02-坎地沙坦+氢氯噻嗪对比氯沙坦+氢氯噻嗪降压效果对比(英文)---副本

ComparisonoftheEfficacyandTolerabilityofCombinationTabletsContainingCandesartanCilexetilandHydrochlorothiazideorLosartanandHydrochlorothiazideinPatientswithModeratetoSevereHypertensionResultsoftheCARLOS-Study1WolfgangKoenig,onbehalfoftheMulticentreStudyGroupDepartmentofInternalMedicineII−Cardiology,UniversityofUlmMedicalCentre,Ulm,Germany1CAndesartan/HCTZveRsusLOSartan/HCTZ.AbstractObjectives:Tocomparethefixedcombinationsofcandesartancilexetilandhydrochlorothiazide(HCTZ)andlosartanandHCTZwithrespecttomagnitudeanddurationofantihypertensiveeffectandtolerability.DesignandSetting:Thiswasarandomised,double-blind,parallel-groupstudyconductedatninecentresinGermany.Patients:160patientswithmoderatetoseverehypertension,untreatedornotcontrolledonprevioustreatment,completedthestudy.Interventions:Patientswererandomisedto6weeksoftreatmentwithcande-sartancilexetilandHCTZ16/12.5mgoncedaily(n=81)orlosartanandHCTZ50/12.5mgoncedaily(n=79).Bloodpressuremeasurementswereperformedapproximately24and48hoursafterthelastdose.Results:Bothcandesartancilexetil/HCTZandlosartan/HCTZloweredbloodpressuresignificantlycomparedwithbaseline.Meanseatedbloodpressureswerereducedby32.2/21.1mmHg(systolic/diastolic)after6weeks,24hourspostdose,inthecandesartancilexetil/HCTZgroup.Correspondingreductionsinthelosartan/HCTZgroupwere23.8/14.9mmHg.Themeandifferencesinanti-hypertensiveeffectbetweentreatmentswere8.4/6.2mmHginfavourofcan-desartancilexetil(p0.001).Bloodpressurereductions48hourspostdosewere25.6/16.4mmHgforcandesartancilexetil/HCTZand9.2/4.2mmHgforlosartan/HCTZ,withdifferencesbetweentreatmentsbeinghighlysignificantinfavourofcandesartancilexetil/HCTZ(16.5/12.2mmHg;p0.001).Theproportionsofresponders(seateddiastolicbloodpressure≤90mmHgand/orareductionfrombaseline≥10mmHg)andcontrolledpatients(seateddiastolicbloodpressure≤90mmHg)oncandesartancilexetil/HCTZwere98and58%at24hours,and84and37%at48hourspostdose.Correspondingfiguresforlosartan/HCTZwere79and28%,and18and1.3%,respectively.AllCLINICALUSEClinDrugInvest2000Apr;19(4):239-2461173-2563/00/0004-0239/$20.00/0©AdisInternationalLimited.Allrightsreserved.differencesweresignificant(p0.001)infavourofcandesartancilexetil/HCTZ.Bothtreatmentswerewelltolerated.Conclusions:Candesartancilexetil/HCTZ16/12.5mgoncedailyreducedbloodpressuremoreeffectivelythanlosartan/HCTZ50/12.5mgoncedailyboth24and48hourspostdose.Thelong-lastingeffectofcandesartancilexetil/HCTZprovideseffectivebloodpressurecontrolevenafteramisseddose.Therenin-angiotensinsystemplaysanimpor-tantroleinthepathophysiologyofhypertension,andblockadeoftheangiotensinIItype1(AT1)receptorwithlosartan[1]andmorerecentlywithnewerdrugssuchascandesartan[2-4]hasbeendocumentedtoresultinconsiderablebloodpres-surereductions.Interveningwiththeeffectsofan-giotensinIIbydirectlyblockingtheAT1receptorratherthantheangiotensin-convertingenzyme(ACE)carriestheadvantageofanexcellenttoler-abilitycomparabletothatofplacebotreatment.[5]Apartfromaclear,lineardoseresponserelation-ship,[6]candesartandiffersfromlosartanthroughitsstrongerbindingwiththeAT1receptor[7,8]anditsslowdissociationfromthebindingsite,[9]lead-ingtogreaterantihypertensiveefficacy,[10-13]andaprolongeddurationofBPreduction.[14,15]ThecombinationofanAT1receptorantagonistsuchaslosartanorcandesartan,withalow-doseregimenofhydrochlorothiazide(HCTZ)inpatientsuncontrolledbymonotherapyisalogicalstepbasedonpathophysiologicalconsiderations.AT1receptorantagonistsaremosteffectiveinhypertensivepatientswithhighplasmareninactivity.[16]Inpatientswithlowplasmareninactivity,theadditionofadiureticwillstimulatetherenin-angiotensinsystemandhenceincreasetheefficacyoftheAT1receptorantagonist.FixedcombinationtabletsoflosartanandHCTZandofcandesartanandHCTZhavebeendevelopedandarepotentialalternativesforthemanagementofmoredifficult-to-treatormoreadvancedhyperten-sion.Therefore,theaimofthisstudywastocomparethemedium-termantihypertensiveefficacyandtolerabilityofthefixedcombinationofcandesartancilexetil/HCTZ16/12.5mgwiththecombinationoflosartan/HCTZ50/12.5mginpatientswithmoderatetoseverehypertension.PatientsandMethodsStudyDesignandPatientsThiswasarandomised,double-blind,parallelgrouptrialperformedinGermanyatninecentres.ThestudywasperformedinaccordancewiththedeclarationofHelsinkiandapprovedbytheEthicsCommitteeoftheUniversityofUlm.Writteninformedconsentwasobtainedfromallpatientsbeforeenrolmentafterinformationaboutthepurposeandmethodsofthestudyhadbeengiven.Eligiblepatients’bloodpressurewasmeasuredattwovisitsseparatedby1dayatminimumand7daysatmaximumwithoutanyformalplaceborun-in.Anypre-existingantihypertensivetreat-mentwaskeptunchanged.Ifseateddiastolicbloodpressure(DBP)was100mmHgand≤120mmHgateithermeasurementpatientswererandomisedto6weeksoftreatmentwithfixedcombinationtabletsofcandesartancilexetilandHCTZ16/12.5mgorlosartanandHCTZ50/12.5mg(treatmentallocationwasmadeona1:1ratiowithrandomblocksoftwo).Thestudydesignisillustratedinfigure1.Sincetheformulationsofthestudydrugshaddifferentshapes,thedouble-dummytechniquewasusedforblindingpurposeswithidentical