Heart failure bisoprolol carvedilol mortality

Table of Contents
Carvedilol, Bisoprolol, and Metoprolol Use in Patients With Coexistent Heart Failure and Chronic
Obstructive Pulmonary Disease.............................................................................................................1
The safety and tolerability of beta blockers in heart failure with reduced ejection fraction: is the
current underutilization of this evidence-based therapy justified?.......................................................2
Clinical inquiry: what is the best beta-blocker for systolic heart failure?..............................................3
Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-
analysis..................................................................................................................................................4

1. Articol original

Carvedilol, Bisoprolol, and Metoprolol Use

in Patients With Coexistent Heart Failure
and Chronic Obstructive Pulmonary
Disease.
Su VY1, Chang YS, Hu YW, Hung MH, Ou SM, Lee FY, Chou KT, Yang KY, Perng DW, Chen TJ, Liu CJ.

Author information

Abstract

Beta (β)-blockers are under-prescribed in patients with heart failure (HF) and concurrent chronic
obstructive pulmonary disease (COPD) due to concerns about adverse pulmonary effects and a
poor understanding of the effects of these drugs. We aimed to evaluate the survival effects of β-
blockers in patients with coexistent HF and COPD. Using the Taiwan National Health Insurance
Research Database, we conducted a nationwide population-based study. Patients with coexistent
HF and COPD diagnosed between 2000 and 2009 were enrolled. Doses of the 3 β-blockers proven
to be beneficial to HF (carvedilol, bisoprolol, and metoprolol) during the study period were
extracted. The primary endpoint was cumulative survival. Patients were followed until December
31, 2009. The study included 11,558 subjects, with a mean follow-up period of 4.07 years. After
adjustment for age, sex, comorbidities, and severity of HF and COPD, bisoprolol use showed a
dose-response survival benefit [low dose: adjusted hazard ratio (HR) = 0.76, 95% confidence
interval (CI) = 0.59-0.97, P = 0.030; high dose: adjusted HR = 0.40, 95% CI = 0.26-0.63, P < 0.001]
compared with nonusers, whereas no survival difference was observed for carvedilol or
metoprolol. Compared with patients with HF alone, this special HF + COPD cohort received
significantly fewer targeted β-blockers (108.8 vs 137.3 defined daily doses (DDDs)/person-year, P < 
0.001) and bisoprolol (57.9 vs 70.8 DDDs/person-year, P < 0.001). In patients with coexisting HF and
COPD, this study demonstrated a dose-response survival benefit of bisoprolol use, but not of
carvedilol or metoprolol use.

Expert Opin Drug Saf. 2015;14(12):1855-63. doi: 10.1517/14740338.2015.1102225. Epub 2015 Oct
21.

2. Articol original

The safety and tolerability of beta blockers

in heart failure with reduced ejection
fraction: is the current underutilization of
this evidence-based therapy justified?
Kiel RG1, Deedwania P2.

Author information

Abstract

INTRODUCTION:

Beta blockers are one of the cornerstones for treatment of Heart Failure with Reduced Ejection
fraction (HFRef), yet their use is often limited by adverse effects, either perceived or real. We
performed a review of available data using PubMed.gov utilizing beta blocker, heart failure, reduced
ejection fraction and safety as key words.

AREAS COVERED:

Several well designed, large scale randomized clinical trials including CIBS-II (bisoprolol), MERIT-HF
(metoprolol succinate), and Copernicus (carvedilol) among others, have been conducted in patients
with HFRef and demonstrated an improvement in cardiac mortality and morbidity. Despite the
preponderance of data supporting the use of beta blockers for patients HFRef, these medications
remain underutilized and/or are often prescribed at lower than recommended dosages. Some of the
reluctance to embrace beta blockade may be attributed to concern on the part of both the patient
and prescriber about the non-cardiac adverse effects of this class of drugs. We have reviewed
several recent reviews and meta-analyses of trials of beta blocker in heart failure which have
conclusively demonstrated their tolerability in the populations studied.

EXPERT OPINION:
In the final section of this paper we provide our opinions regarding initiating and optimizing beta
blocker therapy for patients with HFRef.

KEYWORDS:

CHF; adverse drug effects; beta blockade; beta blockers; congestive heart failure; heart failure with
reduced ejection fraction; medical therapy; safety

3. Referat sistematic

J Fam Pract. 2015 Feb;64(2):122-3.

Clinical inquiry: what is the best beta-

blocker for systolic heart failure?
Hulkower S1, Aiken BA1, Stigleman S1.

Author information

Abstract

Three beta-blockers--carvedilol, metoprolol succinate, and bisoprolol--reduce mortality equally

(by about 30% over one year) in patients with Class III or IV systolic heart failure. Insufficient
evidence exists comparing equipotent doses of these medications head-to-head to recommend
any one over the others.
4. Referat sistematic

Benefits of β blockers in patients with heart

failure and reduced ejection fraction:
network meta-analysis.
Chatterjee S1, Biondi-Zoccai G, Abbate A, D'Ascenzo F, Castagno D, Van Tassell B, Mukherjee D,
Lichstein E.

Author information

Erratum in

• BMJ. 2013;346:f596.

Abstract

OBJECTIVE:

To clarify whether any particular β blocker is superior in patients with heart failure and reduced
ejection fraction or whether the benefits of these agents are mainly due to a class effect.

DESIGN:

Systematic review and network meta-analysis of efficacy of different β blockers in heart failure.

DATA SOURCES:

CINAHL(1982-2011), Cochrane Collaboration Central Register of Controlled Trials (-2011), Embase

(1980-2011), Medline/PubMed (1966-2011), and Web of Science (1965-2011).

STUDY SELECTION:

Randomized trials comparing β blockers with other β blockers or other treatments.

DATA EXTRACTION:

The primary endpoint was all cause death at the longest available follow-up, assessed with odds
ratios and Bayesian random effect 95% credible intervals, with independent extraction by observers.

RESULTS:

21 trials were included, focusing on atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, and
nebivolol. As expected, in the overall analysis, β blockers provided credible mortality benefits in
comparison with placebo or standard treatment after a median of 12 months (odds ratio 0.69, 0.56
to 0.80). However, no obvious differences were found when comparing the different β blockers head
to head for the risk of death, sudden cardiac death, death due to pump failure, or drug
discontinuation. Accordingly, improvements in left ventricular ejection fraction were also similar
irrespective of the individual study drug.

CONCLUSION:

The benefits of β blockers in patients with heart failure with reduced ejection fraction seem to be
mainly due to a class effect, as no statistical evidence from current trials supports the superiority
of any single agent over the others.

Comment in

• ACP Journal Club. Review: in patients with heart failure, β-blockers reduce mortality but do
not differ from each other. [Ann Intern Med. 2013]

• β blockers for heart failure: which works best? [BMJ. 2013]