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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Prognostic benefit of beta-blockers in patients not receiving ACE-inhibitors

H Krum, SJ Haas, E Eichhorn, J Ghali, E Gilbert, P Lechat, M Packer, E Roecker, P Verkenne, H Wedel, and J Wikstrand.

Review published: 2005.

CRD summary

This poorly reported review aimed to assess the effect of beta-blockers (BBs) on mortality and hospitalisation rates in patients with chronic heart failure, not treated with angiotensin-converting enzyme inhibitors (ACE-I). The authors concluded that BBs and ACE-I have similar benefits, despite the absence of comparative studies. The findings are unlikely to be reliable given the limitations of the review methods.

Authors' objectives

The authors' stated objective was to determine the effect of beta-blockers (BBs) on mortality and heart failure (HF) hospitalisation rate in patients with systolic chronic HF who were not treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARBs). However, the results and conclusions of the review also referred to participants treated with ACE-I or ARB and appeared to relate to the comparison of BBs and ACE-I.

Searching

MEDLINE and EMBASE, as well as abstracts of key cardiology meetings, were searched. No search terms, dates or search strategies were reported. The authors did not report any language restrictions.

Study selection

Study designs of evaluations included in the review

Placebo-controlled trials with more than 200 patients were eligible for inclusion. Studies included in the review assessed between 641 and 3,991 participants; 4 studies each included over 2,200 participants.

Specific interventions included in the review

Studies that compared BB therapy with placebo were eligible for inclusion. The BBs included were bucindolol, bisoprolol, carvedilol and metoprolol (CR or XL).

Participants included in the review

Studies of patients with chronic systolic HF were eligible for inclusion. The majority of the patients included in the review had a New York Heart Association disease classification of class III to IV, and an ejection fraction of less than 35%. Patients who were treated or not treated with an ACE-I or ARB were included in the review; 4.8% of the total included population were not receiving an ACE-I or ARB at baseline.

Outcomes assessed in the review

Studies that reported all-cause mortality and death or HF hospitalisation were eligible for inclusion.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. However, the reviewers contacted study organisers of the included trials to request data (numbers of patients and numbers of events) according to the baseline use of ACE-I or ARB. Relative risks (RRs) with 95% confidence intervals (CIs) were reported.

Methods of synthesis

How were the studies combined?

The studies were grouped according to study duration (up to 90 days and over 90 days) and combined using a fixed-effect model (Mantel-Haenszel). Pooled RRs were reported with 95% CIs. Historical comparisons with pre-BB data were also calculated from raw event data compared with BB data using published methods.

How were differences between studies investigated?

Differences and similarities between the studies were evident from the text and data tables. Statistical heterogeneity was assessed using chi-squared tests.

Results of the review

Six trials (13,370 patients) were included in the review.

All-cause mortality (6 studies).

Patients receiving BBs were less likely to die than those receiving placebo, but this difference did not quite reach statistical significance at the 5% level (RR 0.73, 95% CI: 0.53, 1.02). There was no evidence of statistical heterogeneity (p=0.411).

Among patients who received ACE-I or ARB at baseline, those who received BBs were significantly less likely to die than those who received placebo (RR 0.76, 95% CI: 0.71, 0.83). There was evidence of statistical heterogeneity (p=0.001).

With the exclusion of one trial that investigated bucindolol, the authors found that among patients not receiving ACE-I or ARB at baseline, those who received BBs were less likely to die than those receiving placebo (RR 0.67, 95% CI: 0.43, 1.04); this difference did not quite reach statistical significance at the 5% level (p=0.073). Among patients who received ACE-I or ARB at baseline, those who received BB were significantly less likely to die than those who received placebo (RR 0.67, 95% CI: 0.60, 0.75).

Combined end point of death or HF hospitalisation (3 studies).

Patients receiving BBs were less likely to die than those receiving placebo, but this difference was not statistically significant at the 5% level (RR 0.81, 95% CI: 0.61, 1.08, p=0.148). The result of the test for heterogeneity was not reported.

Among patients who received ACE-I or ARB at baseline, those who received BBs were significantly less likely to die or be hospitalised for HF than those who received placebo (RR 0.78, 95% CI: 0.74, 0.83, p<0.001). The result of the tet for heterogeneity was not reported.

Authors' conclusions

Given the similar benefit of BBs and ACE-I for the treatment of patients with systolic chronic HF, either of these classes of drugs could be used as first-line therapy.

CRD commentary

This review addressed a research question based on one group of patients: patients who were not receiving ACE-I or ARB. However, the review and its conclusions also considered patients who were treated with these drugs, comparing the effects of BBs and ACE-I.

The review's inclusion and exclusion criteria were stated, but no justification was given as to why only studies with over 200 patients were included. The search strategy was not sufficiently described to allow an assessment of its completeness or to enable the reader to replicate the search. There were no apparent attempts to find unpublished studies so the review findings may be subject to publication bias. Whilst the authors did not report any language restrictions, all of the publications appeared to be in English and so language bias may also be an issue. Poor reporting of the review methods made it difficult to assess whether appropriate steps were taken to avoid errors and bias in the study selection and data extraction processes. No validity assessment was performed, thus the robustness of the findings could not be assessed.

The authors assessed heterogeneity and found evidence for both clinical and statistical heterogeneity in some of the pooled analyses; this suggests that pooling may not always have been appropriate. There were also very few participants who were not receiving ACE-I/ARB in comparison with those who were receiving the drugs, which suggests that the robustness of the findings without ACE-I/ARB may be questionable. The authors noted other methodological problems with some of the studies, again questioning the validity of the findings. Given the many limitations of this review, some of which the authors acknowledged, the findings of the review are unlikely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that ACE-I or BBs could be used as first-line treatment for patients with chronic HF. The authors did not include studies that compared ACE-I with BBs.

Research: The authors stated that comparative clinical trials comparing ACE-I with BBs are required.

Bibliographic details

Krum H, Haas S J, Eichhorn E, Ghali J, Gilbert E, Lechat P, Packer M, Roecker E, Verkenne P, Wedel H, Wikstrand J. Prognostic benefit of beta-blockers in patients not receiving ACE-inhibitors. European Heart Journal 2005; 26(20): 2154-2158. [PubMed: 16014644]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adrenergic beta-Antagonists /therapeutic use; Angiotensin-Converting Enzyme Inhibitors /therapeutic use; Cause of Death; Chronic Disease; Heart Failure /drug therapy /mortality; Hospitalization /statistics & numerical data; Humans; Randomized Controlled Trials as Topic; Treatment Outcome

AccessionNumber

12005001347

Database entry date

30/06/2007

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 16014644

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