心力衰竭药物治疗新证据与新视野.ppt

Click to edit Master title style,Click to edit Master text styles kbb,Second level,Third level,Fourth level,Fifth level,心力衰竭药物治疗,新证据与新视野,200040,治疗心力衰竭的药物,1、强心苷类药物,2、利尿剂,3、,ACE,抑制剂及血管紧张素,II,（AT,1,）,受体拮抗剂,4,、受体阻断剂,5,、其他治疗,CHF,的药物：,（1）,钙拮抗剂,（2）,磷酸二酯酶抑制剂,（3）其他血管扩张剂：长效硝酸酯类，肼苯哒嗪,DIG,研究,50,40,30,20,10,0,Placebo,n=3403,Digoxin,n=3397,48,0,12,24,36,Mortality%,N Engl J Med 1997;336:525,Months,p=0.8,Digitalis,N=6800,NYHA II-III,0.6,Probability of Death,0,Placebo(273),Prazosin(183),Hz+ISDN(186),Months,0.7,0.5,0.3,0.4,0.2,0.1,N Engl J Med 1986;314:1547,Nitrates,0,6,12,18,24,30,36,42,V-HeFT-I,研究,combination of hydralazine(300mg/day)and isosorbide dinitrate(160mg/day,23%reduction in mortality,50,40,30,20,10,0,Months,0,6,12,p =0.0036,%Mortality,24,18,30,36,42,48,Enalapril,n=1285,Placebo,n=1284,N Engl J M 1991;325:293,n=2589,CHF,-NYHA II-III,-EF 35,SOLVD(Treatment),研究,11.3%reduction in mortality,0,54,0,48,0,12,24,48,60,0.75,0.50,0.25,0,0.47,0.36,0.25,0.13,0.09,0.31,0.18,0.42,36,Months,p =0.08,N Engl J Med 1991;325:303,Enalapril,HZ+ISDN,n=804,p =0.016,Probability of death,Nitrate+Hydralazine,Vs,Enalapril,V-HeFT II,研究,卡维地,洛,n=696,安慰剂,n=398,存活,天,0,50,100,150,200,250,300,350,400,危险度下降=65%,p0.001,Packer et al(1996),CIBIS-II Investigators(1999),比索洛尔,安慰剂,接收后的时间(天),p0.0001,存活,危险度下降=34%,The MERIT-HF Study Group(1999),美国,卡维地洛,计划,CIBIS-II,0.8,1.0,0.6,0,随访月,0,3,6,9,12,15,18,21,20,15,10,5,0,安慰剂,美托洛尔,CR,p=0.0062,危险度下降=34%,MERIT-HF,月,0,0,3,6,9,12,15,18,21,100,90,80,60,70,卡维地,洛,安慰剂,危险度下降=35%,存活,Packer et al(2001),哥白尼（,COPERNICUS,）研究,p=0.00013,0.5,0.6,0.7,0.8,0.9,1.0,0,200,400,600,800,死亡率,(%),心力衰竭药物治疗,AsymptomaticMild to moderateModerate,LV dysfunctionCHFto severe CHF,ACE inhibitorDigoxinDigoxin,Beta blockerDiureticsDiuretics,ACE inhibitorACE inhibitor,Beta blockerBeta blocker,Spironolactone,心力衰竭治疗指南：常规治疗,所有收缩性心力衰竭患者必需应用,ACE,抑制剂，包括无症状性心力衰竭，,LVEF40%ACE inhibitor treated/not treated,Primary outcome for Overall Program:All-cause death,Primary outcome for each trial:CV death or CHF hospitalization,Swedberg K et al.,J Card Fail,.1999;5:276-282.,主要终点:,所有原因死亡率,次级终点:,心血管死亡、心梗或心衰,其他终点:,安全性和耐受性,卡托普利 50,mg tid,(n,=4,909,),缬沙坦 160,mg bid,(n,=,4,909),卡托普利 50,mg tid+,缬沙坦 80,mg bid,(n,=,4,885),急性心梗,(0.510 天,),符合,SAVE,AIRE,或,TRACE,入选标准,(同时具有心衰或左室收缩功能障碍的临床/放射学证据,),主要排除标准,:,血清肌酐 2.5,mg/,dL,血压 100,mm Hg,既往对,ARB,或,ACEI,不耐受,不同意参加研究,双盲活性对照,平均随访时间:24.7 月事件驱动:2,700次事件,VALIANT:,研究设计,0.2,0.4,0.6,0.8,No.of Patients,Favors Valsartan,Favors Placebo,Combined end point,ACE-I y,BB n 3034,ACE-I y,BB y 1610,ACE-I n,BB n 226,ACE-I n,BB y 140,Mortality,ACE-I y,BB n 3034,ACE-I y,BB y 1610,ACE-I n,BB n 226,ACE-I n,BB y 140,1.2,1.4,1.6,1.8,1.0,Val-HeFT:Combined Morbidity/Mortality in Subgroups,BB=,-blocker;y=yes;n=no.,Cohn J et al.,N Engl J Med.,2001;345:1667-1675.,ESC Guidelines on the diagnosis and treatment of CHF,EHJ 2005,对,ACE,抑制剂有不能耐受症状的患者，,ARBs,可以很好的替代,ACE,抑制剂，可以降低发病率和死亡率,(,证据水平,B,I,级),ARBs,和,ACE,抑制剂在治疗,CHF,方面，有相似的功能,(,证据水平,B,I,级),急性心肌梗死后,有心衰 或,左室功能障碍征兆，,ARBs,与,ACE,抑制剂有相似的疗效,(,证据水平,B,I,级),联合使用,ARBs,与,ACE,抑制剂治疗有症状的患者，能够降低死亡率,(,证据水平,B,IIa,级),和心衰的入院治疗率,(,证据水平,A,I,级),The Role of ARBs in Heart Failure,坎地沙坦,4-32,缬沙坦,80-320,依普沙坦,400-800,氯沙坦,50-100,依贝沙坦,150-300,替米沙坦,40-80,通常被用来治疗心衰的,ARBs,可降低死亡率/发病率的,ARB,每日剂量（,mg),ESC Guidelines on the diagnosis and treatment of CHF,EHJ 2005,RAS,抑制,阻滞剂治疗心力衰竭患者：,ACE,抑制剂 或,ARBs,必须先于,阻滞剂？,Stable doses,of diuretics,digoxin,nitrates,Baseline/,screening,Up-titration,Phase A,0,wk,Up-titration,Phase B,Maintenance,Phase,9,18,3,6,12,15,0,Down-titration,Phase,Follow-up(months),CARMEN,研究设计,Group 2,Placebo(blinded),Carvedilol(blinded),Group 1,Carvedilol(blinded),Ealapril(blinded),Enalapril(blinded),Group 3,Enalapril(blinded),Placebo(blinded),CARMEN Primary Endpoint:Comparison of LVESVI Between Treatments,Month 6,Month 12,Month 18,NS,P,3 months,LV function,35%(,40%if LV dilated per echo),90%receiving diuretics,69%ACE-inhibitor,17%angiotensin receptor blocker,74%beta-blocker,A-Heft Trial:Primary Endpoint,Presented at AHA 2004,All individual components of the primary composite endpoint were significantly improved with ISDN-hydralazine therapy,namely death,first hospitalization for heart failure,and change in the quality-of-life score(a larger negative score indicates a better quality of life).,