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Meta-Analysis
. 2009 Sep 21:10:113.
doi: 10.1186/1471-2474-10-113.

Bisphosphonates and atrial fibrillation: Bayesian meta-analyses of randomized controlled trials and observational studies

Anselm Mak  1 , Mike W L Cheung, Roger Chun-Man Ho, Alicia Ai-Cia Cheak, Chak Sing Lau
Affiliations
Meta-Analysis

Bisphosphonates and atrial fibrillation: Bayesian meta-analyses of randomized controlled trials and observational studies

Anselm Mak et al. BMC Musculoskelet Disord. .

Abstract

Background: Occurrence of atrial fibrillation (AF) amongst bisphosphonate users has been increasingly reported but results are conflicting. We performed a Bayesian meta-analysis to address the possible association between the occurrence of AF and bisphosphonate use and estimated the posterior probability of development of AF with bisphosphonate use.

Methods: Randomized controlled trials (RCTs) evaluating the efficacy and safety of bisphosphonates for treating and preventing osteoporosis, and observational studies investigating the incidence of AF amongst bisphosphonate users, were searched in electronic databases. We pooled the effect size with Bayesian meta-analysis for odds ratio (OR) and calculated its posterior probability of development of AF in bisphosphonate users for RCTs and observational studies, reported with the 95% credible interval (CI).

Results: Of 1751 potentially relevant citations initially retrieved, 4 RCTs and 2 reports of RCTs, and 3 observational studies were included for this meta-analysis. On pooling the RCTs, there was a non-significantly higher risk of overall (OR 1.184, 95% CI 0.837-1.656) and serious AF (OR 1.590, 95% CI 0.613-3.751) in bisphosphonate-treated patients. Combining data of observational studies also revealed a non-significantly higher risk of AF in bisphosphonate users (OR 1.251, 95% CI 0.980-1.732). Using Bayesian meta-analysis based on the effect size of observational studies as the prior, the posterior probability of OR>1.2 in the development of AF amongst bisphosphonate users in the RCTs was 0.484. Egger's regression demonstrated no notable publication bias in all the analyses.

Conclusion: The current meta-analysis revealed no evidence of a higher risk of AF associated with bisphosphonate use. Nevertheless, based on Bayesian meta-analysis with the effect size of the observational studies as the prior, the posterior probabilities of development of AF was found to be 0.484 if the risk of AF was estimated to be more than 20%. The results of the current meta-analysis thus offer clinicians the practical probability of development of AF in patients who take bisphosphonates for the treatment of bone loss and corticosteroid induced osteoporosis.

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Figures

Figure 1
Figure 1
Summary of the literature search.
Figure 2
Figure 2
Forest plot of the odds ratio of atrial fibrillation: Bisphosphonate users versus controls by pooling *4 RCTs. Abbreviations: RCT, randomized control trial; BP, bisphosphonate; AF, atrial fibrillation; CI, credible interval; RE, random effects. *Two RCTs in Cummings et al's study. See text for details.
Figure 3
Figure 3
Forest plot of odds ratio of serious atrial fibrillation: Bisphosphonate users versus controls by pooling *4 RCTs. Abbreviations: RCT, randomized control trial; BP, bisphosphonate; AF, atrial fibrillation; CI, credible interval; RE, random effects. * Two RCTs in Cummings et al's study. See text for details.
Figure 4
Figure 4
Forest plot of the odds ratio of atrial fibrillation: Bisphosphonate users versus non-bisphosphonate users by pooling 3 observational studies. Abbreviations: BP, bisphosphonate; AF, atrial fibrillation; CI, credible interval; RE, random effects.
Figure 5
Figure 5
Forest plot of the odds ratio of atrial fibrillation: Bisphosphonate users versus controls by pooling *4 RCTs and **2 reports of RCTs. Abbreviations: RCT, randomized control trial; BP, bisphosphonate; AF, atrial fibrillation; CI, credible interval; RE, random effects. * Two RCTs in Cummings et al's study. **Karam 2007 and Papapoulous 2008 are 2 reports of RCTs. See text for details
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