Table 9

Comparison of major beta blocker trials in heart failure

TrialDrug and target doseEjection fraction criteria (mean)New York Heart Association classNumber of subjectsAnnual placebo mortalityMortality reductionWithdrawal rate for active drug groupa
CIBIS-IIBisoprolol
10mg once daily
<35% (0.27)III (81%)
IV (19%)
264713%34%15%
MERIT-HFMetoprolol
CR 200mg once daily
<40% (0.28)II (41%)
III (56%)
IV (3.6%)
399111%34%14%
BESTBucindolol
100mg twice daily
<35%III-IV270817%10%b23%
COPERNIC
US
Carvedilol
25mg twice daily
<25% (0.20)NR228919%35%12.6%
US
Carvedilolc
Carvedilol
25mg twice dailyd
≤35%II–IV109412%65%e11%f
SENIORS (age ≥ 70 yrs)Nebivolol
10 mg daily
≤35%g (0.36)I 2.85%
II 56.4%
III 38.7%
IV 2.05%
212810%13%b,h26.7%
a

All values were not different from the placebo group except for COPERNICUS (placebo withdrawal rate 15.9%, P=0.0026).

b

Not significant.

c

Planned analysis of pooled results of 4 independent, double-blind placebo-controlled trials.

d

Dosage target was 50 mg twice daily in patients whose weight was 85 kg or more.

e

Mortality was not the primary endpoint, and the estimated mortality reduction was inflated because of the use of an active-drug run-in period before randomization. Withdrawal rates are also affected by use of an active-drug run-in phase. See Table 10.

f

Study stopped early on recommendation of Data and Safety Monitoring Board based on finding of a significant effect of carvedilol on survival. When program was terminated, more patients were receiving or had completed treatment with carvedilol than placebo (89% compared with 83%, P=0.002).

g

The SENIORS trial included patients with at least one of the following: documented hospital admission within previous 12 months with discharge diagnosis of congestive heart failure or documented left ventricular ejection fraction ≤ 35% within the previous 6 months.

h

The composite of all-cause mortality or cardiovascular hospital admission was the primary endpoint and all-cause mortality was measured as a secondary outcome.

All values were not different from the placebo group except for COPERNICUS (placebo withdrawal rate 15.9%, P=0.0026).

Not significant.

Planned analysis of pooled results of 4 independent, double-blind placebo-controlled trials.

Dosage target was 50 mg twice daily in patients whose weight was 85 kg or more.

Mortality was not the primary endpoint, and the estimated mortality reduction was inflated because of the use of an active-drug run-in period before randomization. Withdrawal rates are also affected by use of an active-drug run-in phase. See Table 10.

Study stopped early on recommendation of Data and Safety Monitoring Board based on finding of a significant effect of carvedilol on survival. When program was terminated, more patients were receiving or had completed treatment with carvedilol than placebo (89% compared with 83%, P=0.002).

The SENIORS trial included patients with at least one of the following: documented hospital admission within previous 12 months with discharge diagnosis of congestive heart failure or documented left ventricular ejection fraction ≤ 35% within the previous 6 months.

The composite of all-cause mortality or cardiovascular hospital admission was the primary endpoint and all-cause mortality was measured as a secondary outcome.

From: Results

Cover of Drug Class Review: Beta Adrenergic Blockers
Drug Class Review: Beta Adrenergic Blockers: Final Report Update 4 [Internet].
Helfand M, Peterson K, Christensen V, et al.
Portland (OR): Oregon Health & Science University; 2009 Jul.
Copyright © 2009, Oregon Health & Science University, Portland, Oregon.

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