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Warfarin Use Associates with Increased Risk for Stroke in Hemodialysis Patients with Atrial Fibrillation
Open accessAbstract
Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring.
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“Warfarin use was associated either with a neutral or increased risk of stroke in database analyses of patients on dialysis, [419][420][421] including a population-based analysis in Canada (adjusted HR for stroke 1.14; 95% CI 0.78-1.67,adjusted HR for bleeding 1.44; 95% CI 1.13-1.85).422”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [420]
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Navarro‐García, J. A., Keefe, J. A., Song, J., Li, N., & Wehrens, X. H. T. (2025) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2025.06.002 · Cited by 14
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Genovesi, S., & Santoro, A. (2012) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2013.746661 · Cited by 11
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“In a retrospective cohort study of hemodialysis patients with preexisting AF, warfarin use was associated with a significantly increased risk for stroke compared with nonuse.(41) In a meta-analysis of patients with AF and nondialytic CKD, the use of warfarin had a neutral effect on the risk of stroke and mortality, bu…”
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“Studies done during the last quarter of previous century as well as those during the early years of present century reported that chronic anticoagulation in these patients was associated with increased risk of CVA [3,21,34], while studies done more recently report more favorable outcome with anticoagulation in these p…”
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Oral anticoagulation for stroke prevention in atrial fibrillation and advanced kidney disease
Ballegaard, E. L. F., Olesen, J. B., Kamper, A., Feldt‐Rasmussen, B., Gislason, G., Torp-Pedersen, C. T., & Carlson, N. (2024) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2024.102350 · Cited by 8
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“[30] analyzed the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) wave II for patients hospitalized for atrial fibrillation between 1996 and 2000.”
BackgroundMethodAtrial Fibrillation in Patients with Chronic Kidney Disease
Kotalczyk, A., Ding, W. Y., Wong, C. F., Rao, A., Gupta, D., & Lip, G. Y. H. (2021) · Cardiology Clinics · doi:10.1016/j.ccl.2021.04.005 · Cited by 8
Slaughter, M. S., Pederson, B. D., Graham, J. D., Sobieski, M. A., & Koenig, S. C. (2011) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2011.01.012 · Cited by 7
Bhatia, H. S., Bailey, J., Ünlü, O., Hoffman, K., & Kim, R. J. (2019) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.13811 · Cited by 6
Time in Therapeutic Range for Dialysis Patients on Warfarin
Niznik, R. S., Hoel, R. W., Vaughan, L. E., Majorowicz, R. R., & Albright, R. C. (2020) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.02.030 · Cited by 6
Barcía, J. A. P., Raposeiras‐Roubín, S., Abu-Assi, E., Erquicia, P. D., Castro, A. L., Lestón, L. R., Míguez, J. O., Bermúdez, I. G., & Íñiguez, A. (2023) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.03.018 · Cited by 7
Still unresolved: warfarin in ESRD with atrial fibrillation
Winkelmayer, W. C. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.48 · Cited by 6
Atrial Fibrillation in Dialysis Patients: Time to Abandon Warfarin?
Brancaccio, D., Neri, L., Bellocchio, F., Barbieri, C., Amato, C., Mari, F., Canaud, B., & Stuard, S. (2016) · The International Journal of Artificial Organs · doi:10.5301/ijao.5000487 · Cited by 6
“However, a more recent contribution from Chan et al (48) is discouraging the use of dabigatran and rivaroxaban in dialysis patients with AF.”
BackgroundResultInfluentialKılıçkap, M., Bosch, J., Eikelboom, J. W., & Hart, R. G. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.06.003 · Cited by 6
Diagnosis and Treatment of Pulmonary Embolism in Challenging Populations
Werth, S., & Beyer‐Westendorf, J. (2018) · Hämostaseologie · doi:10.1055/s-0038-1641586 · Cited by 6
“Potential explanations for a higher incidence of thromboembolic and bleeding complications may include: (cid:129) More unstable INR courses with a higher risk of overdose, which increases the risk of bleeding in CKD. 72 (cid:129) Higher age and more complex co-morbidities of CKD patients.”
InfluentialVitamin K antagonist use and renal function in pre-dialysis patients
Voskamp, P. W. M., Dekker, F. W., Rookmaaker, M. B., Verhaar, M. C., Bos, W. J. W., van Diepen, M., & Ocak, G. (2018) · Clinical Epidemiology · doi:10.2147/clep.s154719 · Cited by 6
“12 –9,13 with the exception of two Therefore, the aim of this study was to investigate the association between vitamin K antagonist use and the rate of kidney function decline and time until start of dialysis in incident pre-dialysis patients.”
Atrial Fibrillation and Oral Anticoagulation in Chronic Kidney Disease.
Engelbertz, C. M., & Reinecke, H. (2012) · Europe PMC (PubMed Central) · doi:10.4022/jafib.445 · Cited by 6
Atrial Fibrillation and Chronic Kidney Disease
Schlieper, G., Krüger, T., & Floege, J. (2012) · New England Journal of Medicine · doi:10.1056/nejmc1212362 · Cited by 6
Roh, J., Kim, Y., Kim, D., Park, S., Park, K., Kim, M., Hwang, K. W., Hwang, W., Park, G., & Lee, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-65541-z · Cited by 6
Fibrilación auricular no valvular en pacientes en hemodiálisis crónica. ¿Debemos anticoagular?
González, S., & Calvo, J. A. H. (2022) · Nefrología · doi:10.1016/j.nefro.2022.01.005 · Cited by 6
Yalamanchili, V., & Reilly, R. F. (2011) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2011.00885.x · Cited by 5
“In an analysis of 48,825 incident hemodialysis patients for each one-point increase in CHADS2 score, risk of new stroke was increased 27%, a value similar to that in the general population (6).”
BackgroundThet, Z., & Vilayur, E. (2013) · Nephrology · doi:10.1111/nep.12057 · Cited by 5
“On the contrary, a large (1671 patients, 30% warfarin use) retrospective study showed that warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization.(23) Chan et al.”
BackgroundL’éveil de la matrix-gla-protéine sonnera le glas des calcifications vasculaires
Delanaye, P., Liabeuf, S., Bouquegneau, A., Cavalier, E., & Massy, Z. A. (2015) · Néphrologie & Thérapeutique · doi:10.1016/j.nephro.2014.12.003 · Cited by 5
Oral Anticoagulant Therapy in Patients Receiving Haemodialysis: Is It Time to Abandon It?
Saracyn, M., Brodowska-Kania, D. A., & Niemczyk, S. (2013) · The Scientific World JOURNAL · doi:10.1155/2013/170576 · Cited by 5
“It is also difficult to perform a reliable meta-analysis, because the individual studies sometimes differ in their design, specific assumptions, methods of collecting data, ormethods of analysis [37, 38, 53].”
BackgroundMethodCho, M. S., Choi, H. O., Hwang, K. W., Kim, J., Nam, G., & Choi, K. (2023) · BMC Cardiovascular Disorders · doi:10.1186/s12872-023-03236-5 · Cited by 7
ENFERMEDAD CARDIOVASCULAR (ECV) EN LA ENFERMEDAD RENAL CRÓNICA (ERC)
Rodrigo Orozco, B. (2015) · Revista Médica Clínica Las Condes · doi:10.1016/j.rmclc.2015.04.003 · Cited by 5
“Otra observación sorprendente fue la de la terapia anticoagulante en pacientes con fibrilación auricular y ERC, dónde la warfarina no reducía el riesgo de accidente vascular encefálico, sino que lo aumentaba (46).”
BackgroundDaimon, S. (2018) · Therapeutic apheresis and dialysis · doi:10.1111/1744-9987.12744 · Cited by 3
Heparin Use in Hemodialysis Patients following Gastrointestinal Bleeding
Shen, J. I., Mitani, A., & Winkelmayer, W. C. (2014) · American Journal of Nephrology · doi:10.1159/000367901 · Cited by 5
Abe, M., Maruyama, N., Suzuki, H., Okada, K., & Soma, M. (2012) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31826f34f3 · Cited by 5
Challenging the use of warfarin in patients on dialysis with atrial fibrillation
Schlieper, G., & Floege, J. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.87 · Cited by 5
Langenhuijsen, L. F. S., Derksen, D. C. L., Milders, J., van der Horst, S. F. B., van Diepen, M., Trines, S. A. I. P., den Exter, P. L., Klok, F. A., Rotmans, J. I., & de Jong, Y. (2025) · Kidney Medicine · doi:10.1016/j.xkme.2025.101200 · Cited by 5
Martínez-Arango, J. M., Rojas-Echavarría, L. M., Garcia-Mejía, C., Castrillón-Spitia, J. D., & Higuita-Gutiérrez, L. F. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15072641 · Cited by 4
Metadata
- Authors
- Chan, K. E., Lazarus, J. M., Thadhani, R., & Hakim, R. M.
- Affiliations
- Fresenius Medical Care (United States) (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Chan, Kevin E.
- Lazarus, J. Michael
- Hakim, Raymond M.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2009-10
- Volume
- 20
- Issue
- 10
- Pages
- 2223-2233
- ISSN
- 1046-6673 (ISSN-L)
- PMC
- PMC2754104
- OpenAlex
- W2137138584
- Cited by
- 431
- References
- 86
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 17 · 2022: 15 · 2021: 20 · 2020: 23 · 2019: 21 · 2018: 38 · 2017: 40 · 2016: 40 · 2015: 43 · 2014: 34 · 2013: 35 · 2012: 29
- FWCI
- 16.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Keywords
- warfarin, stroke risk, hemodialysis, atrial fibrillation, end-stage renal disease, clopidogrel, aspirin, INR monitoring, anticoagulation, mortality, hospitalization
- MeSH terms
- Aged, Anticoagulants, Atrial Fibrillation, Female, Renal Dialysis, Hospitalization, Humans, Kidney Failure, Chronic, Male, Regression Analysis, Retrospective Studies, Risk, Warfarin, Cohort Studies, International Normalized Ratio, Stroke
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