β受体阻滞剂在CHF治疗中的作用-课件幻灯

Fare clic per modificare lo stile del titolo dello schema,Fare clic per modificare gli stili del testo dello schema,Secondo livello,Terzo livello,Quarto livello,Quinto livello,*,B,受体阻滞剂在,CHF,治疗中的作用,AJIT BHAGWAT,MD,DM,FACC,FISE,FCSI,FSCAI,Diplomate,American Board of Cardiology,Kamalnayan Bajaj Hospital,Aurangabad,INDIA,0,10,20,30,40,50,60,70,80,Mean+SD.,Adapted from Bristow.J Am Coll Cardiol.1993.,功能正常,(n=12),心脏病,(n=54),b,1,b,2,a,1,*,P,.05 vs,功能正常,受体密度,(fmol/mg protein),*,b,1,:b,2,80%:20%,b,1,:b,2,65%:35%,心功能正常与左心功能下降两组肾上腺受体分布,B,受体阻滞剂治疗的启示作用,第一代,B,受体阻滞剂,(,普奈洛尔,):,无肾上腺受体选择性,第二代,B,受体阻滞剂,(,美托洛尔,比索洛尔,):,高,Beta-1,选择性,，较少,Beta-2,作用,+,较低的血管收缩作用,.,良好的耐受性,&,更好的灌注,第三代B受体阻滞剂(卡维地洛):阻断a受体,降低后负荷,减少体位性病症的发生,卡维地洛对a受体的阻滞并不是长期的,British Heart Journal,1975,37:1022-1036,在充血性心力衰竭治疗上,B,受体阻滞剂的作用,F.Waagstein,A.Hjalmarson,E.Varnauskas,and I.Wallentin,From the Department of Medicine I,Division of Cardiology and Department of Clinical Physiology,Sahlgrens,Hospital,University of Gteborg,Sweden,1981,GMT,NORVEGIAN,timolol,multicenter,study,1982/1983,SOTALOL trial,BHAT,The,effect,of,pindolol,.,1999,CIBIS II,MERIT-HF,1985,BELFAST,metoprolol,trial,MIAMI,1987,LIT,1990,APSI,1993,ESVEM,CASH,MDC,1984,PREMIS,1986,ISIS-1,1975,Effect of chronic beta,使用,B,受体阻滞剂的临床实验,POST-MI TRIALS,HF TRIALS,1996,US-CHFP,1994,CIBIS,200.,BEST,COPERNICUS,CAPRICORN,CARMEN,COMET,1992,Simpaticetomia cardiaca sx,e oxprenololo in pz.con IMA,CIBIS I:,CHF,患者的生存率,无心梗的发病史,100,80,60,40,0,200,400,600,800,1000,1200,1400,生存率,(%),生存时间,(days),比索洛尔,抚慰剂,比索洛尔,:n=18 deaths/151(11.9%),log-rank test,p=0.01,抚慰剂:n=42 deaths/187(22.5%),CIBIS Investigators and Committees.Lechat Ph et al.Circulation 1994;90:17651773,47%reduction,降低,47%,在美国最早的卡维地洛实验,MOCHA,PRECISE,Mild Carvedilol,Severe Carvedilol,所有的实验提前终止是因为死亡率可以明显的降低,双盲,抚慰剂对照,随机,2,647 名患者,心功能分级(NYHA III+IV),在标准治疗的根底上使用比索洛尔(利尿剂+ACEI),随访1.3年,CIBIS II,心功能不全比索洛尔研究,1999,34%,Time after inclusion(days),1.0,0.8,0.6,0,0,200,400,600,800,生存率,比索洛尔,:156 deaths(n=1327),安慰剂,:228 deaths(n=1320),log rank test,p.25,SOLVD,2,IIIII,8.2,8.8,.25,SAVE,3,I,5,7,.29,1,CONSENSUS Trial Study Group.,N Engl J Med,.1987;316:14291435.,2,The SOLVD Investigators.,N Engl J Med,.1991;325:293302.,3,Rutherford JD et al.,Circulation,.1994;90:17311738,.,下降,34%,患者的百分比,时间,0,3,6,9,12,15,18,21,20,15,5,0,10,MERIT-HF,:,总死亡率,MERIT-HF Study Group.,Lancet,.1999;253:20012007.,P,=.0062(adjusted),美托洛尔,(n=1990),抚慰剂,(n=2001),MERIT-HF,CIBIS-II,随机,(,临床导入期,),COMET,研究设计,3029例 稳定心衰HF患者,纽约心脏病学会 Class II-IV,接受包括ACEI在内的标准治疗,1020,例死亡,预计,4,6,年,筛查,逐步增加到,最大耐受剂量,/,靶剂量,(,起始,:,卡维地洛,3.125 mg bid,酒石酸美托洛尔,5 mg bid),维持阶段每,4,个月进行评估,(n,1500),美托洛尔,50 mg bid,(n,1500),卡维地洛,25 mg bid,Poole-Wilson PA et al.Eur J Heart Fail 2002;4:321-329.,心率,(beats.min,-1,),美托洛尔,卡维地洛,时间,(,年,),70,75,80,0,1,2,3,4,5,65,85,*,*,*,COMET:,心率变化,*p0.05,*p0.01,Error bars represent 1 standard error,时间,(,年,),血压,(mm Hg),70,80,90,100,110,120,130,0,1,2,3,4,5,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*p=0.05,*p=0.01,*p=0.001,COMET:,血压变化,美托洛尔,卡维地洛,收缩压,舒张压,四个月时的差异,-1.8 mm Hg,(%CI 3.2 to 0.4,Time(years),死亡率,(%),0,10,20,30,40,0,1,2,3,4,5,Relative,risk,95%CI,p value,卡维地洛,vs,美托洛尔,0.828,0.736,0.931,0.0017*,卡维地洛,美托洛尔,17%,COMET:,首要研究终点 死亡率,猝死,循环衰竭,中风,时间,(,年,),死亡率,(%),COMET:,死亡类型,Hazard ratio:0.81,95%CI:0.677,0.97,p=0.0216,Hazard ratio:0.827,95%CI:0.673,1.016,p=0.0702,Hazard ratio:0.332,95%CI:0.177,0.624,p=0.0006,0,5,10,15,20,0,1,2,3,4,5,0,5,10,15,20,0,1,2,3,4,5,0,1,2,3,4,0,1,2,3,4,5,美托洛尔,卡维地洛,COMET,Trial:,引起的问题,1.,美托洛尔,IR,50 mg BID,不是有效的治疗手段,美托洛尔,IR 50 mg BID,不如,b,1,受体阻滞剂卡维地洛,25mg BID,同样有效,美托洛尔,IR 50 mg BID,不如美托洛尔,XL,有效,.,COPERNICUS,卡维地洛对于严重心衰存活率的影响,哥白尼实验,:,死亡率,卡维地洛,n=1156,抚慰剂,n=1133,下降,35(p=.0014),死亡数,临床获益,三个月内改善LVEF,逆转LV重塑质量&形状：4-12月,生存率获益,降低SCD,降低住院率,SENIORS,研究终点,Cleland et al.,Eur J Heart Fail 2004;6:787,首要终点,375(35.3%),332(31.1%),0.86(0.74-0.99),0.039,死亡率,192(18.1%),169(15.8%),0.88(0.71-1.08),0.214,安慰剂,(N=1061),奈必洛尔,(N=1067),风险比,HR,P,存活率,P,=.01,Total Events=652,0,6,12,18,24,30,36,42,0.4,0.6,0.8,1.0,布新洛尔,抚慰剂,P,=.27,Total Events=208,0,6,12,18,24,30,36,42,0.4,0.6,0.8,1.0,布新洛尔,抚慰剂,非黑人,(n=2081),黑人,(n=627),17%,18%,BEST,:,不同种族,全因死亡率,The,Beta,-Blocker Evaluation of Survival Trial Investigators.N Engl J Med.2001;344:16591667.,随机分组后时间,随机分组后时间,CIBIS III,比索洛尔,心功能不全研究,CIBIS III:,设想？,对于慢性心衰患者CHF，采用1选择性受体阻滞剂比索洛尔进行初始治疗后加用ACEI与先采用ACEI依那普利后加用比索洛尔是同样有效和平安的。,CIBIS III,研究终点,首要终点,研究期末的全因死亡率和全因住院率的联合终点,次要终点,(,选择性的,),研究期末单药阶段期末首要终点的独立因素,单药治疗期末的联合首要终点,初始依那普利,(b.i.d.),比索洛尔,o.d.,依那普利,1.25,2.5,3.75,5.0,7.5,2.5,5.0,10.0 mg,10.0 mg,研究设计,初始比索洛尔,比索洛尔,o.d,.,依那普利,b.i.d.,1.25,2.5,3.75,5.0,7.5,2.5,5.0,10.0 mg,10.0 mg,比索洛尔,o.d,.,依那普利,周,Study end,1-2.5,年,16-94 weeks,0 2 4 6 8 10,26 28 30 32 34 36,*.*,初始加量阶段,维持期,第二期加量阶段,第二期维持阶段,整体研究阶段的全因住院率,(ITT),50,60,70,80,90,100,0,6,12,18,277,76,387,289,85,386,B/E vs E/B,HR 0.95(95%CI 0.76-1.19),P=0.66(difference),%,未住院百分比,505,505,mesi,风险例数,初始比索洛尔,初始依那普利,首要终点,DOI:10.1161/CIRCULATIONAHA.105.582320,方案治疗分析,(PP),50,60,70,80,90,100,0,6,12,18,B/E vs E/B,HR 0.97(95%CI 0.78-1.21),non-inferiority P=0.046,503,498,356,353,265,259,80,73,初始比索洛尔,初始依那普利,意向治疗分析,(ITT),50,60,70,80,90,10