Abstract
Purpose
In clinical studies, rivaroxaban treatment has been associated with increased incidence
of syncope not related to bleeding, anemia, or stroke. The study objective was to
evaluate the occurrence of dizziness and/or syncope not related to bleeding, anemia,
or stroke in patients treated with direct oral anticoagulants (DOACs).
Methods
A retrospective, observational, comparative study of adult patients diagnosed with
atrial fibrillation and treated with DOACs was conducted using digital retrieval of
medical records. Primary outcomes were an emergency department (ED) visit or hospitalization
due to syncope, fall, or dizziness. Cases related to bleeding, anemia, or stroke were
excluded. Separate examination of a sample of records validated the data.
Findings
Of 6467 eligible patients, 256 (4%) were hospitalized or referred to the ED due to
fall, syncope, or dizziness during a mean observation period of 20.1 months. After
multivariate regression analysis, statistically independent risk factors were found
to be age (hazard ratio [HR] = 1.04, P < 0.0001) and benzodiazepine use (HR = 1.33, P = 0.03). No statistically significant difference was found among the different DOAC
types regarding the primary outcome (apixaban and rivaroxaban HR = 0.97, P = 0.85; dabigatran and rivaroxaban HR = 1.2, P = 0.386).
Implications
The study results failed to confirm the claimed association between the use of a DOAC
and syncopal symptoms unrelated to bleeding, anemia, or stroke in this relatively
large Israeli patient population. Age and benzodiazepine treatment were significant
independent risk factors of these events.
Keywords
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References
- Direct oral anticoagulants: evidence and unresolved issues.Lancet. 2020; 396: 1767-1776
- Direct oral anticoagulants: a quick guide.Eur Cardiol. 2017; 12: 40-45
- Using direct oral anticoagulants in patients with atrial fibrillation: assessment, monitoring and treatment reversal.Eur Cardiol. 2016; 11: 118-122
- Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N Engl J Med. 2011; 365 (2011): 883-891
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 365:981–92.
- Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009; 361: 1139-1151
- Trials of novel oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation.Curr Cardiol Rev. 2014; 10: 297-302
- Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: systematic review and meta-analysis.PLoS One. 2018; 13e0197583
- Comparative effectiveness and safety of direct oral anticoagulants: overview of systematic reviews.Drug Saf. 2019; 42: 1409-1422
- Comparative effectiveness and safety of direct oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis of observational studies.Drug Saf. 2019; 42: 1135-1148
- Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study.Circ J. 2012; 76: 2104-2111
Xarelto® (Rivaroxaban). Australian Product Information. Available online at: https://www.tga.gov.au/sites/default/files/auspar-rivaroxaban-191022-pi.pdf.
Pradaxa - summary of product characteristics (2022). Available online at: https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf.
Eliquis - summary of product characteristics (2022). Available online at: https://www.ema.europa.eu/en/documents/product-information/eliquis-epar-product-information_en.pdf.
- A basic study design for expedited safety signal evaluation based on electronic healthcare data.Pharmacoepidemiol Drug Saf. 2010; 19: 858-868
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383
- Issues in geriatric care: falls.FP Essent. 2018; 468: 18-25
- Medication use and risk of falls among nursing home residents: a retrospective cohort study.Int J Clin Pharm. 2017; 39: 408-415
- Reducing fall risk in the elderly: risk factors and fall prevention, a systematic review.Minerva Med. 2014; 105: 275-281
- Drug-related falls in older patients: implicated drugs, consequences, and possible prevention strategies.Ther Adv Drug Saf. 2013; 4: 147-154
- Risk of falls in chronic kidney disease.J Frailty Sarcopenia Falls. 2017; 2: 33-38
- Falls and cancer.Clin Oncol (R Coll Radiol). 2020; 32: 569-578
- Falling risk in patients with end-stage knee osteoarthritis.Clin Rheumatol. 2021; 40: 3-9
- Glaucoma and quality of life: fall and driving risk.Curr Opin Ophthalmol. 2018; 29: 135-140
- Geriatric pharmacology: an update.Anesthesiol Clin. 2019; 37: 475-492
- Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems.Curr Drug Metab. 2011; 12: 611-620
Council for International Organizations of Medical Sciences (CIOMS) (2010) Practical aspects of signal detection in pharmacovigilance. Report of CIOMS Working Group VIII, Geneva. Available online at: https://cioms.ch/wp-content/uploads/2018/03/WG8-Signal-Detection.pdf.
- Data mining on electronic health record databases for signal detection in pharmacovigilance: which events to monitor?.Pharmacoepidemiol Drug Saf. 2009; 18: 1176-1184
- Postmarketing safety surveillance: where does signal detection using electronic healthcare records fit into the big picture?.Drug Saf. 2013; 36: 183-197
- Comparison of logistic regression versus propensity score when the number of events is low and there are multiple confounders.Am J Epidemiol. 2003; 158: 280-287
- Propensity score methods gave similar results to traditional regression modeling in observational studies: a systematic review.J Clin Epidemiol. 2005; 58: 550-559
Article info
Publication history
Published online: January 16, 2023
Accepted:
December 18,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Elsevier Inc.
