β受体阻滞剂在慢性心衰中的作用英文幻灯

1会计学受体阻滞剂在慢性心衰中的作用英文幻受体阻滞剂在慢性心衰中的作用英文幻灯灯01020304050607080Mean + SD.Adapted from Bristow. J Am Coll Cardiol. 1993.Normal function (n=12)Cardiomyopathy (n=54)b1b2a1*P.05 vs normal functionReceptor density (fmol/mg protein)*b1:b2 80%:20%b1:b2 65%:35%1981 GMT NORVEGIAN timolol multicenter study1982/1983 SOTALOL trial BHAT The effect of pindolol.1999 CIBIS II MERIT-HF1985 BELFAST metoprolol trial MIAMI1987LIT1990APSI1993 ESVEM CASH MDC1984PREMIS1986ISIS-11975Effect of chronic betaClinical Trials with Beta-BlockersPOST-MI TRIALS HF TRIALS1996US-CHFP1994CIBIS200. BEST COPERNICUS CAPRICORN CARMEN COMET1992Simpaticetomia cardiaca sx e oxprenololo in pz. con IMACIBIS I: Survival in CHF patientswithout a history of MI1008060400200400600800100012001400survival (%)survival time (days)Bisoprolol PlaceboBisoprolol: n = 18 deaths/151 (11.9%)log-rank test p = 0.01Placebo: n = 42 deaths/187 (22.5%)CIBIS Investigators and Committees. Lechat Ph et al. Circulation 1994; 90: 1765177347% reduction47% reductionAll 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 yearsCIBIS IICardiac Insufficiency Bisoprolol Study199934% Time after inclusion (days)1.00.80.600200400600800SurvivalBisoprolol: 156 deaths (n = 1327)Placebo: 228 deaths (n = 1320)log rank test, p .25SOLVD2IIIII8.28.8.25SAVE3I57.291CONSENSUS Trial Study Group. N Engl J Med. 1987;316:14291435.2The SOLVD Investigators. N Engl J Med. 1991;325:293302.3Rutherford JD et al. Circulation. 1994;90:17311738.RiskReduction34%Percent of PatientsMonths of follow-up036912 15182120155010MERIT-HF Study Group. Lancet. 1999;253:20012007.P=.0062 (adjusted)Metoprolol CR/XL(n=1990)Placebo(n=2001)MERIT-HFCIBIS-IIRandomized(No run-in phase)COMET Study Design3029 patients with stable heart failure, New York Heart Association Class II-IV, receiving standard treatment including ACE inhibitors Time to 1020 deathsEstimated to be 4 to 6 yearsScreeningTitration to maximum toleratedor 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 bidPoole-Wilson PA et al. Eur J Heart Fail 2002;4:321-329.Heart rate (beats.min-1)MetoprololCarvedilolTime (years)7075800123456585* *COMET: Change of heart rate* p0.05, * p0.01Error bars represent 1 standard error Time (years)Blood pressure (mm Hg)708090100110120130012345* * * * * * p = 0.05* p = 0.01* p = 0.001 MetoprololCarvedilolSystolicDiastolicDifference at 4 months-1.8 mm Hg, (% CI 3.2 to 0.4Time (years)Percentage Mortality (%)010203040012345Relativerisk95% CIp valueCarvedilol vs Metoprolol0.8280.736, 0.931 0.0017 *CarvedilolMetoprolol17%COMET: Primary endpoint of mortality Sudden DeathCirculatory FailureDeath from strokeTime (years)Mortality (%)COMET: Mode of deathHazard ratio: 0.81 95% CI: 0.677, 0.97p=0.0216Hazard ratio: 0.827 95% CI: 0.673, 1.016p=0.0702Hazard ratio: 0.332 95% CI: 0.177, 0.624p=0.0006051015200123450510152001234501234012345MetoprololCarvedilolCOPERNICUSCarvediloln=1156Placebon=113335% reduction (p=.0014)Number of DeathsEndpoint Data from the SENIORS StudyCleland et al., Eur J Heart Fail 2004;6:787Primary endpoint375 (35.3%)332 (31.1%)0.86 (0.74-0.99) 0.039Mortality192 (18.1%)169 (15.8%)0.88 (0.71-1.08) 0.214Placebo(N=1061)Nebivolol(N=1067)Hazard ratioPProbability of SurvivalP=.01Total Events = 652061218243036420.40.60.81.0BucindololPlaceboP=.27Total Events = 208061218243036420.40.60.81.0BucindololPlaceboNonblacks (n=2081)Blacks (n=627)17%18%The Beta-Blocker Evaluation of Survival Trial Investigators. N Engl J Med. 2001;344:16591667.Months Post-randomizationMonths Post-randomizationCIBIS IIICardiac Insufficiency BIsoprolol StudyBisoprolol o.d.1.252.53.755.07.52.55.010.0 mg10.0 mgStudy designBisoprolol-firstBisoprolol o.d.Enalapril b.i.d.1.252.53.755.07.52.55.010.0 mg10.0 mgBisoprolol o.d. weekStudy end 1 - 2.5 yr16-94 weeks0 2 4 6 8 10 26 28 30 32 34 36* * * * * * * * * * * * * * * * . * * * * *First up-titrationMaintenance periodSecond up-titrationSecond maintenance period 50607080901000612182777638728985386B/E vs E/BHR 0.95 (95% CI 0.76-1.19)P=0.66 (difference)% withouthospitalizations505505mesiPatientsat riskBisoprolol-firstEnalapril-firstPrimary EndpointDOI: 10.1161/CIRCULATIONAHA. 105.582320Per-protocol (PP)5060708090100061218B/E vs E/BHR 0.97 (95% CI 0.78-1.21)non-inferiority P=0.0465034983563532652598073Bisoprolol-firstEnalapril-firstIntention-to-treat (ITT)5060708090100061218B/E vs E/BHR 0.94 (95% CI 0.77-1.16)non-inferiority P=0.0195055053893882912778776Bisoprolol-first was consideredsignificantly non-inferior to enalapril-firstif the upper limit of the 95% CI wasbelow hazard ratio (HR) 1.17 (P.25SOLVD2IIIII8.28.8.25SAVE3I57.291CONSENSUS Trial Study Group. N Engl J Med. 1987;316:14291435.2The SOLVD Investigators. N Engl J Med. 1991;325:293302.3Rutherford JD et al. Circulation. 1994;90:17311738.