Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants
Abstract
Studies comparing gender-specific outcomes in patients with atrial fibrillation (AF) have reported conflicting results. Gender differences in cerebrovascular accident/systemic embolism (CVA/SE) or major bleeding outcomes with novel oral anticoagulant (NOAC) use are not known. The goal of this analysis was to perform a systematic review and meta-analysis evaluating gender differences in residual risk of CVA/SE and major bleeding outcomes in patients with nonvalvular AF treated with either warfarin or NOAC. Sixty-four randomized studies were identified using keywords "gender," "AF," and "CVA." Using the Preferred Reporting Items for Systemic Reviews and Meta-analysis method, 6 studies met criteria for inclusion in this meta-analysis. CVA/SE and major bleeding outcomes were separately analyzed in cohorts receiving warfarin and NOAC agents, comparing men with women. Women with AF taking warfarin were at a significantly greater residual risk of CVA/SE compared with men (odds ratio 1.279, 95% confidence interval 1.111 to 1.473, Z = -3.428, p = 0.001). No gender difference in residual risk of CVA/SE was noted in patients with AF receiving NOAC agents (odds ratio 1.146, 95% confidence interval 0.97 to 1.354, p = 0.109). Major bleeding was less frequent in women with AF treated with NOAC. In conclusion, women with AF treated with warfarin have a greater residual risk of CVA/SE and an equivalent major bleeding risk, whereas those treated with NOAC agents deemed superior to warfarin are at equivalent residual risk of CVA/SE and less major bleeding risk compared with men. These results suggest an increased net clinical benefit of NOAC agents compared with warfarin in treating women with AF.
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Female AF patients who have additional stroke risk factors, particularly older age, are at greater risk than men of having a stroke, even those anticoagulated with warfarin.
“Female AF patients who have additional stroke risk factors (particularly older age) are also at greater risk than men of having a stroke, 48,49 even those anticoagulated with warfarin 50 (see Chapter 8 for details).”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [50]
Bleeding risk on anticoagulation is similar in both sexes.
“Bleeding risk on anticoagulation is similar in both sexes, 49,50,53 but women appear less likely to receive specialist care and rhythm control therapy, 54 while the outcomes of catheter ablation or AF surgery are comparable to those in men.55,56”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [50]
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
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- Authors
- Pancholy, S. B., Sharma, P. S., Pancholy, D. S., Patel, T. M., Callans, D. J., & Marchlinski, F. E.
- Affiliations
- The Wright Center for Graduate Medical Education (US)
- Smt. N.H.L. Municipal Medical College (IN)
- University of Pennsylvania (US)
- Corresponding author
- Pancholy, Samir B.
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 113
- Issue
- 3
- Pages
- 485-490
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W2110571427
- Cited by
- 204
- References
- 25
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 10 · 2023: 10 · 2022: 18 · 2021: 15 · 2020: 19 · 2019: 17 · 2018: 27 · 2017: 25 · 2016: 22 · 2015: 13 · 2014: 5
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- non-valvular atrial fibrillation, gender differences, direct oral anticoagulants, warfarin, stroke risk, major bleeding, stroke, systemic embolism
- MeSH terms
- Anticoagulants, Atrial Fibrillation, Female, Hemorrhage, Humans, Male, Prognosis, Risk Factors, Sex Factors, Global Health, Incidence, Sex Distribution, Stroke
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