高血压合理用药最新要点讨论及处方分析

高血压合理用药最新要点讨论及处方分析顼志敏XuZhimin中国医学科学院阜外心血管病医院我国高血压患病率愈来愈高百分比*(%)04812162019591814106219791991200218.8%全国患病人数已超过2.0亿中国居民营养与健康现状调查。卫生部、科技部、统计局，2004、10、12»我国18岁及以上居民高血压患病率为18.8%6.1％~8%24.7％30.2％1.6亿18.8％2004年全国营养与健康综合调查（18岁）2.9％12.2％26.6％9400万11.26％1991年全国抽样调查(15岁以上)控制率服药率知晓率患病人数患病率中国高血压控制率降压本身的益处平均降低卒中发生率35–40%心肌梗死20–25%心力衰竭50%JNC7收缩压降低10–12mmHg或舒张压降低5-6mmHg1、高血压治疗四大目标长期、有效、平稳控制血压水平预防(逆转)心、脑、肾等靶器官的损害减少心、脑血管疾病的发病和死亡——循证医学改善生活质量亚临床靶器官损害之保护(2009,octESHReappraisal)Evidenceontheimportantprognosticroleofsubclinicalorgandamagecontinuestogrow.Inbothhypertensivepatientsandthegeneralpopulation,thepresenceofelectrocardiographicandechocardiographicLVH,acarotidplaqueorthickening,anincreasedarterialstiffness,areducedeGFR(assessedbytheMDRDformula),ormicroalbuminuriaorproteinuriasubstantiallyincreasesthetotalcardiovascularrisk,usuallymovinghypertensivepatientsintothehighabsoluteriskrange.合并亚临床靶器官损害常为高危者：LVH,颈动脉斑块、增厚硬化，eGFR下降，微量/蛋白尿。----JournalofHypertension2009,27:2121–2158血压目标所有患者140/90140/90DM/肾病130/80(DM)130/80冠心病：130/80mmHg(2007/2009年欧洲高血压指南)*老年SBP难于140可适当灵活些(尤低危者)，老年收缩压可降至150mmHg以下血压目标——低限？(ESHJune,2009)Keyamongthechangeswillbetherecommendationofalowerthresholdlevel--around120mmHgsystolicand70mmHgdiastolic--belowwhichitcouldbedangeroustoreducebloodpressureinhigh-riskindividuals,representingtheso-calledJ-curvephenomenon,Manciasaid.J-Curve:ANarrowWindowofOptimumBPforHigh-RiskIndividuals“J形曲线”可能存在，有些特定高危患者血压不宜过低（120/70）----June16,2009(Milan,Italy)—TheEuropeanSocietyofHypertension(ESH)血压达标(2009,octESHReappraisal)Eachdrugclasshascontraindicationsaswellfavorableeffectsinspecificclinicalsettings.Thechoiceofdrug(s)shouldbemadeaccordingtothisevidence.Thetraditionalrankingofdrugsintofirst,second,third,andsubsequentchoice,withanaveragepatientasreference,hasnowlittlescientificandpracticaljustificationandshouldbeavoided.每种药物均有利弊：应循证选药；强调个性化用药，避免一线、二线、三线----JournalofHypertension2009,27:2121–2158何时开始用药(2009,octESHReappraisal)itappearsreasonabletorecommendthat,ingrade1hypertensives(SBP140–159mmHgorDPB90–99mmHg)atlowandmoderaterisk,drugtherapyshouldbestartedafterasuitableperiodwithlifestylechanges.Prompterinitiationoftreatmentisadvisableifgrade1hypertensionisassociatedwithahighlevelofrisk,orifhypertensionisgrade2or3.立即用药：a）2或3级高血压;b）1级HT+高危改善生活方式后用药：1级HT+低、中危2、治疗策略（中国）几周内渐降血压至目标,更长/更短期间？（几天？）推荐长效剂，持续24小时、T/P50%，Qd，提高顺从、平稳降压据血压水平、RF、TOD、ACC,选单或多药联合制定个性化方案：2级以上高血压常需联合用药，配合非药物疗法达标快慢：(2009,JuneESH)In2007,wetookastrongstanceinfavorofcombinationtreatment.Thishasbeenshownagain--trialssuchasACCOMPLISH,ADVANCE,HYVET,ASCOTandONTARGETarechangingthepicture.WehavetolowerBPratherquickly[inthesepatients]totrytopreventacatastrophe,andmorerecently,studieshaveshownthereislessdiscontinuationoftreatmentinthispatientpopulationiftreatmentisstartedwithcombinationtherapy,Manciasaid.对高危患者更倾向于：联合用药、尽快达标、预防事件----June16,2009(Milan,Italy)—TheEuropeanSocietyofHypertension(ESH)3、药物治疗战略理念3-1用药模式：1）套餐模式：1950—60s2）席餐模式:1970—80s3）自助餐模式:1990—2000s3-2常用五类药物及其配方：RAS拮抗剂：ACEI(普利)ARB(沙坦)钙拮抗剂：CCB(地平等)利尿剂(噻嗪等)Beta阻滞剂：BB(洛尔等)2009ESC/ESH专家意见利尿剂CCBARBACEI3-32007ESC/ESH指南推荐联合:①噻嗪类利尿剂与ACEI，②噻嗪类利尿剂与ARB，③钙拮抗剂与ACEI，④钙拮抗剂与ARB，⑤钙拮抗剂与噻嗪类利尿剂，⑥β-受体阻滞剂与二氢吡啶类钙拮抗剂。保护心脑肾作用突出：(2009,octESH)Innolessthan15–20%ofhypertensivepatients,BPcontrolcannotbeachievedbyatwo-drugcombination.Whenthreedrugsarerequired,themostrationalcombinationappearstobeablockeroftherenin–angiotensinsystem,acalciumantagonist,andadiureticateffectivedoses.至少15–20%高血压患者，需要三联用药：最合理方案：RAS拮抗剂+CCB+利尿剂----JournalofHypertension2009,27:2121–2158合理联合用药方案：(2009,octESH)Thecombinationoftwoantihypertensivedrugsmayofferadvantagesalsofortreatmentinitiation,particularlyinpatientsathighcardiovascularriskinwhichearlyBPcontrolmaybedesirable.Wheneverpossible,useoffixeddose(orsinglepill)combinationsshouldbepreferred,becausesimplificationoftreatmentcarriesadvantagesforcompliancetotreatment.在高危病人，两药联合还可尽快达标应优先应用固定剂量的单片剂复方：使治疗简化、顺应性提高4-2、2007欧洲高血压指南:长效钙通道阻滞剂：没有强制禁忌证。推荐用于:脑卒中、老年单纯收缩期高血压、心绞痛、左室肥厚、颈动脉或冠状动脉粥样硬化、妊娠妇女、黑人高血压等。ACEI/ARB类药物的绝对禁忌证妊娠血管神经性水肿高钾血症双侧肾动脉狭窄4-2、2007欧洲高血压指南:ACEI：ACEI优先适应证共10项：心力衰竭、左室肥厚、左室功能异常、心肌梗死后、糖尿病肾病、非糖尿病肾病、颈动脉粥样硬化、蛋白尿或微量蛋白尿、心房颤动和代谢综合征等4-2、2007欧洲高血压指南:ARB优先适应证：1.老年患者2.糖尿病3.肾功能不全4.脑卒中5.冠心病和心衰6.房颤7.代谢综合征Beta阻滞剂：(2009,JuneESH)Thetotalityofevidencenowshowsdifferentconclusionsfordifferentpatientpopulations,hesaid.Forexample,forstrokeprevention,betablockersareinferiortocalciumantagonists,butforcongestiveheartfailureprevention,betablockersaresuperiortocalciumantagonistsandsimilartootherdrugs,对脑卒中预防，BB弱于CCB;对心衰，BB强于CCB----June16,2009(Milan,Italy)—TheEuropeanSocietyofHypertension(ESH)Beta阻滞剂：(2009,octESH)arecentmeta-analysisof147randomizedtrials(thelargestmeta-analysissofaravailable)reportsonlyaslightinferiorityofb-blockersinpreventingstroke(17%reductionratherthan29%reductionwithotheragents),butasimilareffectasotheragentsonpreventingcoronaryeventsandheartfailure,andahigherefficacythanotherdrugsinpatientswitharecentcoronaryevent目前最大（n=147）RCT荟萃分析示：与其他药物比，Beta阻滞剂，预防脑卒中方面略弱；预防冠脉事件和心衰，相同；预防近期冠脉事件，较好。RAS拮抗剂：(2009,octESH)ONTARGEThasshow