Authors' objectives

To determine the effect of angiotensin-receptor blockers (ARBs) on mortality and hospitalisation in patients with heart failure.

Searching

MEDLINE, EMBASE, Biological Abstracts, International Pharmaceutical Abstracts, Cochrane Controlled Trials Register, the Cardiovascular Randomized Clinical Trial (CVRCT) Registry, and the Science Citation Index were searched. The search dates covered 1966 to 2001 and the keywords were reported. Studies not published in full in peer-reviewed journals were excluded from the review.

Study selection

Assessment of study quality

Study quality was assessed by the adequacy of randomisation, blinding, and descriptions of withdrawals and drop-outs. It appears that two reviewers independently assessed study quality.

Data extraction

Two reviewers independently extracted the data and any disagreements were resolved through consensus or a third reviewer. Investigators were contacted for missing information. Outcomes data were extracted to calculate the odds ratios (ORs) by intention-to-treat.

Methods of synthesis

Results of the review

Seventeen RCTs (n=12,469) were included.

When all the studies were pooled no difference was shown in all-cause mortality (OR 0.96, 95% CI: 0.75, 1.23). There was no difference in hospitalisation for heart failure based on 6 trials (OR 0.86, 95% CI: 0.69, 1.06). Statistical heterogeneity was of borderline significance in both of these analyses. There was a non-statistically significant trend towards lower mortality with ARBs versus placebo based on 7 trials (OR 0.68, 95% CI: 0.38, 1.22), but no difference between ARBs and ACEIs or between ARB-ACEI combination therapy and ACEIs. Only one large trial showed a statistically significant reduction in hospitalisation; this favoured the ARB-ACEI combination over ACEI. The sensitivity analyses excluding ACEI-intolerant patients and studies of less than 6 months did not change the findings. The funnel plot did not suggest the presence of publication bias.

Authors' conclusions

The authors concluded that in patients with symptomatic heart failure the results could not confirm that ARBs are better for reducing all-cause mortality or hospitalisation for heart failure, particularly compared to ACEIs.

CRD commentary

The review addressed a well-defined question. However, the restriction to peer-reviewed journal publications does not provide reassurance that all relevant data were included. The authors did attempt to minimise bias and errors in reviewing the studies selected for inclusion. The quality assessment appears to have been hindered by insufficient information on the primary studies, and to have led to an unproven assumption of adequate quality on the basis that the majority of the studies were multicentre trials. The characteristics of the individual studies, apart from quality, were presented clearly. Pooling appears to have been appropriate statistically, the contribution of individual trials to the pooled results was clear, and potential sources of heterogeneity were explored. The authors' conclusions were consistent with the strength of the evidence shown.

Implications of the review for practice and research

Practice: The authors stated that ARB monotherapy and ARB-ACEIcombination therapy appear promising. However, evidence-based guidelines should continue to emphasise ACEIs as the primary therapy, although ARBs may be a reasonable substitute if ACEIs cannot be given.

Research: The authors stated that ongoing trials should helpto determine the role of ARBs in the treatment of heart failure. Three ongoing trials were named in the report: CHARM, OPTIMAL and VALIANT.

Bibliographic details

Jong P, Demers C, McKelvie R S, Liu P P. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. Journal of the American College of Cardiology 2002; 39(3): 463-470. [PubMed: 11823085]

Original Paper URL

http://content.onlinejacc.org/cgi/content/full/39/3/463

Other publications of related interest

Jong, P, Demers C, McKelvie R, Liu P. Angiotensin receptorblockers for heart failure (Protocol for a Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley Sons, Ltd.

Indexing Status

Subject indexing assigned by NLM

MeSH

Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors /therapeutic use; Cardiovascular Agents /therapeutic use; Heart Failure /complications /drug therapy /mortality; Humans; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left /complications /drug therapy

AccessionNumber

12002000443

Database entry date

31/07/2004

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.