傲坦研究汇总产品知识奥美沙坦.ppt

傲坦研究汇总,傲坦主要研究汇总,1.OparilS,etal.JClinHypertens.2019;3:283-291,318.；2.SmithDHGetal.AmJCVDrugs.2019;5(1):41-50；3.ChrysantSGetal.AmJHypertens.2003;17:425-432：4.JHypertension2019,23sup(2)S381;5.JClinHypertens.2019;6:168-174;6.TherAdvCardiovascDis2019;1(2):97106;7.AmJHypertens2019;,Oparilstudy,研究介绍,1）随机，双盲，多中心研究2）美国，588例患者袖带坐位DBP:100115mmHgABPM:白天DBP90120mmHg3)首要终点：8周时，袖带DBP相比基线血压的变化4）次要终点：2周，4周时，袖带DBP相比基线血压的变化；2周，4周，8周时，袖带SBP相比基线血压的变化8周时，ABPM监测到的平均DBP相比基线血压的变化.,安慰剂,8周,4周,氯沙坦50mg,厄贝沙坦150mg,OLM20mg,缬沙坦80mg,评价,OparilSetal.JClinHypertens.2019;3:285-291,318.,研究设计,入选标准:袖带坐位DBP:100115mmHgABPM:白天DBP90120mmHg,2周时，傲坦是唯一以初始剂量舒张压和收缩压降幅都达到二位数的ARB,*P0.05vs.olmesartanmedoxomil.OLMolmesartanmedoxomil;LOSlosartanpotassium;VALvalsartan;IRBirbesartanOparilS,etal.JClinHypertens.2019;3:283-291,318.,OLM20mg,MeaninBP(mmHg),LOS50mg,VAL80mg,IRB150mg,*,*,坐位DBP,OLM20mg,LOS50mg,VAL80mg,IRB150mg,*,*,*,坐位SBP,0-2-4-6-8-10-12-14,-10.7,-9.0,-7.6,-9.0,0-2-4-6-8-10-12-14,-13.0,-9.2,-8.9,-10.8,*,*SignificantvsolmesartanmedoxomilMeanbaselineBP:155-157/104mmHgSeDBP:seateddiastolicbloodpressureSeSBP:seatedsystolicbloodpressure,OparilS,etal.JClinHypertens.2019;3:283-291,318.,OLM:olmesartanmedoxomilLOS:losartanpotassiumVAL:valsartanIRB:irbesartan,8周时相比其他ARB,傲坦血压降幅最大,MeaninBP(mmHg),*,*,P=0.0002,P0.001,P=0.041,*,SeSBP,OLM20mg/d(n=145),LOS50mg/d(n=146),VAL80mg/d(n=142),IRB150mg/d(n=145),MeaninBP(mmHg),8周后，OLM坐位DBP降幅最大,*P0.05vs.olmesartanmedoxomil.AdaptedfromOparilS,etal.JClinHypertens.2019;3:283-291,318.,olmesartanmedoxomil,losartanpotassium,valsartan,irbesartan,50mg(n=146),80mg(n=142),150mg(n=145),20mg(n=145),*,*,*,46%,40%,16%,0-2-4-6-8-10-12,DDBP(mmHg),8周后，OLM坐位DBP降幅最大,*P0.05vs.olmesartanmedoxomil.AdaptedfromOparilS,etal.JClinHypertens.2019;3:283-291,318.,olmesartanmedoxomil,losartanpotassium,valsartan,irbesartan,50mg(n=146),80mg(n=142),150mg(n=145),20mg(n=145),*,*,*,3.3mmHg,3.6mmHg,1.6mmHg,0-2-4-6-8-10-12,DDBP(mmHg),在第八周时ABPM舒张压变化(以时间段落观察),0,-10,-2,-12,-4,-6,-8,24小时,-8.5,-6.2,-5.6,-7.4,-10.2,-7.2,-7.0,-8.8,-6.8,-5.2,-4.2,-5.9,-7.1,-5.8,-3.2,-5.4,-6.8,-5.4,-3.1,-4.9,*p0.01(vsolmesartan),*p0.001(vsolmesartan)SmithDHGetal.AmJCVDrugs.2019;5(1):41-50,傲坦20mg/day(n=136)氯沙坦50mg/day(n=134)纈沙坦80mg/day(n=130)厄贝沙坦150mg/day(n=134),*,*,*,*,*,*,*,DBP(mmHg),白天(8:00-19:59),晚上(20:00-7:59),最后2小时(6:00-7:59),最后4小时(4:00-7:59),在第八周时ABPM收缩压变化(以时间段落观察),0,-10,-2,-12,-4,-14,-6,-8,24-hour,SBP(mmHg),傲坦20mg/day(n=136)氯沙坦50mg/day(n=134)纈沙坦80mg/day(n=130)厄贝沙坦150mg/day(n=134),-12.5,-9.0,-8.1,-11.3,-14.7,-10.9,-10.2,-13.8,-10.3,-6.1,-7.3,-8.8,-10.1,-6.9,-5.1,-7.7,-9.8,-7.1,-4.7,-7.4,*p0.05(vsolmesartan),*p0.01(vsolmesartan),*p0.001(vsolmesartan)SmithDHGetal.AmJCVDrugs.2019;5(1):41-50,*,*,*,*,*,*,*,*,*,*,*,白天(8:00-19:59),晚上(20:00-7:59),最后2小时(6:00-7:59),最后4小时(4:00-7:59),140/90mmHg,130/85mmHg,30.1,14.2,13.8,23.9,0,10,20,30,40,50,60,52.9,40.3,35.4,47,0,10,20,30,40,50,60,患者比例(%),OLM20mg/d(N=136),LOS50mg/d(N=134),VAL80mg/d(N=130),IRB150mg/d(N=134),*,*,P=0.330,P=0.004,P=0.038,P=0.247,P=0.002,P=0.002,*,*,OLM20mg/d(N=136),LOS50mg/d(N=134),VAL80mg/d(N=130),IRB150mg/d(N=134),起始剂量的ARB疗效比较第八周时24小时血压达标率,*Significantvs.olmesartanmedoxomil,Nonsignificantvs.olmesartanmedoxomil,SecondaryanalysisMeanbaselineBP:156-157/104mmHgOLMolmesartanmedoxomil,LOSlosartanpotassium,VALvalsartan,IRBirbesartanSmithDHGetal.AmJCVDrugs.2019;5(1):41-50,8周时，傲坦夜间血压降幅最大,*p0.005;p0.05vsolmesartan,*,*,Opariletal.JClinHypertens2019;3:283291,ChangeinABP(mmHg),ABP=ambulatorybloodpressure,8周时，傲坦24小时的最后4小时血压降幅最大,Smithetal.AmJCardiovascDrugs2019;5(1):4150,*p0.001;p0.05vsolmesartan,*,*,ABP=ambulatorybloodpressure,ChangefrombaselineinABP(mmHg),8周时，傲坦24小时的最后2小时血压降幅最大,*,*,ABP=ambulatorybloodpressure,*p0.001;p0.05vsolmesartan,Smithetal.AmJCardiovascDrugs2019;5(1):4150,ChangefrombaselineinABP(mmHg),次晨,次晨,-20,-16,-12,-8,-4,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,-16,-12,-8,-4,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,olmesartanmedoxomil20mg/d,losartan50mg/d,SBP平均变化(mmHg),DBP平均变化(mmHg),24小时坐位SBP/DBP比较奥美沙坦酯与氯沙坦钾,SBPsystolicbloodpressure,DBPdiastolicbloodpressureMeanbaselineBP:152/94-95mmHgSmithDHGetal.AmJCVDrugs.2019;5(1):41-50,次晨,次晨,-20,-16,-12,-8,-4,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,-16,-12,-8,-4,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,olmesartanmedoxomil20mg/d,valsartan80mg/d,SBP平均变化(mmHg),DBP平均变化(mmHg),24小时坐位SBP/DBP比较奥美沙坦酯与缬沙坦,SBPsystolicbloodpressure,DBPdiastolicbloodpressureMeanbaselineBP:152/94-95mmHgSmithDHGetal.AmJCVDrugs.2019;5(1):41-50,次晨,次晨,-20,-16,-12,-8,-4,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,-16,-12,-8,-4,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,olmesartanmedoxomil20mg/d,irbesartan150mg/d,MeanChangeinSBP(mmHg),MeanChangeinDBP(mmHg),24小时坐位SBP/DBP比较奥美沙坦酯与厄贝沙坦,SBPsystolicbloodpressure,DBPdiastolicbloodpressureMeanbaselineBP:152/94-95mmHgSmithDHGetal.AmJCVDrugs.2019;5(1):41-50,Chrysant研究,研究介绍,1）随机，双盲，平行组研究2）440例轻中度高血压患者平均年龄：52岁基线血压：袖带SeDBP:100-115mmHgABPM:日间DBP90-119mmHg3）首要终点：8周时，24小时的平均DBP相比基线血压的变化(ABPM监测)4）次要终点：8周时，24小时平均SBP相比基线血压的变化(ABPM监测)8周时，袖带SBP和DBP相比基线血压的变化,研究设计,入选标准:袖带SeDBP:100-115mmHgABPM:日间DBP90-119mmHgN=440,4weeks,8weeks,安慰剂,OLM20mgqd,氨氯地平5mgqd,安慰剂导入,SeDBP,seateddiastolicbloodpressure;ABPM,ambulatorybloodpressure.ChrysantSGetal.JHumHypertens.2019;17(6):425-432.,24小时动态血压下降幅度与氨氯地平相当,*,*,安慰剂(n=54),OLM20mg(n=171),氨氯地平5mg(n=172),24-hrABPM,DBP(mmHg),SBP(mmHg),安慰剂(n=54),24-hrABPM,OLM20mg(n=171),氨氯地平5mg(n=172),DBP,SBP,*,AdditionalstudywasperformedwitholmesartanmedoxomilversustheDHP-CCBfelodipinewithsimilarresults.,*,0,-2,-4,-6,-8,-10,-12,-14,-12,-10,-8,-6,-4,-2,0,*P0.05vs.placebo,NSforolmesartanmedoxomilvs.amlodipineMeanbaselineBP:154/95-96mmHgChrysantSGetal.JHumHypertens.2019;17(6):425-432.,-2.3,-12.2,-12.3,-1.4,-7.7,-7.0,8周时24小时动态血压达标患者傲坦组多于氨氯地平组,*P=0.0002vs.amlodipineChrysantetal.BloodPressMonit2019;11:135141,*,降压幅度与达标率不一致的原因,HypotheticalExperiment,HypotheticalPatient1100-2080,OlmesartanMedoxomil,HypotheticalPatient2100-1684,BaselineDBP(mmHg)DBP(mmHg)Avg.DBP(mmHg)AchievedDBP(mmHg)AchievedDBPGoal90mmHg85mmHg,-18,-18,Therearemorepatientswith“great”BPreductioninolmesartangroupthaninamlodipinegroup,降压幅度与达标率不一致的原因,Unpublisheddata,*p0.001vsplacebop0.05vsplacebo,*,*,*,*,PatientsachievingBPtarget(%),ChangeinBP(mmHg),2周时，相比氨氯地平傲坦降压降压幅度更大，达标率更高,Basile20:169175,荟萃分析,所有ARB药物在24小时内的降压效果,0,-2,-4,-6,-8,-10,-12,-14,缬沙坦,厄贝沙坦,坎地沙坦,替米沙坦,依普罗沙坦,傲坦,氯沙坦,安慰剂,ChangeinSBP(mmHg),Fabiaetal.JHypertension2019;25:132736,0,-2,-4,-6,-8,-10,ChangeinDBP(mmHg),P=0.03,P=0.002,荟萃分析介绍,这项荟萃分析回顾了已经发表的35篇关于动态血压检测的研究,涉及的药物有:ARB单药治疗(N=7040)安慰剂(N=601)氨氯地平(N=1067)依那普利(N=606)观测了每种药物24小时的血压变化,包括白天,晚上,以及最后4小时,Fabiaetal.JHypertension2019;25:13271336,荟萃分析介绍,用到的ARB的剂量:坎地沙坦816mg/day依普罗沙坦600900mg/day厄贝沙坦150300mg/day氯沙坦50100mg/day奥美沙坦酯2040mg/day替米沙坦4080mg/day缬沙坦80160mg/day其他的降压药:氨氯地平510mg/day依那普利2040mg/day利尿剂2550mg/day,Fabiaetal.JHypertension2019;25:13271336,所有ARB药物在24小时最后4小时的降压效果,Fabiaetal.JHypertension2019;25:13271336,ChangeinDBP(mmHg),ChangeinSBP(mmHg),P=0.04,P=0.02,Captopril12.5mgbid*,Olmesartan5mg*,0,4,12,8,*4周和8周时，如果降压无效，则剂量加倍,傲坦与卡托普利降压比较,随机，对照研究傲坦5-20mg与卡托普利12.5-50mg相比入组患者：291例，平均舒张压95114mmHg,Balletal.JHypertens2019;19(Suppl1):S49S56Stumpe16(Suppl2):S24S28,安慰剂,3周,评价,Week,N=148meanSeDBP101.0mmHg,N=143meanSeDBP102.1mmHg,12周时，傲坦与卡托普利相比DBP/SBP降幅更大,*p0.05vscaptopril,Balletal.JHypertens2019;19(Suppl1):S49S56Stumpe16(Suppl2):S24S28,ChangeinBP(mmHg),*,*,Greathouse.CHF2019;8:31320,ARB初始剂量+HCTZ12.5mg/天,傲坦单药,11,281例患者43个已发表的随机对照研究,-9.9,-12.4,-12.0,-13.6,seDBP(mmHg),0-2-4-6-8-10-12-14,Losartan50mg/d,Valsartan80mg/d,Irbesartan150mg/d,Candesartan8mg/d,-12.2,Olmesartan20mg/d,-13.1,Olmesartan40mg/d,2693例患者7个随机对照研究,傲坦20mg单药血压降幅相当于其他ARB单药+HCTZ,EUTOPIASTUDYEuropeanTrialonOlmesartanandPravastatininInflammationandAtherosclerosis奥美沙坦降低炎症因子的研究,FliserCetal.Circulation.2019;110:11031107,EUTOPIA研究设计,Fliseretal.Circulation.2019;110:11031107.,EUTOPIA研究结果炎症因子降低,*p0.02,*p0.05,#p0.01vs.baseline,p0.05olmesartanvs.placeboFliseretal.Circulation.2019;110:11031107.,OlmesartanPlacebo,week6week12,OlmesartanPlacebo,hsCRP（超敏C反应蛋白）,hsTNF-alpha（肿瘤坏死因子）,OlmesartanPlacebo,week6week12,OlmesartanPlacebo,*,#,*,*,EUTOPIA研究结果炎症因子降低,*p0.02,*p0.05,#p0.01vs.baseline,p130/85mmHg增加其它降压药物,4,奥美沙坦40mgqd,安慰剂,降压药物作为基础治疗,ACE-Iisacceptableunderthesameconditionofdosageandadministrationpriortothetreatmentperiod*OtherantihypertensivesmeansexcludingARBs,potassium-sparingdiuretics,尿白蛋白与肌酐比,新的大规模预防性研究ROADMAPRANDOMISEDOLMESARTANANDDIABETESMICROALBUMINURIAPREVENTIONSTUDY,奥美沙坦预防糖尿病微量蛋白尿的随机临床试验,ROADMAP,目标:预防或推迟有风险因素的2型糖尿病病人发生微量蛋白尿病人类别和样本规模:2型糖尿病病人伴正常白蛋白尿，存在至少一项心肾疾病的风险因素。每组2200个病人(奥美沙坦40mgQD或安慰剂)，统计的325个主要终点事件(检测到33%的风险因素减少)。随访:中位数5年区域:欧洲的22个国家280个研究中心,SummaryofROADMAPPost-hocAnalysis,page76,SecondaryEndpoint,CardiovascularEvents,RenalEventsHypertensivesub-population,复傲坦研究汇总,OLM与3种ARB联合用药荟萃分析,厄贝沙坦37.5300mg/HCTZ6.25-25mg(N=683),缬沙坦80160mg/HCTZ12.5-25mg(N=871),Olmesartan1040mg/HCTZ12.5-25mg(N=502),替米沙坦4080mg/HCTZ12.5mg(N=818),4项独立,双盲的研究,每个研究都是以第8周时平均DBP相比基线值的变化作为主要观察指标患者都接受了安慰剂,ARBHCTZ的治疗在最后一次给药后的24小时观察血压变化DBP的平均基线:100104.4mmHgSBP的平均基线:151156.6mmHg,介绍,安慰剂,8周,24周安慰剂导入,Ram.JClinHypertens2019;6: