Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Table 1. Characteristics and results of 14 trials on the effect of beta-blockers on mortality in heartfailure patients [1].Primary Design Treatment (dose) Mean age Follow-up All-cause mortalityauthor/ (years ± SD) (years) Treated events/ Control events/trial name total events total eventsAnderson RCT Metoprolol 51 ± 3 1.6 5/25 (20.0%) 6/25 (24.0%)(12.5 mg up to 50 mgtwice daily)Engelmeier RCT, Metoprolol 51 ± 8 0.8 1/9 (11.1%) 2/16 (12.5%)double-blind (6.25 mg up to 100 mgonce daily over4–6 weeks)MDC RCT, Metoprolol 49 ± 12 1.5 23/194 (11.8%) 21/189 (11.1%)double-blind (10 mg up to 150 mgover 7 weeks)Fisher RCT, Metoprolol 63 ± 10 0.5 1/25 (4.0%) 2/25 (8.0%)double-blind (6.25 mg up to 50 mgtwice daily)CIBIS RCT, Bisoprolol 60 ± 1 1.9 53/320 (16.6%) 67/321 (20.9%)double-blind (1.25 mg up to 5 mgonce daily over 4 weeks)Bristow RCT, Bucindolol 56 ± 2 0.2 4/105 (3.8%) 2/34 (5.9%)double-blind (12.5 mg, 50 mgand 200 mg)Krum RCT, Carvedilol 56 ± 2 0.3 3/33 (9.1%) 2/16 (12.5%)double-blind (25 mg twice daily)PRECISE RCT, Carvedilol 61 ± 11 0.5 6/133 (4.5%) 11/145 (7.6%)double-blind (25 mg up to 50 mg,twice daily)US Carvedilol RCT, Carvedilol 58 ± 12 0.5 22/696 (3.2%) 31/398 (7.8%)double-blind (6.25 mg up to25–50 mg twice dailyover 2–10 weeks)Carvedilol RCT, Carvedilol b 2/70 (2.9%) 2/35 (5.7%)efficacy a double-blindColucci RCT, Carvedilol 55 ± 11 1 2/232 (0.9%) 5/134 (3.7%)double-blind (12.5 mg up to 50 mgtwice daily over 6 weeks)ANZHFG RCT, Carvedilol 67 c 1.6 20/207 (9.7%) 26/208 (12.5%)double-blind (3.125 mg up to 25 mgtwice daily over2–5 weeks)CIBIS II RCT, Bisoprolol 61 c 1.3 156/1327 (11.8%) 228/1320 (17.3%)double-blind (1.25 mg up to 10 mgover 5 weeks)MERIT-HF RCT, Metoprolol 64 ± 9 1 145/1990 (7.3%) 217/2001 (10.9%)double-blind (12.5 mg up to 200 mg)aCarvedilol efficacy in severe heart failure. Data presented at the Cardiorenal Advisory Panel Meeting of the US Foodand Drug Administration. Protocol 239 (May 2, 1996). b No dose is available for this study. c No SD is available for thisstudy. ANZHFG = Australia–New Zealand Heart Failure Group; CIBIS = Cardiac Insufficiency Bisoprolol Study; CIBIS II =Cardiac Insufficiency Bisoprolol Study II; MDC = Metoprolol in Dilated Cardiomyopathy Trial; MERIT-HF = MetoprololCR/XL (controlled release [AstraZeneca’s Toprol XL]) Randomized Intervention Trial in Heart Failure; PRECISE =Prospective Randomized Evaluation of Carvedilol in Symptoms and Exercise; RCT = randomized controlled trial;SD = standard deviation; US Carvedilol = US Carvedilol Heart Failure Study Group.441