Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials
Open accessAbstract
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 For studies where AF data were unpublished, safety data were obtained from the European Medicines Agency (EMeA) website and personal communications.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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Ivabradine increases the risk of atrial fibrillation.
“the 'funny channel blocker' ivabradine, which is used for angina and heart failure, increases the risk of AF. 685”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [685]
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- Authors
- Martin, R. I. R., Pogoryelova, O., Koref, M. S., Bourke, J. P., Teare, M. D., & Keavney, B. D.
- Affiliations
- Freeman Hospital (GB)
- Newcastle University (GB)
- Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
- University of Sheffield (GB)
- University of Manchester (GB)
- Corresponding author
- Martin, Ruairidh I R
- Venue
- Heart
- Publisher
- BMJ
- Published
- 2014-06-20
- Volume
- 100
- Issue
- 19
- Pages
- 1506-1510
- ISSN
- 1355-6037 (ISSN-L)
- 1468-201X
- PMC
- PMC4174120
- OpenAlex
- W2159461724
- Cited by
- 161
- References
- 27
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 9 · 2023: 6 · 2022: 16 · 2021: 16 · 2020: 11 · 2019: 11 · 2018: 14 · 2017: 17 · 2016: 32 · 2015: 13 · 2014: 3
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Heart (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
- Funders
- British Heart Foundation (FS/12/55/29695)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- ivabradine, atrial fibrillation, drug-induced arrhythmia, adverse drug reactions, number needed to harm, atrial fibrillation incidence, drug safety
- MeSH terms
- Ivabradine, Angina Pectoris, Atrial Fibrillation, Benzazepines, Heart Failure, Humans, Incidence, Randomized Controlled Trials as Topic, Risk Assessment
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