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Meta-Analysis
. 2014 Oct;100(19):1506-10.
doi: 10.1136/heartjnl-2014-305482. Epub 2014 Jun 20.

Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials

Ruairidh I R Martin  1 , Oksana Pogoryelova  2 , Mauro Santibáñez Koref  2 , John P Bourke  3 , M Dawn Teare  4 , Bernard D Keavney  5
Affiliations
Free PMC article
Meta-Analysis

Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials

Ruairidh I R Martin et al. Heart. 2014 Oct.
Free PMC article

Abstract

Objective: To quantify any risk of atrial fibrillation (AF) associated with ivabradine treatment by meta-analysis of clinical trial data.

Methods: Medline, Embase, Web of Knowledge and the Cochrane central register of controlled trials were searched for double-blinded randomised controlled trials of ivabradine with a minimum follow-up period of 4 weeks. For studies where AF data were unpublished, safety data were obtained from the European Medicines Agency (EMeA) website and personal communications. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration. Meta-analyses were performed of relative risk of AF and absolute risk difference of AF per year of treatment. The main outcome measure was incident AF during the follow-up period.

Results: AF data were available from 11 studies: one from the published report, six from the EMeA and four from personal communications. Ivabradine treatment was associated with a relative risk of AF of 1.15 (95% CI 1.07 to 1.24, p=0.0027) among 21 571 patients in the meta-analysis. From this we estimated that the number needed to harm for ivabradine would be 208 (95% CI 122 to 667) per year of treatment.

Conclusions: AF is a substantially more common side effect of ivabradine treatment than one patient in 10 000, the risk presently reported in the product literature. The incidence of AF has not routinely been reported in clinical trials of ivabradine.

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Figures

Figure 1
Figure 1
Flow chart of study selection.
Figure 2
Figure 2
Forest plot of relative risk of atrial fibrillation in all trials with available data. RE Model, random effects model.
Figure 3
Figure 3
Number needed to harm per year of follow-up. Individual studies are plotted as circles with size proportional to the weighting in the meta-analysis model of absolute risk difference. The best fit line with 95% CI (dashed lines) is shown.
Figure 4
Figure 4
Funnel plot of relative risk versus SE. The plot is largely symmetrical, suggesting that there is no publication bias.
See this image and copyright information in PMC

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