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

USchoolofMedicinePresident,EasternChapter,AmericanSocietyofHypertensionFromclinicaltrialstoJNC7:EvidenceThatWillC

hangePracticeRecentClinicalTrialsin“UncomplicatedHypertension”thatInformJNC7HOT-Hanssonetal.,Lancet1998:351:1755–OptimalBP<140/90mm

Hg–FelodipinebasedtrialHOTStudy:RiskofaMajorCVEventReducedby30%(DBP)-30-25-20-15-10-5010095908085AchievedDBP(mmHg)OptimalDBPreductionHanss

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

CVEventReducedby30%(DBP)-25-20-15-10-50170160150130140AchievedSBP(mmHg)HanssonLetal.Lancet.1998;351:1755-1762*Fat

alandnonfatalMI,stroke,allotherCVdeaths.PercentriskreductioninmajorCVevents*OptimalSBPreductionHOTStudyResults:LowerisMarginallyBetterforNon-Diabetic

HypertensivesandASAisGoodThoseassignedto<80mmHggrouphadfewmyocardialinfarctionsthanthoseassignedto<90

mmHggroup2.6vs.3.6eventsper1000patientyears(p=0.05)ASAgroup(one-halfofthepatients)had15%fewCVevents(p=0.05)Ha

nssonetal.,Lancet1998:351:1755RecentClinicalTrialsin“UncomplicatedHypertension”STOP-2-Hanssonetal.,Lan

cet,1999;354:1751–56–Compared“old”(diureticsand-blockers)vs.“new”(calciumchannelblockersandACEinhibitors)inoverall

CVoutcomes–AllhadequalabilitytopreventCVmorbidityormortalityinelderlypatientswithhypertension.–ACEinhibito

rspreventedmoreMIandCHFthanCCBsINSIGHT-Brownetal.,Lancet,2000;356:366-72–Nifedipine-GITSvsdiuretic-basedtherapy.–E

quallyeffectiveinreducingstrokeandtotalcardiovascularevents,–GreaterincidenceofMIandCHFinCCBgroup.RecentCli

nicalTrialsin“UncomplicatedHypertension”NORDIL-Hanssonetal.,Lancet,2000;356:359-65–Diltiazemaseffectiveasdiureticand-blockertherapyinpr

eventingthecombinedprimaryendpointofallstroke,myocardialinfarction,andothercardiovasculardeath–CCBwasmoreeffectiveinreducingstroke.2ndAu

stralianNationalBPStudy,NEJM,2003;348:583-592–Lowriskelderlypopulation–ACEbetterthandiureticSummary:–BPre

ductioninthepatientwithuncomplicatedhypertensionisthecriticalfactor–Whichdrugisbettermaybeanuance–CCBmonotherapyappearstoberelatedtomore

CHF–CombinationsareusuallyrequiredRecentClinicalTrialsin“Complicated”HypertensionthatInformJNC7HOT-Hanssonetal.,Lancet

1998:351:1755HOPE-NEJM,2000;342:145-153;Lancet2000;355:253-259ALLHAT-JAMA2000Apr19;283(15):1967-75RENAAL-BrennerBM,etal.NEnglJMed.2

001;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-aldosteronesystemisbeneficial–Ifmultipleriskfa

ctors,includingdiabetes,bloodpressureloweringmaybemostimportant,diureticsshouldbepartoftherapyifpossibleHOTStudyResults:LowerisDefinitelyBetterinPa

tientswithDiabetesandHypertension50%reductioninmajorCVeventsinthosediabetichypertensivesassignedto<80mmHgcomparedto<90mmHggroupImpr

essive,sinceonly4mmHgdifferencebetweengroupsatendofstudyHanssonetal.,Lancet1998:351:1755ImpactofRandomize

dDrugClassonOutcomesinAASKAASKStudyGroup,JAMA.2002;288:2421-2431Follow-upBPbyDrugGroup(MeanSD)RamiprilAmlodipineMetopr

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

ts*Significantdifferencebetweenamlodipineandmetoprololgroups(p<0.05)AASKStudyGroup,JAMA.2002;288:2421-2431Mai

nClinicalCompositeOutcomeDecliningGFREvent,ESRD,orDeath%withEventsMetoprololvs.Amlodipine:RR=20%,p=0.17Ramiprilv

s.Amlodipine:RR=38%,p=0.004MetoprololRamiprilAmlodipine0510152025303540Follow-upMonth06121824303642485460Ramiprilvs.Metoprol

olRR=22%,p=0.042RR=RiskReduction,AdjustingforBaselineCovariatesAASKStudyGroup,JAMA.2002;288:2421-2431HardClinicalEndpointCompositeOfE

SRDorDeathFollow-upMonthMetoprololvs.Amlodipine:RR=42%,p=0.003Ramiprilvs.Amlodipine:RR=49%,p<0.001Ramiprilvs.Metoprolol:RR=21%,p

=0.11AmlodipineRamiprilMetoprolol%withEvents051015202530354006121824303642485460RR=RiskReduction,AdjustingforBaselineCovariatesAASKStudyGroup,JAMA.20

02;288:2421-2431%ofPatientsReachedUrineProtein>300mg/24hrsDuringFollow-upbyDrugGroupRamiprilvs.Metoprolol:p=0.014A

mlodipinevs.Metoprolol:p=0.009Ramiprilvs.Amlodipine:p<0.001%withEvents0102030405060Follow-upMonth06121824303642485460Analysisofpati

entswithUP/Cr<0.22atbaselineMetoprololRamiprilAmlodipineAASKStudyGroup,JAMA.2002;288:2421-2431ALLHAT:ChlorthalidoneGrouphadLowestAverageSystol

icBPALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.1501451401351300123456Follow-upYearsBloodPressuremmHgLisinoprilAmlodipineChlorthal

idoneBPvsChlorthalidoneat5Years+2mmHgP<.001+0.8mmHgP=.03MedicationUseandBPControlinALLHATCushmaneta

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

t:CHDDeathandNonfatalMIALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.RelativeRisk(95%CI)FavorsChlo

rthalidoneAmlodipine0.98(0.90-1.07)0.71.3Lisinopril0.99(0.91-1.08)FavorsAmlodipineFavorsLisinopril1ALLHAT:SecondaryEndpoints:StrokeRelativeRis

k(95%CI)FavorsAmlodipineFavorsLisinopril0.93(0.82-1.06)1.15(1.02-1.30)FavorsChlorthalidoneAmlodipineLisinopril0.511.5ALLHAT:Stroke(LisinoprilvsChlor

thalidone)SubgroupsLisinoprilBetterChlorthalidoneBetter0.512TotalAge<65Age65MenWomenBlackNonblackDiabeticNondiabetic

1.15(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)1.00(0.85-1.17)1.07(0.90-1.28)1.23(1.05-1.44)R

elativeRisk(95%CI)ALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.ALLHAT:SecondaryEndpoints:CombinedCVDRelativeRisk

(95%CI)1.04(0.99-1.09)1.10(1.05-1.16)AmlodipineLisinopril0.511.5FavorsAmlodipineFavorsChlorthalidoneALLHATCollabor

ativeResearchGroup.JAMA.2002;288:2981-2997.FavorsLisinoprilALLHAT:CombinedCVD(LisinoprilvsChlorthalidone)Subgroups1.5TotalAge<

65Age65MenWomenBlackNonblackDiabeticNondiabetic1.10(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)1.08(1.00-1.17)1.12(1.05-1.19)0.51LisinoprilBetterChlorthalidoneBetter

RelativeRisk(95%CI)ALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.ALLHAT:ComponentsofSecondaryEndpoin

ts*:HeartFailure*HeartfailureisacomponentofcombinedCVD.ALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.1.38(1.25-1.52)RelativeRisk

(95%CI)FavorsAmlodipineFavorsLisinoprilHeartFailure(fatal,nonfatal,hospitalizedortreated)1.19(1.07-1.31)Amlodi

pineLisinoprilHospitalized/FatalHF1.35(1.21-1.50)1.10(0.98-1.23)AmlodipineLisinoprilFavorsChlorthalidone0.52.01ALLHAT:HeartFailure(Am

lodipinevsChlorthalidone)Subgroups20.51AmlodipineBetterChlorthalidoneBetterTotalAge<65Age65MenWomenBlackNonblac

kDiabeticNondiabetic1.38(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)ALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.ALLHAT:HeartFailure(Lisino

prilvsChlorthalidone)SubgroupsTotalAge<65Age65MenWomenBlackNonblackDiabeticNondiabetic1.20(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)1.15(1.01-1.30)1.22(1.05-1.42)1.20(1.04-1.38)0.512LisinoprilBetterChlorthalidone

BetterRelativeRisk(95%CI)ALLHATCollaborativeResearchGroup.JAMA.2002;288:2981-2997.ALLHATSummaryandConclusionsTheALLHATtrial

addressedthemosttypicalpatient--i.e.the55y.o.withanotherriskfactorforCAD,manyofwhomhadpriorCVDItbringstherapeuticsbackto30yearsago,butwithatwist

--thechlorthalidonedosewas12.5mgcomparedtohigherdosesusedinthe1970sand1980s–Avoidsthediuretic-relatedhypokalemiaissuesofthe70sand80sP

atientstreatedwithdiureticshadlowerriskofstroke,heartfailureandCHDcomparedtopatientstakinglisinoprilALLHATColl

aborativeResearchGroup.JAMA.2002;288:2981-2997.U.S.DepartmentofHealthandHumanServicesNationalInstitutesofHealthNationalHeart,Lung,andBloo

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

214161820Riskofhypertension(%)Residualriskofdevelopinghypertensionamongpeoplewithbloodpressure<140/90mmHgatbaseline(Framingh

am)YearsLifetimeRiskofDevelopingHypertensionBeginningatAge65MenWomenVasanRS,etal.JAMA.2002;287:1003Depar

tmentofMedicine-LenoxHill-NYUSchoolofMedicineNewFeaturesandKeyMessages(Continued)▪▪▪▪NewFeaturesandKeyMessages(Continued)▪▪▪▪BP

MeasurementandClinicalEvaluation▪▪▪▪▪▪BloodPressureClassificationNormal<120and<80Prehypertension120–139or80–89Stage1Hypertension140–159or9

0–99Stage2Hypertension>160or>100BPClassificationSBPmmHgDBPmmHg*ClassificationofBP(JNC6)SystolicDiastolic129139159179120

-130-140-160->18080-8485-8990-99100-109>110Optimal<120/80DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineJNC6,Archiveso

fInternalMedicine1997;157:2413CVDRisk▪▪▪▪%ofMen%ofMen051015202530<110110-119120-129130-139140-149150-159160+051015202530<7070-7475-7980-8485-899

0-9495-99100+543210321.510.502.5AdjustedRelativeRiskAdjustedRelativeRiskSBP,mmHgDBP,mmHg*CVMortality–WhereAretheD

eaths?DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineNHBPEPWorkingGroupReport,1993BenefitsofLoweringBPBenefitsofLoweringBPBPContro

lRatesNationalHealthandNutritionExaminationSurvey,PercentII1976–80II(Phase1)1988–91II(Phase2)1991–941999–2000Awareness51736870Treat

ment31555459Control10292734BPMeasurementTechniquesMethodBriefDescription(morefollows)In-officeTworea

dings,5minutesapart,sittinginchair.Confirmelevatedreadingincontralateralarm.AmbulatoryBPmonitoringIndicatedforevaluationof“white-coat”HTN.Absence

of10–20%BPdecreaseduringsleepmayindicateincreasedCVDrisk.Self-measurementProvidesinformationonresponsetoth

erapy.Mayhelpimproveadherencetotherapyandevaluate“white-coat”HTN.AmbulatoryBPMonitoring▪▪▪▪Approximately25%ofHypertensiveshaveWCH26.37.3

0510152025306monthsfollow%PatientsNoMedicationABPMCBP=clinicBPStaessenetal.,JAMA1997;278:1065PatientswithWhite-CoatHypertensionHaveSa

meProbabilityofEventFreeSurvivalasNormotensivesby7.5YearsVerdecchiaPetal.Hypertension24:793-801,1994N=1187,meanage45±15yearsNml.DaytimeBP=<136/87fo

rmen<131/86forwomenNonSH=officeHTN,normalAPBMMiSH=officeHTN,daytimeSBP140-159mmHgMoSH=officeHTN,daytimeSBP160mmHgInTheSyst-EurStudy,ThosewithWCH

hadFewEventsandRxDidNotModifyRiskFagardetal,Circulation2000;102:1139-1144.40Stroke200CardiovascularEvents02040608

0EventRateper1000Patient-Years(NumberofEvents)(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=0.03MoSHPla

ceboTreatmentSelf-MeasurementofBP▪▪▪PatientEvaluationIdentifiableCausesofSecondaryHypertension▪▪▪▪▪▪▪▪▪LaboratoryTests▪▪▪TreatmentOverview▪▪

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

sAdoptDASHeatingplan8–14mmHgDietarysodiumreduction2–8mmHgPhysicalactivity4–9mmHgModerationofalcoholconsumption2–4mmHgEfficaciousLifestyleModific

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

ping“smart”EtOHto30cc=1oz/day➢whiskey3oz,wine10oz,beer24oz;halfinwomenExercise➢dynamicactivity45min

3-4times/wkSaltsdmnfabcSaltDASHDiet:EatingPlan*FoodgroupServingsServingsizesExamplesGrains&grain7-8daily1slicebreadWhole

wheatbread,Englishproductsdrycerealmuffins,pitabread,bagels,1/2Ccookedrice,cereals,grits,oatmealVegetables4-5daily1Craw,leafyTomatoes,p

otatoes,carrots,peas,squash,broccoli,leafy6oz.Vegetablegreenssweetpotatoes,beansjuiceFruits4-5daily6ozfruitjuiceApricots,bananas,dates,grapes1me

diumfruitoranges,grapefruit,mangoesmelons,peaches,pineapples,prunes,raisins,strawberries,Low-fatornonfat2-3daily8ozmilkSkimor1%milk,non

fatorlow1Cyogurtfatyogurt,nonfatorpart-skim1.5ozcheesecheeseMeats,poultry,2or3oz.cookedmeatLeanmeats;trimvisiblefat;fi

shpoultryorfishremoveskinfrompoultry;broilNuts,seeds,4-5per1.5oz.NutsAlmonds,filberts,mixednutslegumes2tbspseedspeanuts

,walnuts,sunflowerseedkidneybeans,lentils122124126128130132134SBP(mmHg)ControlFruits&VegetablesCombinat

ionDiet7880828486Baseline1234567and8InterventionWeekDBP(mmHg)AppelLJ,etal.,NEJM1997;336:1117-1124DASHStudy:8weekFruitand

VegetableRichDiet(4-5servingseach),Low-fatDairyFoods,andReducedTotalandSaturatedFat,(CombinationDiet)LowersBP

inNormotensivesandStageIHypertensivesDASHDietHasSignificantEffectonSystolicBPinPatientwithISHSystolicBP(mmHg

)132134136138140142144146148BaselineSBPPost-DietSBPControlDietFruit/VegetableDietDASHDiet-0.6mmHg-3.8mmHg-11.8m

mHg*p<0.001Mooreetal.,Hypertension,2001;38:155-158AlgorithmforTreatmentofHypertensionNotatGoalBloodP

ressure(<140/90mmHg)(<130/80mmHgforthosewithdiabetesorchronickidneydisease)InitialDrugChoicesDrug(s)forthecompellingindica

tionsOtherantihypertensivedrugs(diuretics,ACEI,ARB,BB,CCB)asneeded.WithCompellingIndicationsLifestyleModificationsS

tage2Hypertension(SBP>160orDBP>100mmHg)2-drugcombinationformost(usuallythiazide-typediureticandACEI,orARB,orBB,orCCB)Stage

1Hypertension(SBP140–159orDBP90–99mmHg)Thiazide-typediureticsformost.MayconsiderACEI,ARB,BB,CCB,orcombination.WithoutCompellingIndicationsNota

tGoalBloodPressureOptimizedosagesoraddadditionaldrugsuntilgoalbloodpressureisachieved.Considerconsultationwithhypertensionspecialist.CompellingIndi

cationsforIndividualDrugClassesCompellingIndicationInitialTherapyOptionsClinicalTrialBasisACC/AHAHeartFailureGuideline,MERIT-HF,COPE

RNICUS,CIBIS,SOLVD,AIRE,TRACE,ValHEFT,RALESACC/AHAPost-MIGuideline,BHAT,SAVECapricorn,EPHESUSALLHAT,HO

PE,ANBP2,LIFE,CONVINCETHIAZ,BB,ACEI,ARB,ALDOANTBB,ACEI,ALDOANTTHIAZ,BB,ACE,CCBHeartfailurePostmyocardialinfarctionHighCADriskDiabetesChronickidn

eydiseaseRecurrentstrokepreventionCompellingIndicationsforIndividualDrugClassesCompellingIndicationInitialTherapyOptionsClini

calTrialBasisNKF-ADAGuideline,UKPDS,ALLHATNKFGuideline,CaptoprilTrial,RENAAL,IDNT,REIN,AASKPROGRESSTHIAZ,B

B,ACE,ARB,CCBACEI,ARBTHIAZ+ACEIClassificationandManagementofBPforadultsBPclassificationSBP*mmHgDBP*mmHgLifestylemodificationInitialdrugtherapy

WithoutcompellingindicationWithcompellingindicationsNormal<120and<80EncouragePrehypertension120–139or80–89YesNoantihypertensivedrugindicated

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

orcombination.Drug(s)forthecompellingindications.‡Otherantihypertensivedrugs(diuretics,ACEI,ARB,BB,CCB)asneeded.Stage2Hypertension>1

60or>100YesTwo-drugcombinationformost†(usuallythiazide-typediureticandACEIorARBorBBorCCB).*TreatmentdeterminedbyhighestBPcate

gory.†Initialcombinedtherapyshouldbeusedcautiouslyinthoseatriskfororthostatichypotension.‡Treatpatientswithchro

nickidneydiseaseordiabetestoBPgoalof<130/80mmHg.UKPDS=UnitedKingdomProspectiveDiabetesStudy;MDRD=ModificationofDietinRenalDisease;HOT=Hy

pertensionOptimalTreatment;AASK=AfricanAmericanStudyofKidneyDisease;RENAAL=ReductionofEndpointsinNIDDMwiththeAngiotensinIIAntag

onistLosartan;IDNT=IrbesartanDiabeticNephropathyTrial.HypertensioninHigh-RiskPatients:NumberofAgentsNeededN

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

DepartmentofMedicine-LenoxHill-NYUSchoolofMedicineavgMinorityPopulations▪▪▪▪▪EffectofDifferentAntihypertensivesonBPof*HispanicSubj

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

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

choolofMedicineLafferandElijovich,JClinHypertens2002;4:266AdditionalConsiderationsinAntihypertensiveDrugChoices▪▪▪▪AdditionalConsiderationsinAnt

ihypertensiveDrugChoices▪▪▪▪▪