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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,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Mastertitelformat bearbeiten,Mastertextformat bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,Beta Blockers in CHF,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.,Normal function(n=12),Cardiomyopathy(n=54),b,1,b,2,a,1,*,P,.05 vs normal function,Receptor density(fmol/mg protein),*,b,1,:b,2,80%:20%,b,1,:b,2,65%:35%,Adrenergic Receptors in Normal vs Failing Left Ventricles,Effects of Initiation of BB Therapy,First Generation BB(Propranolol):No Beta adrenergic support,Profound reduction in CO(Reduced LV contractility&increased PVR),Second Generation BB(Metoprolol,Bisoprolol):Selective Beta-1 blockade,Beta-2 support intact+less vasoconstriction.Better tolerated&better perfusion,Third Generation BB(Carvedilol):Additional Alpha blocking action,Afterload reduction,Frequent orthostatic symptoms,Afterload reduction with carvedilol is not long term,British Heart Journal,1975,37:1022-1036,Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy,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,Clinical Trials with Beta-Blockers,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:Survival in CHF patientswithout a history of MI,100,80,60,40,0,200,400,600,800,1000,1200,1400,survival(%),survival time(days),Bisoprolol,Placebo,Bisoprolol:n=18 deaths/151(11.9%),log-rank test,p=0.01,Placebo:n=42 deaths/187(22.5%),CIBIS Investigators and Committees.Lechat Ph et al.Circulation 1994;90:17651773,47%reduction,47%reduction,Initial Carvedilol Trials in the US,MOCHA,PRECISE,Mild Carvedilol,Severe Carvedilol,All trials were prematurely stopped due to marked reduction in mortality,Double-blind,placebo-controlled,randomised trial,2,647 patients included(NYHA III+IV),Bisoprolol,on top of standard therapy(diuretic+ACE inhibitor),FU for 1.3 years,CIBIS IICardiac Insufficiency Bisoprolol Study,1999,34%,Time after inclusion(days),1.0,0.8,0.6,0,0,200,400,600,800,Survival,Bisoprolol:156 deaths(n=1327),Placebo: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,.,Risk,R,eduction,34%,Percent of Patients,Months of follow-up,0,3,6,9,12,15,18,21,20,15,5,0,10,MERIT-HF,:Total Mortality,MERIT-HF Study Group.,Lancet,.1999;253:20012007.,P,=.0062(adjusted),Metoprolol CR/XL,(n=1990),Placebo,(n=2001),MERIT-HF,CIBIS-II,Randomized,(No run-in phase),COMET Study Design,3029 patients with stable heart failure,New York Heart Association Class II-IV,receiving standard treatment including ACE inhibitors,Time to 1020 deaths,Estimated to be 4 to 6 years,Screening,Titration to,maximum,tolerated,or target dose,(Start:carvedilol 3.125 mg bid,metoprolol tartrate 5 mg bid),Assessments every four months,during maintenance phase,(n,1500)Metoprolol 50 mg bid,(n,1500)Carvedilol 25 mg bid,Poole-Wilson PA et al.Eur J Heart Fail 2002;4:321-329.,Heart rate(beats.min,-1,),Metoprolol,Carvedilol,Time(years),70,75,80,0,1,2,3,4,5,65,85,*,*,*,COMET:,Change of heart rate,*p0.05,*p0.01,Error bars represent 1 standard error,Time(years),Blood pressure(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:,Blood pressure,Metoprolol,Carvedilol,Systolic,Diastolic,Difference at 4 months,-1.8 mm Hg,(%CI 3.2 to 0.4,Time(years),Percentage Mortality(%),0,10,20,30,40,0,1,2,3,4,5,Relative,risk,95%CI,p value,Carvedilol vs,Metoprolol,0.828,0.736,0.931,0.0017*,Carvedilol,Metoprolol,17%,COMET:,Primary endpoint of mortality,Sudden Death,Circulatory Failure,Death from stroke,Time(years),Mortality(%),COMET:,Mode of death,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,Metoprolol,Carvedilol,COMET,Trial:Questions Raised,1.Metoprolol IR 50 mg BID is not an effective treatment.,2.Metoprolol IR 50 mg BID does not provide the s
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