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RobertA.Phillips,M.D.,Ph.D.,F.A.C.C.,F.A.H.A.ChairmanDepartmentofMedicineLenoxHillHospitalProfessorofMedici

neNYUSchoolofMedicinePresident,EasternChapter,AmericanSocietyofHypertensionFromclinicaltrialstoJNC7:EvidenceThatWillChange

PracticeRecentClinicalTrialsin“UncomplicatedHypertension”thatInformJNC7HOT-Hanssonetal.,Lancet1998:351:1755–OptimalBP<140/90mmHg–Felodipinebasedtria

lHOTStudy:RiskofaMajorCVEventReducedby30%(DBP)-30-25-20-15-10-5010095908085AchievedDBP(mmHg)OptimalDBPreductionHan

ssonLetal.Lancet.1998;351:1755-1762PercentriskreductioninmajorCVevents**FatalandnonfatalMI,stroke,allotherCVdeaths.HOTStudy:Ris

kofaMajorCVEventReducedby30%(DBP)-25-20-15-10-50170160150130140AchievedSBP(mmHg)HanssonLetal.Lancet.1998;351:1755-1762*FatalandnonfatalMI,

stroke,allotherCVdeaths.PercentriskreductioninmajorCVevents*OptimalSBPreductionHOTStudyResults:LowerisMarginallyBetterforNon-DiabeticHype

rtensivesandASAisGoodThoseassignedto<80mmHggrouphadfewmyocardialinfarctionsthanthoseassignedto<90mmHggroup2.6vs.3.6eventsper1000patientyears(p=

0.05)ASAgroup(one-halfofthepatients)had15%fewCVevents(p=0.05)Hanssonetal.,Lancet1998:351:1755RecentClinicalTrialsin“Uncompli

catedHypertension”STOP-2-Hanssonetal.,Lancet,1999;354:1751–56–Compared“old”(diureticsand-blockers)v

s.“new”(calciumchannelblockersandACEinhibitors)inoverallCVoutcomes–AllhadequalabilitytopreventCVmorbidityormortalityinelderlypatie

ntswithhypertension.–ACEinhibitorspreventedmoreMIandCHFthanCCBsINSIGHT-Brownetal.,Lancet,2000;356:366-72–Nifedipine-GITSvsdiuretic-basedther

apy.–Equallyeffectiveinreducingstrokeandtotalcardiovascularevents,–GreaterincidenceofMIandCHFinCCBgroup.RecentClinicalTrialsin“Uncomplica

tedHypertension”NORDIL-Hanssonetal.,Lancet,2000;356:359-65–Diltiazemaseffectiveasdiureticand-blockerth

erapyinpreventingthecombinedprimaryendpointofallstroke,myocardialinfarction,andothercardiovasculardeath–CCBwasmoreeffectivein

reducingstroke.2ndAustralianNationalBPStudy,NEJM,2003;348:583-592–Lowriskelderlypopulation–ACEbetterthandiureticSummary:–BPred

uctioninthepatientwithuncomplicatedhypertensionisthecriticalfactor–Whichdrugisbettermaybeanuance–CCBmonotherapya

ppearstoberelatedtomoreCHF–CombinationsareusuallyrequiredRecentClinicalTrialsin“Complicated”HypertensionthatInformJNC7HOT-Hanssonetal

.,Lancet1998:351:1755HOPE-NEJM,2000;342:145-153;Lancet2000;355:253-259ALLHAT-JAMA2000Apr19;283(15):1967-75RENAAL-Bren

nerBM,etal.NEnglJMed.2001;345:861-869.IDNT-LewisEJ,etal.NEnglJMed.2001;345:851-860.AASK–AASKStudyGroup,JAMA,2002;ALLHAT–2002

,JAMA,2002;288:2981-2997ClinicalSummary:–Inrenaldisease,blockadeoftherenin-angiotensin-aldosteronesys

temisbeneficial–Ifmultipleriskfactors,includingdiabetes,bloodpressureloweringmaybemostimportant,diureticsshouldbepart

oftherapyifpossibleHOTStudyResults:LowerisDefinitelyBetterinPatientswithDiabetesandHypertension50%reductioninmajorCVeventsinthosediabetichypertensive

sassignedto<80mmHgcomparedto<90mmHggroupImpressive,sinceonly4mmHgdifferencebetweengroupsatendofstudyHanssonetal.,Lancet1998:351:175

5ImpactofRandomizedDrugClassonOutcomesinAASKAASKStudyGroup,JAMA.2002;288:2421-2431Follow-upBPbyDrugGroup(MeanSD)RamiprilAmlodipineM

etoprololMAP(mmHg)10099981009SystolicBP(mmHg)1351413312*13513DiastolicBP(mmHg)829818819Summariesinc

ludevisitsafterthreemonthsandexcludeGFRvisits*Significantdifferencebetweenamlodipineandmetoprololgroups(p<0.05)AASK

StudyGroup,JAMA.2002;288:2421-2431MainClinicalCompositeOutcomeDecliningGFREvent,ESRD,orDeath%withEventsMetoprololvs.Amlodip

ine:RR=20%,p=0.17Ramiprilvs.Amlodipine:RR=38%,p=0.004MetoprololRamiprilAmlodipine0510152025303540Foll

ow-upMonth06121824303642485460Ramiprilvs.MetoprololRR=22%,p=0.042RR=RiskReduction,AdjustingforBaselineCovariatesAASKStudyGrou

p,JAMA.2002;288:2421-2431HardClinicalEndpointCompositeOfESRDorDeathFollow-upMonthMetoprololvs.Amlodipine:RR=42%,p=

0.003Ramiprilvs.Amlodipine:RR=49%,p<0.001Ramiprilvs.Metoprolol:RR=21%,p=0.11AmlodipineRamiprilMetoprolol%withEvents05

1015202530354006121824303642485460RR=RiskReduction,AdjustingforBaselineCovariatesAASKStudyGroup,JAMA.2002;288:2421-2431%of

PatientsReachedUrineProtein>300mg/24hrsDuringFollow-upbyDrugGroupRamiprilvs.Metoprolol:p=0.014Amlodipinevs.Metoprolol:p=0.009Ramipr

ilvs.Amlodipine:p<0.001%withEvents0102030405060Follow-upMonth06121824303642485460AnalysisofpatientswithUP/Cr<0.22atbaselineMetoprol

olRamiprilAmlodipineAASKStudyGroup,JAMA.2002;288:2421-2431ALLHAT:ChlorthalidoneGrouphadLowestAverageSystolicBPALLHATCollaborativeRese

archGroup.JAMA.2002;288:2981-2997.1501451401351300123456Follow-upYearsBloodPressuremmHgLisinoprilAmlodipineChl

orthalidoneBPvsChlorthalidoneat5Years+2mmHgP<.001+0.8mmHgP=.03MedicationUseandBPControlinALLHATCushma

netal.JClinHypertens.2002;4:393-404.020406080100Baseline6mo1y3y5y1Drug2Drugs3Drugs%Controlled<140/90mmHg%PatientsALLHAT

PrimaryEndpoint:CHDDeathandNonfatalMIALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.RelativeRisk(95%CI)FavorsChlorthalidoneAmlodipine0.98(0

.90-1.07)0.71.3Lisinopril0.99(0.91-1.08)FavorsAmlodipineFavorsLisinopril1ALLHAT:SecondaryEndpoints:S

trokeRelativeRisk(95%CI)FavorsAmlodipineFavorsLisinopril0.93(0.82-1.06)1.15(1.02-1.30)FavorsChlorthalidoneAmlodipineLisinopril0.511.5ALLHAT:Strok

e(LisinoprilvsChlorthalidone)SubgroupsLisinoprilBetterChlorthalidoneBetter0.512TotalAge<65Age65MenW

omenBlackNonblackDiabeticNondiabetic1.15(1.02-1.30)1.21(0.97-1.52)1.13(0.98-1.30)1.10(0.94-1.29)1.22(1.01-1.46)1.40(1.17-1.68)1.0

0(0.85-1.17)1.07(0.90-1.28)1.23(1.05-1.44)RelativeRisk(95%CI)ALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2

997.ALLHAT:SecondaryEndpoints:CombinedCVDRelativeRisk(95%CI)1.04(0.99-1.09)1.10(1.05-1.16)AmlodipineLis

inopril0.511.5FavorsAmlodipineFavorsChlorthalidoneALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.FavorsLisinoprilALLHAT:

CombinedCVD(LisinoprilvsChlorthalidone)Subgroups1.5TotalAge<65Age65MenWomenBlackNonblackDiabeticNondiabetic1.1

0(1.05-1.16)1.05(0.97-1.15)1.13(1.06-1.20)1.08(1.02-1.15)1.12(1.03-1.21)1.19(1.09-1.30)1.06(1.00-1.13)1.0

8(1.00-1.17)1.12(1.05-1.19)0.51LisinoprilBetterChlorthalidoneBetterRelativeRisk(95%CI)ALLHATCollaborativeR

esearchGroup.JAMA.2002;288:2981-2997.ALLHAT:ComponentsofSecondaryEndpoints*:HeartFailure*HeartfailureisacomponentofcombinedCVD.ALLHATCollaborativeRe

searchGroup.JAMA.2002;288:2981-2997.1.38(1.25-1.52)RelativeRisk(95%CI)FavorsAmlodipineFavorsLisinoprilH

eartFailure(fatal,nonfatal,hospitalizedortreated)1.19(1.07-1.31)AmlodipineLisinoprilHospitalized/FatalHF1.35(1.21-1.50)1.10(0.98-1.23)Amlod

ipineLisinoprilFavorsChlorthalidone0.52.01ALLHAT:HeartFailure(AmlodipinevsChlorthalidone)Subgroups20.51AmlodipineBetterChlor

thalidoneBetterTotalAge<65Age65MenWomenBlackNonblackDiabeticNondiabetic1.38(1.25-1.52)1.51(1.25-1.82)1.33(1.18-1.49)1.41(

1.24-1.61)1.33(1.14-1.55)1.47(1.24-1.74)1.33(1.18-1.51)1.42(1.23-1.64)1.33(1.16-1.52)RelativeRisk(95%CI)ALLHATCollaborativeRe

searchGroup.JAMA.2002;288:2981-2997.ALLHAT:HeartFailure(LisinoprilvsChlorthalidone)SubgroupsTotalAge<65Age65

MenWomenBlackNonblackDiabeticNondiabetic1.20(1.09-1.34)1.23(1.01-1.50)1.20(1.06-1.35)1.19(1.03-1.36)1.23(1.05-1.43)1.32(1.11-1.58)1.1

5(1.01-1.30)1.22(1.05-1.42)1.20(1.04-1.38)0.512LisinoprilBetterChlorthalidoneBetterRelativeRisk(95%CI)ALLHATCo

llaborativeResearchGroup.JAMA.2002;288:2981-2997.ALLHATSummaryandConclusionsTheALLHATtrialaddressedthemosttypicalpatie

nt--i.e.the55y.o.withanotherriskfactorforCAD,manyofwhomhadpriorCVDItbringstherapeuticsbackto30yearsago,butwithat

wist--thechlorthalidonedosewas12.5mgcomparedtohigherdosesusedinthe1970sand1980s–Avoidsthediuretic-relatedhypokalemiaissuesofthe70s

and80sPatientstreatedwithdiureticshadlowerriskofstroke,heartfailureandCHDcomparedtopatientstakinglisinoprilALLHATCollaborativeResearchGroup.JAMA.200

2;288:2981-2997.U.S.DepartmentofHealthandHumanServicesNationalInstitutesofHealthNationalHeart,Lung,andBloodIn

stituteTheSeventhReportoftheJointNationalCommitteeonPrevention,Detection,Evaluation,andTreatmentofHighBloodPressure(JNC7)▪▪▪▪02040608010002468101

214161820Riskofhypertension(%)Residualriskofdevelopinghypertensionamongpeoplewithbloodpressure<140/90mmHgatbas

eline(Framingham)YearsLifetimeRiskofDevelopingHypertensionBeginningatAge65MenWomenVasanRS,etal.JAMA.2002;287:1003

DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineNewFeaturesandKeyMessages(Continued)▪▪▪▪NewFeaturesandKeyMessages(Continued)

▪▪▪▪BPMeasurementandClinicalEvaluation▪▪▪▪▪▪BloodPressureClassificationNormal<120and<80Prehypertension120–139or8

0–89Stage1Hypertension140–159or90–99Stage2Hypertension>160or>100BPClassificationSBPmmHgDBPmmHg*Class

ificationofBP(JNC6)SystolicDiastolic129139159179120-130-140-160->18080-8485-8990-99100-109>110Optimal<120/80DepartmentofMedicine-LenoxHi

ll-NYUSchoolofMedicineJNC6,ArchivesofInternalMedicine1997;157:2413CVDRisk▪▪▪▪%ofMen%ofMen051015202530<110110-11912

0-129130-139140-149150-159160+051015202530<7070-7475-7980-8485-8990-9495-99100+543210321.510.502.5AdjustedRelativeRi

skAdjustedRelativeRiskSBP,mmHgDBP,mmHg*CVMortality–WhereAretheDeaths?DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineN

HBPEPWorkingGroupReport,1993BenefitsofLoweringBPBenefitsofLoweringBPBPControlRatesNationalHealthandN

utritionExaminationSurvey,PercentII1976–80II(Phase1)1988–91II(Phase2)1991–941999–2000Awareness517368

70Treatment31555459Control10292734BPMeasurementTechniquesMethodBriefDescription(morefollows)In-officeTworeadings,5minutesapart,sittingi

nchair.Confirmelevatedreadingincontralateralarm.AmbulatoryBPmonitoringIndicatedforevaluationof“white-coat”HTN.A

bsenceof10–20%BPdecreaseduringsleepmayindicateincreasedCVDrisk.Self-measurementProvidesinformationonresponsetotherapy.Mayhelpimproveadherencet

otherapyandevaluate“white-coat”HTN.AmbulatoryBPMonitoring▪▪▪▪Approximately25%ofHypertensiveshaveWCH26.37.30510152025306monthsfollow%PatientsNoMed

icationABPMCBP=clinicBPStaessenetal.,JAMA1997;278:1065PatientswithWhite-CoatHypertensionHaveSameProbabilityofEventFreeSurvivalasNormotens

ivesby7.5YearsVerdecchiaPetal.Hypertension24:793-801,1994N=1187,meanage45±15yearsNml.DaytimeBP=<136/87formen<131/86forwomenNonSH=officeHTN,normalAPB

MMiSH=officeHTN,daytimeSBP140-159mmHgMoSH=officeHTN,daytimeSBP160mmHgInTheSyst-EurStudy,ThosewithWCHhadFewEventsandRxDidNotModifyRiskFagardetal,Cir

culation2000;102:1139-1144.40Stroke200CardiovascularEvents020406080EventRateper1000Patient-Years(Numb

erofEvents)(6)(2)P=0.17(18)(16)P=0.32(25)(12)P=0.06(2)(0)P=0.16NonSH(6)(6)P=0.86MiSH(12)(3)P=0.03MoSHPlaceboTreatmentSelf-Measu

rementofBP▪▪▪PatientEvaluationIdentifiableCausesofSecondaryHypertension▪▪▪▪▪▪▪▪▪LaboratoryTests▪▪▪TreatmentOvervie

w▪▪▪GoalsofTherapy▪▪▪.LifestyleModificationModificationApproximateSBPreduction(range)Weightreduction5–20mmHg/10kgweightlossAdoptDAS

Heatingplan8–14mmHgDietarysodiumreduction2–8mmHgPhysicalactivity4–9mmHgModerationofalcoholconsumption2–4mmHgEfficaciousLifestyleM

odificationWeight:v1kg=1.6/1.3mmHg➢Achieve<15%aboveidealNaintake:v100mEq=5.4/6.5mmHg➢Achieve4-6gsalt/day(70-100mEqNa)➢Shopping“smart”

EtOHto30cc=1oz/day➢whiskey3oz,wine10oz,beer24oz;halfinwomenExercise➢dynamicactivity45min3-4times/wkSaltsdmnfabcSaltDASHDiet:EatingP

lan*FoodgroupServingsServingsizesExamplesGrains&grain7-8daily1slicebreadWholewheatbread,Englishproductsdrycerealmuffins,pitabre

ad,bagels,1/2Ccookedrice,cereals,grits,oatmealVegetables4-5daily1Craw,leafyTomatoes,potatoes,carrots,peas,squash,b

roccoli,leafy6oz.Vegetablegreenssweetpotatoes,beansjuiceFruits4-5daily6ozfruitjuiceApricots,bananas,dates,grapes1mediumfruitoranges,grap

efruit,mangoesmelons,peaches,pineapples,prunes,raisins,strawberries,Low-fatornonfat2-3daily8ozmilkSkimor

1%milk,nonfatorlow1Cyogurtfatyogurt,nonfatorpart-skim1.5ozcheesecheeseMeats,poultry,2or3oz.cookedmeatLeanmeats;trimvisiblefat;

fishpoultryorfishremoveskinfrompoultry;broilNuts,seeds,4-5per1.5oz.NutsAlmonds,filberts,mixednutslegumes2tbspseedspeanut

s,walnuts,sunflowerseedkidneybeans,lentils122124126128130132134SBP(mmHg)ControlFruits&VegetablesCombinationDiet7880828486Baseline123

4567and8InterventionWeekDBP(mmHg)AppelLJ,etal.,NEJM1997;336:1117-1124DASHStudy:8weekFruitandVegetableRichDiet(4-5servingseach),Low-fatDai

ryFoods,andReducedTotalandSaturatedFat,(CombinationDiet)LowersBPinNormotensivesandStageIHypertensivesDASHDietH

asSignificantEffectonSystolicBPinPatientwithISHSystolicBP(mmHg)132134136138140142144146148BaselineSBPPost-D

ietSBPControlDietFruit/VegetableDietDASHDiet-0.6mmHg-3.8mmHg-11.8mmHg*p<0.001Mooreetal.,Hypertension,2001;38:155-158A

lgorithmforTreatmentofHypertensionNotatGoalBloodPressure(<140/90mmHg)(<130/80mmHgforthosewithdiabetesorchronickidneydisease)I

nitialDrugChoicesDrug(s)forthecompellingindicationsOtherantihypertensivedrugs(diuretics,ACEI,ARB,BB,CCB)asneeded

.WithCompellingIndicationsLifestyleModificationsStage2Hypertension(SBP>160orDBP>100mmHg)2-drugcombinationformost(

usuallythiazide-typediureticandACEI,orARB,orBB,orCCB)Stage1Hypertension(SBP140–159orDBP90–99mmHg)Thiazide-typediuret

icsformost.MayconsiderACEI,ARB,BB,CCB,orcombination.WithoutCompellingIndicationsNotatGoalBloodPressureOptimizedo

sagesoraddadditionaldrugsuntilgoalbloodpressureisachieved.Considerconsultationwithhypertensionspecialist.CompellingIndicati

onsforIndividualDrugClassesCompellingIndicationInitialTherapyOptionsClinicalTrialBasisACC/AHAHeartFailureGuideline,MERIT-HF,COPERNICUS,CI

BIS,SOLVD,AIRE,TRACE,ValHEFT,RALESACC/AHAPost-MIGuideline,BHAT,SAVECapricorn,EPHESUSALLHAT,HOPE,ANBP2,LIFE,CONVINCETHIAZ,BB,ACEI,ARB,ALDOANTBB,ACE

I,ALDOANTTHIAZ,BB,ACE,CCBHeartfailurePostmyocardialinfarctionHighCADriskDiabetesChronickidneydiseaseRecurrentstrokepreventionCompellingIn

dicationsforIndividualDrugClassesCompellingIndicationInitialTherapyOptionsClinicalTrialBasisNKF-ADAGuideline,UKPDS,ALLHATN

KFGuideline,CaptoprilTrial,RENAAL,IDNT,REIN,AASKPROGRESSTHIAZ,BB,ACE,ARB,CCBACEI,ARBTHIAZ+ACEIClassifica

tionandManagementofBPforadultsBPclassificationSBP*mmHgDBP*mmHgLifestylemodificationInitialdrugtherapyWithoutcompellingindicationWithcompellingin

dicationsNormal<120and<80EncouragePrehypertension120–139or80–89YesNoantihypertensivedrugindicated.Drug(

s)forcompellingindications.‡Stage1Hypertension140–159or90–99YesThiazide-typediureticsformost.MayconsiderACEI,ARB,BB,CCB,orco

mbination.Drug(s)forthecompellingindications.‡Otherantihypertensivedrugs(diuretics,ACEI,ARB,BB,CCB)asneeded.Stage2Hypertension>160or>100YesTwo-drugco

mbinationformost†(usuallythiazide-typediureticandACEIorARBorBBorCCB).*TreatmentdeterminedbyhighestBPcate

gory.†Initialcombinedtherapyshouldbeusedcautiouslyinthoseatriskfororthostatichypotension.‡Treatpatientswithchronickidneydisea

seordiabetestoBPgoalof<130/80mmHg.UKPDS=UnitedKingdomProspectiveDiabetesStudy;MDRD=ModificationofDietinRenalDisease;H

OT=HypertensionOptimalTreatment;AASK=AfricanAmericanStudyofKidneyDisease;RENAAL=ReductionofEndpointsinNIDDMwiththe

AngiotensinIIAntagonistLosartan;IDNT=IrbesartanDiabeticNephropathyTrial.HypertensioninHigh-RiskPatients:NumberofAgentsNeed

edNumberofBPMedicationsUKPDS(<85mmHg,diastolic)4321MDRD(92mmHg,MAP)HOT(<80mmHg,diastolic)AASK(<92mmHg,MAP)RENAAL(<140/90mmHg)IDNT(<135/8

5mmHg)DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineavgMinorityPopulations▪▪▪▪▪EffectofDifferentAntihypertensivesonBPof*Hispani

cSubjects-40-30-20-10-20-10∆SystolicBP(mmHg)∆DiastolicBP(mmHg)**¥****¥*,¥:significantvsplaceboACEInh,n=24Blocker,n=1

3HCTZ+ACEInh,n=13HCTZ+Blocker,n=14Placebo,n=14Ca++Blocker,n=10HCTZ,n=18DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineLafferandElij

ovich,JClinHypertens2002;4:266AdditionalConsiderationsinAntihypertensiveDrugChoices▪▪▪▪AdditionalConsiderationsinAntihypertensiveDrug

Choices▪▪▪▪▪