Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients: a meta-analysis Nony P, Boissel J P, Lievre M, Leizorovicz A, Haugh M C, Fareh S, Debreyne B
Authors' objectives To examine the influence of phosphodiesterase inhibitors on mortality in patients with overt chronic heart failure.
Searching MEDLINE (search dates unclear), and national and international abstracting publications (over the preceding 5 years) were searched for relevant studies. Experts and pharmaceutical manufacturers were contacted for additional material.
Study selection Study designs of evaluations included in the review Randomised controlled trials (RCTs) were included.
Specific interventions included in the review Treatment with phosphodiesterase inhibitors (amrinone, milrinone, enoximone, indolidan, vesnarinone, pimobendan).
Participants included in the review Patients with overt chronic heart failure (NYHA class II to IV).
Outcomes assessed in the review Mortality was assessed.
How were decisions on the relevance of primary studies made? The authors do not state how the papers were selected for the review, or how many of the authors performed the selection. Reasons for the exclusion of 4 studies are given.
Assessment of study quality Validity was assessed using the following criteria: placebo-controlled, double-blind studies with sample size more than 30; well-defined a priori end points; minimum follow-up of 3 months; and concomitant use of vasodilators, specifically indicated as being allowed or forbidden. The authors do not state how the papers were assessed for validity, or how many of the authors performed the validity assessment.
Data extraction The authors do not state how the data were extracted for the review, or how many of the authors performed the data extraction.
Methods of synthesis How were the studies combined? The studies were combined using various methods of meta-analysis.
How were differences between studies investigated? Tests of heterogeneity were used. Analysis was performed with and without studies using vesnarinone, and was performed separately for trials that either prohibited or allowed the use of additional vasodilators.
Results of the review Page: 1 / 2 Thirteen RCTs involving 2,732 patients were included.
Overall, there is a non significant increase in the odds of mortality of 17%, but significant heterogeneity exists between the outcomes in the different studies. When the 3 trials using vesnarinone were excluded there was a homogeneous statistically-significant increase in mortality of 41% (95% confidence interval, CI: 11, 79). The increase was greater in trials that prohibited additional vasodilator use (increase of 104%, 95% CI: 10, 270) than in those which permitted their use (increase of 33%, 95% CI: 3, 72). The choice of statistical method did not alter the interpretation of the results.
Authors' conclusions With the exception of vesnarinone, phosphodiesterase inhibitors are responsible for an increased mortality rate, compared with placebo, in patients suffering from chronic heart failure. The results do not support the hypothesis that increased mortality is due to additional vasodilator treatment. Experimental and clinical investigations of vesnarinone should be performed to confirm it's efficacy in reducing mortality in chronic heart failure patients.
CRD commentary The study is based on an extensive and rigorous literature search. The overall results are based on randomised comparisons, and are quite convincing. The differences between vesnarinone and the other drugs, and between studies with and without the use of additional vasodilators, are not based on randomised comparisons, and should, therefore, be interpreted with more caution.
Bibliographic details Nony P, Boissel J P, Lievre M, Leizorovicz A, Haugh M C, Fareh S, Debreyne B. Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients: a meta-analysis. European Journal of Clinical Pharmacology 1994; 46(3): 191-196
PubMedID 8070498
Indexing Status Subject indexing assigned by NLM
MeSH Adult; Chronic Disease; Double-Blind Method; Heart Failure /drug therapy /mortality; Humans; Phosphodiesterase Inhibitors /adverse effects /therapeutic use; Randomized Controlled Trials as Topic
AccessionNumber 11994000163
Date bibliographic record published 01/05/1995
Date abstract record published 01/05/1995
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.
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