CV,NonCV,Fatalandnon-fatalevents,Mortality,Systolic-diastolichypertension,Stroke,CHD,Allcause,CV,NonCV,Fatalandnon-fatalevents,Mortality,EventReductioninPatientsonActiveAntihypertensiveTreatmentversusPlaceboorNoTreatment,ESH-ESCHypertensionGuidelines.JHypertens.2003.,0.01,0.01,0.001,NS,0.001,0.001,0.02,0.01,NS,0.001,BloodPressureLoweringTreatmentTrialistsCollaborationEffectsofDifferentBlood-Pressure-LoweringRegimensonMajorCardiovascularEvents:,BPLTTrialistsCollaboration.Lancet.2003;362:152735.,ResultsofProspectivelyDesignedOverviewsofRandomizedTrial,Meta-AnalysisofAntihypertensiveTreatmentTrials:EffectsonMajorCardiovascularEvents,BPLTTrialistsCollaboration.Lancet.2003;362:152735.,Placebo-controlledstudiesACEIvsplaceboCAvsplaceboMorevslessActivevsactiveregimenstudiesACEIvsD/BBCAvsD/BBACEIvsCA,Trials534695,Relativerisk0.78(0.730.83)0.82(0.710.95)0.85(0.760.95)1.02(0.981.07)1.04(1.001.09)0.97(0.921.03),0.5,1.0,2.0,Favours2ndlisted,Favours1stlisted,Relativerisk,BPdifference5/28/44/3+2/0+1/0+1/+1,Meta-AnalysisofAntihypertensiveTreatmentTrials:EffectsonStroke,BPLTTrialistsCollaboration.Lancet.2003;362:152735.,Placebo-controlledstudiesACEIvsplaceboCAvsplaceboMorevslessActivevsactiveregimenstudiesACEIvsD/BBCAvsD/BBACEIvsCA,Trials544595,BPdifference5/28/44/3+2/0+1/0+1/+1,Relativerisk0.72(0.640.81)0.62(0.470.82)0.77(0.630.95)1.09(1.001.18)0.93(0.861.00)1.12(1.011.25),0.5,1.0,2.0,Favours2ndlisted,Favours1stlisted,Relativerisk,Meta-AnalysisofAntihypertensiveTreatmentTrials:EffectsonCHDEvents,BPLTTrialistsCollaboration.Lancet.2003;362:152735.,Placebo-controlledstudiesACEIvsplaceboCAvsplaceboMorevslessActivevsactiveregimenstudiesACEIvsD/BBCAvsD/BBACEIvsCA,Trials544595,Relativerisk0.80(0.730.88)0.78(0.620.99)0.95(0.811.11)0.98(0.911.05)1.01(0.941.08)0.96(0.881.04),0.5,1.0,2.0,Favours2ndlisted,Favours1stlisted,Relativerisk,BPdifference5/28/44/3+2/0+1/0+1/+1,Meta-AnalysisofAntihypertensiveTreatmentTrials:EffectsonHeartFailure,BPLTTrialistsCollaboration.Lancet.2003;362:152735.,Placebo-controlledstudiesACEIvsplaceboCAvsplaceboMorevslessActivevsactiveregimenstudiesACEIvsD/BBCAvsD/BBACEIvsCA,Trials534374,Relativerisk0.82(0.690.98)1.21(0.931.58)0.84(0.591.18)1.07(0.961.19)1.33(1.211.47)0.82(0.730.92),0.5,1.0,2.0,Favours2ndlisted,Favours1stlisted,Relativerisk,BPdifference5/28/44/3+2/0+1/0+1/+1,ComparisonsofARB-BasedRegimensWithControlRegimens,BPLTTrialistsCollaboration.Lancet.2003;362:152735.,0.5,1.0,2.0,FavoursControl,FavoursARB,Relativerisk,StrokeCHDHeartfailureMajorCVeventsCVdeathTotalmortality,Trials443444,Relativerisk(95%CI)0.79(0.690.90)0.96(0.851.09)0.84(0.720.97)0.90(0.830.96)0.96(0.851.08)0.94(0.861.02),396/8412435/8412302/59351135/8412491/8412887/8412,500/8379450/8379359/59191268/8379511/8379943/8379,Diff.inBP(mean,mmHg)2/12/12/12/12/12/1,P0.460.430.260.780.340.59,Events/Participants,TrialsComparingDifferentAntihypertensiveRegimens:NewOnsetDiabetes,Zanchetti,Ruilope.JHypertens.2002;20:2099110.,TrialSHEPHOPENORDILSTOP-2INSIGHTNICS-EHCAPPPSTOP-2STOP-2LIFESCOPEALLHATALLHATINVEST,ComparisonDvsPACEvsPCAvsD/BCAvsD/BCAvsDCAvsDACEIvsD/BACEIvsD/BACEIvsCAAIIAvsBAIIAvsusualDvsCADvsACEICAvsB,Years34.54.553.556.1554.83.7442.7,18.63.6-4.30-64.311.611.66.9,PNS0.001NSNS0.05NS0.039NSNS0.0010.090.040.001,Treatment,27.55.4-5.61.9-85.39.89.17.9,-9.49.9-9.69.613.0,2-10.810.0-10.09.917.4,RR(95%CI)-0.66(0.510.85)0.87(0.731.04)0.97(0.731.29)-0.86(0.740.99)0.96(0.721.27)0.98(0.741.31)0.75(0.630.88)-0.87(0.780.97),%patient,n/1000ptyr,New-onsetdiabetes,1,LimitationsofEvent-BasedTrials,Trialsareofrelativelyshortduration(3-5years)andcoverasmallproportionofthelifeexpectancyofmiddle-ageduncomplicatedhypertensives.Mosttrialshaverecruitedcomplicatedhypertensivesonly.Aretheresultsofthesetrialsapplicabletoyoungeruncomplicatedhypertensives?Intermediateendpoints(subclinicaltargetorgandamage)mayprovideabetterindicationoflong-termdifferencesbetweentheeffectsofantihypertensiveagents.,Zanchetti2004,Event-BasedVersusTOD-BasedTrials,WhentrialsincludehypertensiveswithadvancedorgandamageandathighriskofearlyCVevents,intensiveBPloweringcaneffectivelypreventanumberofevents,butitislikelytobeunabletoinfluenceorgandamage,andtheancillarypropertiesofdifferentantihypertensiveagentsmayremainmasked.Inlessadvanceddiseaseandwhentheriskofeventsisloweranddelayed,thedifferentabilityofdifferentagentstoinfluenceorgandamageprogressionmaybetranslatedintodifferencesinlong-termbenefits.,Zanchetti2004,ChoiceofAntihypertensiveDrugs,DifferencesinsomeeffectorinsomegroupofpatientsmayexistARAmoreeffectivethanBorusualtherapyforstrokeinLVHorelderlyDiuretics,aloneorincombination,particularlyeffectiveforCHFACEIandARAmoreeffectiveondiabeticandnondiabeticnephropathyARAmoreeffectivethanBinLVHCAmoreeffectivethanDandBoncarotidatherosclerosisACEImoreeffectivethanDoncarotidatherosclerosisDrugsarenotequalintermsofadversedisturbances,ConfirmationofpreviousWHO-ISHguidelines:themainbenefitsofantihypertensivetherapyareduetoloweringBPperse,ESH-ESCHypertensionguidelinesJHypertens2003,TrialsComparingDifferentActiveAntihypertensiveAgentsisDifficult,Because:Smallerrelativebenefitstobeexpected.Hence,largesamplesize,highriskpts.needtoberandomized.,Isantihypertensivetreatmentbeneficial?Trialsofactivetreatmentvs.placebo(ormorevs.less)Whenshoulddrugtreatmentstart?(BPlevel?Mildhypertension?Riskstratifications?)Whomshouldbetreated?(Severe,mild,ISH)Towhatextent?IsBPloweringbydifferentantihypertensiveagentsequallybeneficial?NecessityofConductingLarge-scaleClinicalStudiesusingAsianSubjects,Morbidity363.,VALUE:OtherResults,Incidenceofstrokewaslower,butnotsignificantly,intheamlodipinegroupIncidenceofnon-fatalMIwassignificantlylowerintheamlodipinegroupTherewasapositivetrendinfavourofvalsartanforlessheartfailurebutthisdidnotreachsignificanceTherewasahighlysignificantlowerrateofnew-onsetdiabetesinthevalsartangroup,JuliusSetal.Lancet.June2004;363.,TheobserveddifferenceinstrokeratesappearstobestronglyrelatedtodifferencesinachievedBPsThebenefitsofvalsartaninheartfailurepreventionemergedlaterinthestudywhenBPdifferencesweresmaller,indicatingthatthereisapotentialbeneficialeffectofvalsartanbeyondBPcontrol,VALUE:Interpretations,JuliusSetal.Lancet.June2004;363.,VALUE:Interpretations,VALUEisthefirsttrialtoshowalowerrateofnew-onsetdiabeteswhenanARB(valsartan)wascomparedtoaCCB(amlodipine)Long-termimplicationsandmechanismsofthisimportantfindingdeservefurtherinvestiga