高血壓的治療：新的循環(huán)醫(yī)學(xué)證據(jù)

高血壓治療

新的循證醫(yī)學(xué)證據(jù)華中科技大學(xué)協(xié)和醫(yī)院心內(nèi)科廖玉華高血壓治療：新的循證醫(yī)學(xué)證據(jù)ADVANCE研究—固定復(fù)方制劑VALIDD研究—降壓與心室舒張功能Ameta-analysisofRCTs中國(guó)人高血壓臨床試驗(yàn)證據(jù)ADVANCE研究:

在11,140例2型糖尿病患者中進(jìn)行的降壓與強(qiáng)化血糖控制的析因隨機(jī)臨床試驗(yàn)培哚普利吲達(dá)帕胺固定復(fù)方制劑（百普樂）對(duì)重要血管事件的影響Inclusioncriteria

Type2diabetesmellitusAge55yearsorolderAdditionalriskofvasculareventAge

65yearsHistoryofmajormacrovasculardiseaseHistoryofmajormicrovasculardiseaseFirstdiagnosisofdiabetes>10yearspriortoentryOthermajorriskfactorHypertensiveornormotensiveRandomisedstudytreatmentsBloodpressureloweringDouble-blindperindopril-indapamide

versusmatchingplacebo2.0/0.625mgorplaceboforfirst3months4.0/1.25mgorplacebothereafterBloodglucoselowering(ongoing)Open-labelgliclazideMR-basedintensivetherapytargetinganHbA1cof6.5%versususualguideline-basedcareAmongpatientswithdiabetes,doesbloodpressureloweringtherapy:Produceadditionalbenefitswhensystolicpressureisloweredbelow145mmHg?Producesimilarbenefitsforhypertensiveandnon-hypertensivepatients?AddtothebenefitsproducedbyothercardiovascularpreventivetherapiesincludingACEinhibitors?ADVANCEstudyhypotheses

Perindopril-indapamidearmADVANCE

Trialprofile12877withtype2diabetesregistered11140randomised5569assignedperindopril-indapamidecombination1737withdrewduringrun-inScheduledendoffollow-up:4.3years4908(88%)assessedatfinalvisit4081(73%)adherenttotreatment4losttofollow-up11losttofollow-upScheduledendoffollow-up:4.3years4863(87%)assessedatfinalvisit4143(74%)adherenttotreatment5571assignedmatchingplacebo血壓降低情況Δ2.2mmHg(95%CI2.0-2.4);p<0.001Δ

5.6mmHg(95%CI5.2-6.0);p<0.001DiastolicSystolic安慰劑組培哚普利/吲達(dá)帕胺組MeanBloodPressure(mmHg)65758595105115125135145155165Follow-up(Months)R6121824303642485460140.3mmHg134.7mmHgAverageBPduringfollow-up77.0mmHg74.8mmHg全因死亡率Follow-up(months)01006121824303642485460

安慰劑組

培哚普利/吲達(dá)帕胺組Cumulativeincidence(%)Relativeriskreduction14%:95%CI2-25%p=0.0255死亡分析心血管死亡Follow-up(months)6121824303642485460安慰劑組培哚普利/吲達(dá)帕胺組非心血管死亡Follow-up(months)6121824303642485460安慰劑組培哚普利/吲達(dá)帕胺組相對(duì)危險(xiǎn)降低18%;p=0.027相對(duì)危險(xiǎn)降低8%;p=0.415%5%Cumulativeincidence(%)Coronaryevents*2P=0.02?Non-fatalMIordeathfromcoronaryheartdisease?Unstableanginarequiringhospitalisation,coronaryrevascularisationorsilentMIMajorcoronaryheartdisease?26529411%(-6to24)Allcoronaryheartdisease468535

14%(2to24)Othercoronaryheartdisease?28332414%(-1to27)*NumberofeventsPer-IndPlacebo(n=5,569)(n=5,571)Relativeriskreduction(95%CI)FavoursPer-IndFavoursPlaceboHazardratio0.51.02.0CerebrovasculareventsMajorcerebrovasculardisease?2152182%(-18to19)Allcerebrovasculardisease2863036%(-10to20)Othercerebrovasculardisease?799921%(-6to41)2.0**2P=0.40?Non-fatalstrokeordeathfromcerebrovasculardisease?TransientischaemicattackorsubarachnoidhaemorrhageNumberofeventsPer-IndPlacebo(n=5,569)(n=5,571)Relativeriskreduction(95%CI)FavoursPer-IndFavoursPlaceboHazardratio0.51.0Renalevents2.0Hazardratio0.51.0Neworworseningnephropathy18121618%(-1to32)Newmicroalbuminuria1094131721%(14to27)Totalrenalevents1243150021%(15to27)**2P=<0.01NumberofeventsPer-IndPlacebo(n=5,569)(n=5,571)Relativeriskreduction(95%CI)FavoursPer-IndFavoursPlacebo經(jīng)過5年治療可預(yù)防事件數(shù):每治療患者例數(shù)1例主要血管事件66例1例死亡79例1例冠脈事件75例1例腎臟事件*20例*多為新發(fā)微量白蛋白尿常規(guī)使用培哚普利與吲達(dá)帕胺的絕對(duì)獲益總結(jié)2型糖尿病患者常規(guī)使用培哚普利/吲達(dá)帕胺治療的結(jié)果:總死亡率降低14%心血管死亡降低18%主要血管事件降低9%總冠脈事件降低14%總腎臟事件降低21%這些獲益在所有主要亞組都相似。治療的耐受性非常好，副作用很少，遵從治療的情況與安慰劑組相似。Amongpatientswithdiabetes,doesbloodpressureloweringtherapy:Produceadditionalbenefitswhensystolicpressureisloweredbelow145mmHg?Producesimilarbenefitsforhypertensiveandnon-hypertensivepatients?AddtothebenefitsproducedbyothercardiovascularpreventivetherapiesincludingACEinhibitors?Bloodpressureloweringindiabetes:

Unresolvedissues2000YESYESYESVALIDD研究TheInfluenceofAngiotensinReceptorBlockersandBloodPressureLoweringonDiastolicFunctioninPatientswithHypertensionandDiastolicDysfunction:TheVALsartanInDiastolicDysfunction

血管緊張素受體拮抗劑(ARB)對(duì)高血壓和舒張功能不全患者的作用

SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.研究目的目的:驗(yàn)證下列假說是否正確“ARB較其他非阻斷RAAS系統(tǒng)的降壓藥物更有效改善左室舒張功能”？SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.研究設(shè)計(jì)482例初選患者年齡大于45歲、1、2級(jí)高血壓、無心功能不全病史組織多普勒檢查，評(píng)價(jià)心肌舒張速度，確定舒張功能不全的存在384例舒張功能不全的患者纈沙坦組(n=186)320mg/d非RAAS拮抗劑降壓治療(n=198)鈣拮抗劑、利尿劑、?阻滯劑隨機(jī)分組觀察終點(diǎn)38周前后的舒張速度、等容舒張時(shí)間（S’)、加速時(shí)間、E/A、E/E’左室容積質(zhì)量、射血分?jǐn)?shù)隨訪38周SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.ARBvs.非RAAS阻斷劑組:降壓幅度相當(dāng)38周后,兩組的血壓較基線相比降低幅度沒有顯著差異收縮壓較基線的改變(mmHg)纈沙坦組(n=186)非RAAS阻斷劑組(n=198)p=NS

SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.ARBvs.非RAAS阻斷劑組:改善舒張功能療效相當(dāng)38周后,ARB和非RAAS阻斷類降壓藥物均顯著改善舒張功能，療效相當(dāng)時(shí)間/治療前后的變化心肌舒張速度(cm/s)纈沙坦(n=186)非RAAS阻斷劑組(n=198)基線7.57.5治療38周后8.1*8.0*心肌舒張速度提高0.66**0.44*每組治療前后比較P<0.0001,**組間比較P=NSSolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.研究結(jié)論輕中度高血壓患者雖然左室肥厚發(fā)生率低，但已經(jīng)存在心肌舒張功能不全，這是高血壓靶器官受累的早期標(biāo)志，進(jìn)而將導(dǎo)致左室肥厚在降壓療效相同時(shí)，ARB和非RAAS阻斷類降壓藥物均顯著改善心肌舒張功能，療效相同降壓治療帶來又一項(xiàng)收益，即改善舒張功能。即便是輕中度高血壓患者，也可受益SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.VALIDD評(píng)論50%高血壓患者存在舒張功能不全，雖然部分患者最終進(jìn)展為心衰，但是迄今仍然沒有具備針對(duì)性的治療方法。VALIDD研究證實(shí)降低血壓可有效改善舒張功能不全，即使輕中度高血壓患者也可獲益。這一結(jié)果說明：對(duì)于高血壓患者，應(yīng)該采取積極降壓措施－－DrScottSolomon，VALIDD研究領(lǐng)導(dǎo)人，布萊根女子醫(yī)院，哈佛醫(yī)學(xué)院PreventionofstrokeandMIbyamlodipineandARBs氨氯地平與ARBs預(yù)防卒中與心肌梗死Ameta-analysisofRCTs隨機(jī)對(duì)照臨床試驗(yàn)綜合分析WangJGetal.Hyp