厄贝沙坦治疗马凡综合征疗效显著
2019-12-17   阅读:464   来源:Thelancet

英国东英吉利大学MarcusFlather研究小组发现厄贝沙坦可有效治疗马凡氏综合征。2019年12月10日,国际知名学术期刊《柳叶刀》发表了这一成果。

厄贝沙坦是一种长效选择性血管紧张素-1受体抑制剂,用于治疗马凡综合征可能会减少动脉扩张,而动脉扩张易导致夹层和破裂。

2012年3月14日至2015年5月1日,研究组在英国的22个中心进行了一项安慰剂对照、双盲、随机试验,共招募了192名6-40岁的马凡综合征患者。所有参与者每天均服用75mg的厄贝沙坦,在此基础上随机分组,104名每天服用150mg的厄贝沙坦,88名服用安慰剂。采用超声心动图对主动脉直径进行测量。

192名参与者的中位年龄为18岁,52%为女性,108名服用β受体阻滞剂。厄贝沙坦组和安慰剂组的平均基线主动脉根部直径为34.4mm。随访5年后,厄贝沙坦组主动脉根部扩张的平均速率为0.53mm/年,而安慰剂组为0.74mm/年,差异显著。厄贝沙坦还降低了主动脉Z评分的变化率,耐受性良好,严重不良事件的发生率与安慰剂相比无明显差异。

总之,厄贝沙坦可降低马凡综合征患儿和青年的主动脉扩张率,进一步降低了主动脉并发症的发生率。

附:英文原文

Title:IrbesartaninMarfansyndrome(AIMS):adouble-blind,placebo-controlledrandomisedtrial

Author:MichaelMullen,XuYuJin,AnneChild,AGrahamStuart,MatthewDodd,JoséAntonioAragon-Martin,DavidGaze,AnatoliKiotsekoglou,LiYuan,JiangtingHu,ClaireFoley,LauraVanDyck,RosemaryKnight,TimClayton,LornaSwan,JohnDRThomson,GulizErdem,DavidCrossman,MarcusFlather,JohnDean,BartoszWas,HeatherGow,JaneMurray,MariellaDAllessandro,MichaelChristie,PatriciaCooper,PhilipBooth,SharonBurns,YvonnePaterson,AshishChikermane,AnthonyAssing,CatherineCotter,GillianAtkins,HelenWilliamson,JustinBarclay,AlanJennison,AlexHenderson,AnnaMcSkeane,HelenFairlamb,JulieKelly,NicolaKelsall,ScottPrentice,JohnOSullivan,AlisonHead-Baister,AngelaPhillipson,AnnaJohnson,DCrossland,JackOliver,JadeDavison,JillWake,LouiseQuinn,MaureenForeman,VeraWealleans,NikiWalker,AlexisDuncan,EvelynTibbs,RuthKelly,SachinKhambadkone,BridgetZotti,CassieBrady,ElenaCervi,EllaField,EszterSzepezvary,FlorenceMantey,GillianRiley,HeatherTitmus,IlariaBo,JuanPabloKaski,LorenGreen,NigelJones,RebeccaBanks,ChristopherKiesewetter,SujeevMathur,AlessandraFrigiola,AlexSavis,HollyBelfield,JosephineGuzman,JuliaHarris,KarenWilson,KellyPeacock,KirstyGibson,PaulWellman,JohnSimpson,SalehaKabir,SitaliMushemi,MichaelStewart,BevAtkinson,CathRichardson,ElaineLeng,PaulBrennan,AnnabelNixon,ColletteSpencer,JamesOliver,JanForster,LouiseTurner,SamanthaBainbridge,AnnaMariaChoy,AdelleDawson,GwenKiddie,HeatherKerr,IfyMordi,JackieDuff,JacquelineDunlop,JonathanBerg,PaulineArmory,LeisaFreeman,AmirAnwar,CharlesGraham,ClareLondon,GailHealey,IanGallagher,MaryIlsley,RizwanAhmed,SheilaWood,NigelWheeldon,CeciliaMason,FarookNassim,JanetMiddle,JustinAdams,KarenAngelini

Issue&Volume:December10,2019

Abstract:

Background

Irbesartan,alongactingselectiveangiotensin-1receptorinhibitor,inMarfansyndromemightreduceaorticdilatation,whichisassociatedwithdissectionandrupture.WeaimedtodeterminetheeffectsofirbesartanontherateofaorticdilatationinchildrenandadultswithMarfansyndrome.

Methods

Wedidaplacebo-controlled,double-blindrandomisedtrialat22centresintheUK.Individualsaged6–40yearswithclinicallyconfirmedMarfansyndromewereeligibleforinclusion.Studyparticipantswereallgiven75mgopenlabelirbesartanoncedaily,thenrandomlyassignedto150mgofirbesartan(increasedto300mgastolerated)ormatchingplacebo.Aorticdiameterwasmeasuredbyechocardiographyatbaselineandthenannually.Allimageswereanalysedbyacorelaboratoryblindedtotreatmentallocation.Theprimaryendpointwastherateofaorticrootdilatation.ThistrialisregisteredwithISRCTN,numberISRCTN90011794.

Findings

BetweenMarch14,2012,andMay1,2015,192participantswererecruitedandrandomlyassignedtoirbesartan(n=104)orplacebo(n=88),andallwerefollowedforupto5years.Medianageatrecruitmentwas18years(IQR12–28),99(52%)werefemale,meanbloodpressurewas110/65mmHg(SDs16and12),and108(56%)weretakingβblockers.Meanbaselineaorticrootdiameterwas34·4mmintheirbesartangroup(SD5·8)andplacebogroup(5·5).Themeanrateofaorticrootdilatationwas0·53mmperyear(95%CI0·39to0·67)intheirbesartangroupcomparedwith0·74mmperyear(0·60to0·89)intheplacebogroup,withadifferenceinmeansof−0·22mmperyear(−0·41to−0·02,p=0·030).TherateofchangeinaorticZscorewasalsoreducedbyirbesartan(differenceinmeans−0·10peryear,95%CI−0·19to−0·01,p=0·035).Irbesartanwaswelltoleratedwithnoobserveddifferencesinratesofseriousadverseevents.

Interpretation

IrbesartanisassociatedwithareductionintherateofaorticdilatationinchildrenandyoungadultswithMarfansyndromeandcouldreducetheincidenceofaorticcomplications.

DOI:10.1016/S0140-6736(19)32518-8

#马凡氏综合征
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