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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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“However, this was dependent on INR-monitoring, as patients without an adequate INR monitoring during the first 90 days after treatment initiation had significantly increased risk for strokes as compared to patients without warfarin treatment.(22) Another report from the Dialysis Outcomes and Practice Patterns Study da…”
Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction
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ResultAnticoagulants in atrial fibrillation patients with chronic kidney disease
Hart, R. G., Eikelboom, J. W., Ingram, A. J., & Herzog, C. A. (2012) · Nature Reviews Nephrology · doi:10.1038/nrneph.2012.160 · Cited by 75
Risks of Death and Stroke in Patients Undergoing Hemodialysis With New-Onset Atrial Fibrillation
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“However, we need to acknowledge that the efficacy of warfarin treatment for stroke prevention in dialysis patients with AF is beyond the scope of the present study because of unavailable information about warfarin use in our claims database, such as adherence to prescribed warfarin and therapeutic values of internatio…”
BackgroundRisk Factors of Ischemic Stroke and Subsequent Outcome in Patients Receiving Hemodialysis
Findlay, M., Thomson, P. C., Fulton, R. L., Solbu, M. D., Jardine, A. G., Patel, R. K., Stevens, K. K., Geddes, C., Dawson, J., & Mark, P. B. (2015) · Stroke · doi:10.1161/strokeaha.115.009095 · Cited by 75
Ischaemic stroke in incident dialysis patients
Sánchez-Perales, C., Vázquez, E., Garcı́a-Cortes, M. J., Borrego, J., Polaina, M., Gutierrez, C. P., Lozano, C., & Liébana, A. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq220 · Cited by 73
“the relationship between ischaemic stroke and AF in the dialysis population is invaluable in establishing indications for anti-thrombotic treatment in this population; albeit, the risk associated with this therapy in the dialysis population has not as yet been sufficiently clarified [28–33].”
BackgroundStroke in patients with chronic kidney disease…: How do we approach and manage it?
Nayak‐Rao, S., & Shenoy, M. P. (2017) · Indian Journal of Nephrology · doi:10.4103/0971-4065.202405 · Cited by 74
“In a retrospective cohort study[16] of incident ESRD patients with co‐existing AF, warfarin use was associated with an increased risk of stroke presumably hemorrhagic stroke even after controlling for potential confounders.”
BackgroundAnticoagulation in Chronic Hemodialysis: Progress Toward an Optimal Approach
Kessler, M., Moureau, F., & Nguyên, P. (2015) · Seminars in Dialysis · doi:10.1111/sdi.12380 · Cited by 71
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“published data from a retrospective cohort analysis of 1,671 prevalent hemodialysis patients with atrial fibrillation”
Chan, K. E., Ikizler, T. A., Gamboa, J. L., Yu, C., Hakim, R. M., & Brown, N. J. (2011) · Kidney International · doi:10.1038/ki.2011.228 · Cited by 67
“[34–37] Chan et al.”
Providencia, R. A., Marijon, É., Bovéda, S., Barra, S., Narayanan, K., Heuzey, J. L., Gersh, B. J., & Gonçalves, L. M. M. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.05.048 · Cited by 67
Chokesuwattanaskul, R., Thongprayoon, C., Tanawuttiwat, T., Kaewput, W., Pachariyanon, P., & Cheungpasitporn, W. (2018) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.13331 · Cited by 69
Wakasugi, M., Kazama, J. J., Tokumoto, A., Suzuki, K., Kageyama, S., Ohya, K., Miura, Y., Kawachi, M., Takata, T., Nagai, M., et al. (2013) · Clinical and Experimental Nephrology · doi:10.1007/s10157-013-0885-6 · Cited by 66
“0 had a significantly higher risk of stroke [8].”
BackgroundResultWarfarin in haemodialysis patients with atrial fibrillation: what benefit?
Yang, F., Chou, D. E., Schweitzer, P., & Hanon, S. (2010) · EP Europace · doi:10.1093/europace/euq387 · Cited by 65
Atrial fibrillation and risk of stroke in dialysis patients
Wetmore, J. B., Ellerbeck, E. F., Mahnken, J. D., Phadnis, M. A., Rigler, S. K., Mukhopadhyay, P., Spertus, J. A., Zhou, X., Hou, Q., & Shireman, T. I. (2013) · Annals of Epidemiology · doi:10.1016/j.annepidem.2012.12.011 · Cited by 65
“Finally, to compare results of our dually-eligible population to that of other populations [4, 14], we tested whether the CHADS2 risk stratification scheme used in the general population to predict stroke risk in patients with AF [15] would perform well in broadly risk-stratifying duallyeligible chronic dialysis patie…”
BackgroundResultInfluentialStroke in Dialysis and Chronic Kidney Disease
Power, A. J. (2013) · Blood Purification · doi:10.1159/000356086 · Cited by 63
Kim, J. S., & Hwang, H. S. (2021) · Korean Circulation Journal · doi:10.4070/kcj.2021.0995 · Cited by 64
Stroke prevention strategies in high-risk patients with atrial fibrillation
Kotalczyk, A., Mazurek, M., Kalarus, Z. F., Potpara, T., & Lip, G. Y. H. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00459-3 · Cited by 60
Chronic Kidney Disease and Stroke
Husseini, N. E., Kaskar, O. B., & Goldstein, L. B. (2014) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2014.09.001 · Cited by 57
Systemic Anticoagulation Considerations in Chronic Kidney Disease
Dager, W. E., & Kiser, T. H. (2010) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2010.06.002 · Cited by 57
“Because of the complexity of managing warfarin, and increased risk of adverse outcomes in the CKD setting, warfarin management should be deferred when possible to dedicated anticoagulation services.(15)”
BackgroundWang, T. K. M., Sathananthan, J., Marshall, M. R., Kerr, A., & Hood, C. (2015) · Heart Lung and Circulation · doi:10.1016/j.hlc.2015.08.012 · Cited by 57
“Mixed results have been reported in other studies, that warfarin also has no effect [5,9,12,13,22] or even increases [10,11] the risk of ischaemic strokes in dialysis patients with AF.”
ResultInfluentialChan, P., Huang, D., Yip, P.-S., Hai, J. J., Tse, H., Chan, T. M., Lip, G. Y. H., Lo, W.-K., & Siu, C. (2015) · EP Europace · doi:10.1093/europace/euv289 · Cited by 55
“Likewise, in a cohort of 1671 haemodialysis patients with AF from North America, warfarin therapy was associated with nearly two-fold increase in stroke.(12) On the other hand, the risk of haemorrhagic stroke amongst haemodialysis patients with AF receiving also increases substantially.”
BackgroundSu, X., Yan, B., Wang, L., Lv, J., Cheng, H., & Chen, Y. (2021) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2021.02.328 · Cited by 54
A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease
Parker, K., Hartemink, J., Saha, A., Mitra, R., Lewis, P. J., Power, A. J., Choudhuri, S., Mitra, S., & Thachil, J. V. (2022) · Journal of Nephrology · doi:10.1007/s40620-022-01413-x · Cited by 61
“However, there were nine studies in dialysis patients that found no difference in major bleeding between those anticoagulated and not [5, 49, 51, 52, 55, 63, 64, 66, 68].”
BackgroundChen, H.-Y., Ou, S., Huang, C., Lee, P., Chou, K.-J., Lin, P., & Su, Y. (2021) · Clinical Drug Investigation · doi:10.1007/s40261-021-01016-7 · Cited by 56
Cardiovascular disease and chronic kidney disease
Gargiulo, R., Suhail, F., & Lerma, E. V. (2015) · Disease-a-Month · doi:10.1016/j.disamonth.2015.07.005 · Cited by 54
Role of direct oral anticoagulants in patients with kidney disease
Derebail, V. K., Rheault, M. N., & Kerlin, B. A. (2019) · Kidney International · doi:10.1016/j.kint.2019.11.027 · Cited by 56
Pokorney, S. D., Black‐Maier, E., Hellkamp, A. S., Friedman, D. J., Vemulapalli, S., Granger, C. B., Thomas, L. E., Peterson, E. D., & Piccini, J. P. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.01.019 · Cited by 54
Oral Anticoagulant Therapy in Atrial Fibrillation Patients at High Stroke and Bleeding Risk
Potpara, T., & Lip, G. Y. H. (2015) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2015.07.003 · Cited by 52
“of warfarin in those with AF [62, 75, 76], whilst warfarin (but not aspirin) treatment was associated with a significant reduction of stroke or systemic embolism (HR 0.”
BackgroundEvidence for the Prevention and Treatment of Stroke in Dialysis Patients
Herrington, W. G., Haynes, R., Staplin, N., Emberson, J., Baigent, C., & Landray, M. (2014) · Seminars in Dialysis · doi:10.1111/sdi.12281 · Cited by 51
“Five recent observational analyses of the association between warfarin prescription and stroke in those on dialysis with AF have yielded conflicting results (perhaps reflecting different amounts of residual confounding between these studies (75)): one study in US dialysis patients with AF found warfarin prescription t…”
ResultNochaiwong, S., Ruengorn, C., Awiphan, R., Dandecha, P., Noppakun, K., & Phrommintikul, A. (2016) · Open Heart · doi:10.1136/openhrt-2016-000441 · Cited by 52
Evidence-Based Cardiology in Hemodialysis Patients
Allon, M. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013060632 · Cited by 52
Cardiovascular Risk Assessment Before and After Kidney Transplantation
Glicklich, D., & Vohra, P. (2014) · Cardiology in Review · doi:10.1097/crd.0000000000000012 · Cited by 52
“bleeding and bleeding after invasive procedures such as angiography or biopsy.(71,72) Therefore, it is controversial whether patients with ESRD and Afib should receive chronic anticoagulant therapy with”
BackgroundAnticoagulation in chronic kidney disease: current status and future perspectives
Jones, A. P., Swan, D., Lisman, T., Barnes, G. D., & Thachil, J. V. (2023) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2023.09.020 · Cited by 51
Anticoagulants and acute kidney injury: clinical and pathology considerations
Brodsky, S. V. (2014) · Kidney Research and Clinical Practice · doi:10.1016/j.krcp.2014.11.001 · Cited by 48
“They reported that patients with severe CKD were at higher risk for both over-anticoagulation and major hemorrhage, as compared with patients with mild or moderate CKD. Chan et al [15] reported that warfarin therapy is associated with higher mortality among hemodialysis patients than in non–end-stage renal disease (ES…”
BackgroundOral anticoagulation in patients with chronic kidney disease
Malhotra, K., Ishfaq, M. F., Goyal, N., Katsanos, A. H., Parissis, J., Alexandrov, A. W., Alexandrov, A. V., & Tsivgoulis, G. K. (2019) · Neurology · doi:10.1212/wnl.0000000000007534 · Cited by 53
Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients
Krüger, T., Brandenburg, V. M., Schlieper, G., Marx, N., & Floege, J. (2012) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfs485 · Cited by 46
“• A retrospective analysis of 1671 incident HD patients with preexisting atrial fibrillation investigated the association of ASS or clopidogrel versus warfarin versus no therapy with stroke and death [31].”
BackgroundWarfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis
Yoon, C.-Y., Noh, J., Jhee, J. H., Chang, T. I., Kang, E. W., Kee, Y. K., Kim, H., Park, S., Yun, H., Jung, S.-Y., et al. (2017) · Stroke · doi:10.1161/strokeaha.117.017114 · Cited by 46
Chen, J., Lin, L., Yang, Y., Hwang, J., Chen, P., & Lin, J.-L. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.09.140 · Cited by 45
Morbidity and treatment in patients with atrial fibrillation and chronic kidney disease
Reinecke, H., Näbauer, M., Gerth, A., Limbourg, T., Treszl, A., Engelbertz, C. M., Eckardt, L., Kirchhof, P. F., Wegscheider, K., Ravens, U., et al. (2014) · Kidney International · doi:10.1038/ki.2014.195 · Cited by 47
Akimoto, T., Ito, C., Kato, M., Ogura, M., Muto, S., & Kusano, E. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.06.044 · Cited by 44
Coumarins and survival in incident dialysis patients
Knöll, F., Sturm, G., Lamina, C., Zitt, E., Lins, F., Freistätter, O., Kronenberg, F., Lhotta, K., & Neyer, U. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfr341 · Cited by 44
“Increased risk for haemorrhages [5] and the potential to accelerate vascular calcification as an effect of coumarins on vitamin K-dependent calcification inhibitor proteins [6] are put forward as main arguments against oral anticoagulation in dialysis patients.”
Background
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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