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Efficacy and Safety of Anticoagulants in Patients with Atrial Fibrillation and History of Falls or Risk of Falls: A Systematic Review and Multilevel Meta-Analysis

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Abstract

Introduction

Atrial fibrillation (AF) is a major cause of stroke. Anticoagulants substantially reduce risk of stroke but are also associated with an increased risk of bleeding. Because of that, many patients do not receive anticoagulants, particularly patients at risk of falls. This systematic review and meta-analysis aims to compare anticoagulant treatment options for the management of atrial fibrillation patients at risk of falls or with a history of falls.

Methods

We conducted a PRISMA systematic review (until March 2022), including studies evaluating safety and efficacy of different anticoagulants (vitamin K antagonist [VKA] versus non-vitamin K antagonist oral anticoagulant [NOAC]). Outcomes were ischemic stroke, major bleeding, intracranial hemorrhage, hemorrhagic stroke, myocardial infarction, gastrointestinal bleeding, cardiovascular and all-cause mortality. A multilevel meta-analysis was conducted adjusting for clustering effects within studies examining more than one effect size.

Results

A total of 919 articles were identified, 848 after removing duplicates. The full text of 155 were screened and 10 articles were retained for final quantitative synthesis. Risk of bias was moderate to serious for the included studies. In meta-analysis, NOACs were associated with superior effectiveness compared with VKA for ischemic stroke/systemic embolism (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.69–0.98; p < 0.05) and safety (HR 0.53, 95% CI 0.40–0.71; p < 0.05) for intracranial hemorrhage. There were no differences in other outcomes.

Conclusion

NOACs were associated with less intracranial hemorrhages and ischemic strokes/systemic embolisms than VKAs in AF patients at risk of falls. These findings suggesting preferred use of NOACs over VKAs have clinical implications for physicians, patients and policy makers.

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Acknowledgements

We would like to acknowledge Donna Burgess and Carolyn Benny, both librarians, for their useful reviews and expert advice.

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Authors and Affiliations

  1. School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool, UK

    Thibaut Galvain

  2. Liverpool Reviews And Implementation Group, Health Data Science, Liverpool Health Partners, University of Liverpool and The Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK

    Ruaraidh Hill

  3. Department of Health Data Science, University of Liverpool, Liverpool, UK

    Sarah Donegan

  4. School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool, UK

    Paulo Lisboa

  5. Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK

    Gregory Y. H. Lip

  6. School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool, UK

    Gabriela Czanner

  7. Faculty of Informatics and Information Technologies, Slovak University of Technology, Bratislava, Slovakia

    Gabriela Czanner

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  1. Thibaut Galvain
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Correspondence to Thibaut Galvain.

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Funding

TG’s PhD education program is funded by Johnson and Johnson Medical. The funder was not involved in the research, nor in any decisions taken by the authors.

Competing interests

TG is an employee of Johnson and Johnson Medical. RH declares a financial, non-personal, non-specific interest, having delivered educational workshops on health economics, medicines management and HTA for cancer specialists supported by unrestricted sponsorship by the pharmaceutical industry and an industry association (March 2019). No fees received personally. Not specific to the topic of the review. GYHL has served as a consultant for Bayer/Janssen, Bristol Myers Squibb (BMS)/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo and as a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi-Sankyo. The other authors report no competing interests (SD, PL and GC).

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Availability of data and materials

Template data collection form, data extracted, analytical code and any other study documents will be available from the corresponding author on reasonable request.

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Authors' contributions

Conceptualization: GYHL, PL, GC, SD, RH and TG; methodology: GYHL, PL, GC, SD, RH and TG; formal analysis: GC and TG; investigation: GYHL, PL, GC, SD, RH and TG; data curation: GC and TG; writing original draft: TG; writing review and editing: GYHL, PL, GC, SD, RH and TG; visualization: TG; final approval: GYHL, PL, GC, SD, RH and TG. All authors read and approved the final version of the manuscript.

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Galvain, T., Hill, R., Donegan, S. et al. Efficacy and Safety of Anticoagulants in Patients with Atrial Fibrillation and History of Falls or Risk of Falls: A Systematic Review and Multilevel Meta-Analysis. Drug Saf 45, 1349–1362 (2022). https://doi.org/10.1007/s40264-022-01231-x

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