Authors' objectives

To summarise the current evidence from randomised controlled trials (RCTs) of diuretics in patients with congestive heart failure (CHF).

Searching

MEDLINE and EMBASE were searched between 1966 and 1999. The keywords were listed in the paper. In addition,, pertinent journals were handsearched and the reference lists of papers were inspected. Book chapters and editorials were also scanned.

Study selection

Assessment of study quality

The authors state that methodological quality was assessed, but they do not report a method for assessing validity. Two reviewers assessed the methodological quality of each paper.

Data extraction

Two reviewers independently abstracted the data using a standardised protocol

Methods of synthesis

Results of the review

Seventeen studies were included in the primary analyses of the review: 7 randomised placebo-controlled trials (n=431) and 10 randomised active-controlled trials (n=383). A further analysis included one additional large study.

Mortality: 3 placebo-controlled trials (n=221) reported data; the OR was 0.25 (95% confidence interval, CI: 0.07, 0.84, P=0.03), representing an absolute risk reduction of 8% in mortality in patients treated with diuretics compared to placebo.

Worsening of heart failure: 4 placebo-controlled trials (n=448) and 4 active-controlled trials (n=177) reported data. The OR was 0.31 (95% CI: 0.15, 0.62, P=0.001) for the placebo-controlled trials and 0.34 (95% CI:0.10, 1.21, P=0.10) for the active-controlled trials.

Exercise capacity: 6 active-controlled trials (n=174) reported data; the OR was 0.37 (95% CI: 0.10, 0.64, P=0.007). It should be noted that this result was reported in the text as an OR, but in the figure as the standardised mean difference. It was not always clear which outcomes were studied. The inclusion of the large excluded study did not alter the direction or statistical significance of the treatment effects.

Authors' conclusions

Compared with active control, diuretics appeared to reduce the risk of worsening disease and improve exercise capacity. The available data from small studies showed that, in CHF, conventional diuretics reduce the risk of death and worsening heart failure in comparison with placebo.

CRD commentary

The review question, inclusion criteria, search strategy and data from the primary studies were clearly presented. However, there was some discrepancy between the numbers of patients included in the review, as reported in the text and in the tables. Only English language trials were searched and so some studies may have been missed. The authors do not appear to have searched for unpublished material. Two authors assessed the quality of the included studies, but the authors do not state how they assessed validity. In addition, validity assessment data were not reported nor used in interpreting the results of the trials. The authors noted that the included population were considerably younger (59 years) than patients with CHF in the population (74 years).

The outcomes that the authors used were not stated clearly, in particular for exercise capacity. The meaning of the results were reported in two different ways in the paper (OR and standardised mean difference) and were not at all clear.

The authors noted several limitations. All the randomised trials were small and there was great variability in the type of intervention, clinical characteristics, assessment of severity, aetiology of heart failure, study duration, concomitant medications, outcome measures and drop-out rates. Methods of masking and the assessment of outcome measures were not reported clearly in many studies. The inclusion of crossover studies was a statistical weakness. There was also heterogeneity in the mechanism of action of loop diuretics and thiazides, and the dose of diuretics. Given these limitations, the results of the review should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors state that the evidence from trials is insufficient to justify widespread use of diuretics to influence clinical outcomes (e.g. to reduce mortality). Despite this, diuretics will continue to be used routinely in the management of CHF for symptom relief.

Research: The authors state that diuretics have not been tested in long-term trials evaluating survival, mainly because of ethical difficulties. The authors state that it is unlikely that diuretics will be the subject of future trials to evaluate effects on clinical outcomes in compensated heart failure, especially in patients stabilised on angiotensin-converting enzyme inhibitors and beta-blockers.

Bibliographic details

Faris R, Flather M, Purcell H, Henein M, Poole-Wilson P, Coats A. Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials. International Journal of Cardiology 2002; 82(2): 149-158. [PubMed: 11853901]

Indexing Status

Subject indexing assigned by NLM

MeSH

Diuretics /therapeutic use; Heart Failure /drug therapy; Humans; Randomized Controlled Trials as Topic

AccessionNumber

12002000848

Database entry date

30/11/2003

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.