临床研究和心力衰竭的治疗策略医学课件.ppt

1、1900s个人经验个人经验权威性教学权威性教学无对照病例报告无对照病例报告病例对照研究临床试验病例对照研究临床试验以科学为本的病因学以科学为本的病因学1970s临床终点研究临床终点研究+临床经验临床经验以证据为本的临床用药以证据为本的临床用药2019传统医学传统医学循证医学循证医学1 1证据来源证据来源动物实验、体外实验等实验室研究零散临床研究、过时的教科书临床研究2 2收集证据收集证据不系统不全面系统全面3 3评价证据评价证据不重视重视4 4判效指标判效指标实验室指标的改变仪器或影像学结果（中间指标)病人最终结局（终点指标）5 5治疗依据治疗依据基础研究/动物实验的推论个人临床经验当前可得到

2、的最佳临床研究证据6 6医疗模式医疗模式疾病/医生为中心病人为中心传统医学与循证医学实践模式差异传统医学与循证医学实践模式差异Applying Classification of Recommendations and Level of Evidence 17001700180018001900190020002000DiagnosisDiagnosisMercurialMercurialdiureticsdiureticsLoopLoopdiureticsdiureticsACEiACEiARBsARBsBBsBBs年代年代TheCONSENSUSTrialStudyGroup.N Engl

3、 J Med.1987;316:1429-1435.PackerMetal.N Engl J Med.2019;334:1349-1355.PittBetal.N Engl J Med.2019;341:709-717.MossAetal.N Engl J Med.2019;335:1933-1940.1.AbrahamWTetal.N Engl J Med.2019;346:1845-1853.%MenMenWomenWomenp=0.003vs placebop=0.0036vs placebop=0.30vs placebop=0.002vs placebop=0.019vs place

4、bop=0.128high dosevs low dosep=0.001vs placebo16%8%19%27%Risk reduction8%22%27%CONSENSUSSOLVD(treatment)SOLVD(prevention)AIRESAVEATLASTRACE010203040IA全部全部CHF患者必须应用患者必须应用ACEI，包括阶段包括阶段B无症性心衰和无症性心衰和LVEF4045%者，者，除非有禁忌证或不能耐受，除非有禁忌证或不能耐受，ACEI需终身应用需终身应用IAACEI从小剂量开始从小剂量开始,逐渐递增逐渐递增,直至达到目标剂量直至达到目标剂量ACEI与与受体阻滞

5、剂合用有协同作用受体阻滞剂合用有协同作用 EichhornEJ,JCF.2000;6(suppl1):40-46.LVEFTime(months)Biologic EffectPharmacologic Effectb b-Blocker Initiatedb b-Blocker Discontinuedp0.0001p0.0001vs placebovs placebop0.001p0.001vs placebovs placebop=0.0062p=0.0062vs placebovs placebop=0.00013p=0.00013vs placebovs placeboCIBIS-I

6、IInvestigatorsandCommittees.Lancet2019;353:9-13;ColucciWS.Circulation2019;94:2800-6(U.S.Carvedilol)MERITStudyGroup.Lancet 2019;253:2019-6;PackerM.Circulation2019;106:2194-9(COPERNICUS)Beta-blockers in HFcarvedilolMetoprolol XLbisoprololIA所有慢性收缩性心衰，所有慢性收缩性心衰，NYHA、级病情稳定患者，级病情稳定患者，以及阶段以及阶段B、无症状性心衰、无症状性

7、心衰或或NYHA级的患者级的患者(LVEF40%)，均必需应用均必需应用受体阻滞剂，受体阻滞剂，且需终身使用，除非有禁忌证或不能耐受。且需终身使用，除非有禁忌证或不能耐受。极小剂量开始，每极小剂量开始，每24周剂量加倍。周剂量加倍。起始治疗前患者需无明显液体潴留，起始治疗前患者需无明显液体潴留，体重恒定，利尿剂已维持在最合适剂量。体重恒定，利尿剂已维持在最合适剂量。有明显液体潴留，需大量利尿者，暂时不能应用有明显液体潴留，需大量利尿者，暂时不能应用 TitlenPopulationTreatment regimen Data available(est)LosartanELITE760ACEI

8、-naive,elderly,HF monotherapy,50 mg qd 2019ELITE II 2600ACEI-naive,elderly,HFmonotherapy,50 mg qd2019ValsartanVAL-HeFT 5200 ACEI-treated HF combination:ACEI bid,(2000)valsartan,160 mg bidCandesartanCHARM I1700ACEI-intolerant EF40%,monotherapy,4 32 mg qd(2019)NYHA IIIIV CHARM II2300ACEI-treated EF40%

9、,not on ACEI candesartan,432 mg qd(2019)NYHA IIIV*所列药物中坎地沙坦和缬沙坦已有一些临床试验证实，对降低CHF患者死亡率、病残率有益IA不能耐受不能耐受ACEI的的LVEF低下的患者，低下的患者，以减低死亡率和并发症以减低死亡率和并发症 IIbB常规治疗后心衰症状持续存在，常规治疗后心衰症状持续存在，且且LVEF低下者，可考虑加用低下者，可考虑加用ARB p0.0000p0.0000vs placebovs placebop0.0000p0.0000vs placebovs placebop0.0000p0.0000vs placebovs p

10、laceboPittB.N Engl J Med2019;341:709-17RALES,noteB;TrifonovIR.Kardiologiia 2019;43:71-2;CAPRICORNInvestigatorsLancet 2019;357:1385-90Pitt et al.NEJM 2019:341:709.HR 0.70p0.001IB中、重度心衰，中、重度心衰，低低LVEF需严密监测肾功能及血钾需严密监测肾功能及血钾Rate of deathfrom cardiovascular causes or hospitalizationor cardiovascularevents

11、Pitt et al.NEJM 2019;348:1309.IBAMI后并发心衰，后并发心衰，LVEF40%NEJM 2019;336:525.All-cause mortalityDeath or hospitalization for worsening HFIIa B洋地黄制剂对合并有症状洋地黄制剂对合并有症状的低的低LVEF心衰患者，心衰患者，可降低因心衰所致的入院率可降低因心衰所致的入院率Study characteristics of included RCTs of CRT and ICD therapy in left ventricular impairment and sy

12、mptomatic HFLam,S.K H et al.BMJ 2019;335:925Lam,S.K H et al.BMJ 2019;335:925Results of Bayesian network meta-analysis of 12 RCTs of device therapies in 8307 patients with left ventricular dysfunctionLam,S.K H et al.BMJ 2019;335:925CRT IA窦性节律，窦性节律，QRS波群波群120ms，LVEF35%左心室舒张末期内径左心室舒张末期内径(LVEDD)55mm最佳药物

13、治疗后心功能仍为最佳药物治疗后心功能仍为NHYA 级或级或级级Adapted from Chatterjee K.Am J Geriatr Cardiol 2019;11:178-89.CCB=calcium-channel blocker;HR=heart rate*Use with cautionAngiotensinConvertingEnzymeInhibitorSpironolactoneDigoxinNoaddedsalt2gmNaHFclinicsfollow-upCustomizedlifestyleprogramAsymptomaticMild/ModSevereRefrac

14、toryAngiotensinIIReceptorBlocker-Blocker*Excludespatientswithdocumentedcontraindications.2300/7883patientshospitalizedwithHF;priorknowndxofsystolicdysfunctionHF;outpatientmedicalregimen.ADHERERegistryReportQ12019(4/01-3/02)of180UShospitals.PresentedbyGCFonarowattheHeartFailureSocietyofAmericaSatelli

15、teSymposium,September23,2019.LVEF Documented and 0.40*44.31040.96831.90102030405060708090100Outpatient HF MedicationACEInhibitorARBb-BlockerDiureticDigoxinPatients Treated(%)UniversityHospitalConsortiumHFRegistry:33centers,1239patients,Year2000.OutpatientregimenbeforeHFhospitalizationinpatientswithS

16、tageCHF.UnpublisheddataprovidedcourtesyofDrGCFonarow,UCLAMedicalCenter.6929190102030405060708090100ACE Inhibitorsb b-BlockersSpironolactonePatients Treated(%)b b-BlockersInternationalsurvey:15countries,1363physicians,11,062patients:Year2000.OutpatientregimeninpatientswithStageCHF,documentedsystolicd

17、ysfunction.ClelandJG.Lancet.2019;360:1631-1639.603420120102030405060708090100ACE InhibitorsACEI+BBSprionolactonePatients Treated(%)McMurrayJJV.Lancet2019;362(9386):777-81MERIT-HF Study Group.MERIT-HF Study Group.Lancet Lancet 2019;353(9169):2019-72019;353(9169):2019-7SOLVD Investigators.SOLVD Investigators.N Engl J MedN Engl J Med 1991;325(5):293-302 1991;325(5):293-3022019CHARM-AddedSurvival2019(MERIT-HF)1990s(SOLVD)1890s1990sThanks！