Most dialysis patients in the US are >65 years and are at increased cardiovascular risk. The prevalence of atrial fibrillation (AF) is higher in dialysis patients, but estimates vary widely (7%-27%). Further, controversy persists in defining its optimal management in this setting. AF is an important risk factor for thromboembolic events such as stroke, for which dialysis patients are already at increased risk. In the general population, oral anticoagulation with warfarin reduces this risk substantially, and its benefits have been shown to clearly outweigh an increased bleeding risk. In dialysis patients, however, the relationship between these benefits and risks is less clear. While warfarin may reduce thromboembolic events, dialysis patients are at an increased bleeding risk even in the absence of warfarin. Thus, the risk of warfarin-related hemorrhage is likely to be much higher in dialysis patients. Little is known about actual warfarin treatment patterns of dialysis patients with AF, and no trials or formal benefit-risk assessments of warfarin in these patients have been conducted.
In Specific Aim 1, the prevalence of AF in a very large population of older dialysis patients with prescription drug coverage will be measured (N=12,812) and clinical and demographic characteristics associated with AF will be defined.
In Specific Aim 2, the rates of warfarin treatment of AF in this population will be assessed and factors associated with its use vs. non-use will be defined.
In Specific Aim 3, differences in outcomes between treated vs. untreated dialysis patients with AF will be assessed by measuring rates of thromboembolic and bleeding events in AF patients receiving warfarin, compared to similar untreated AF patients.
This Aim will also be studied in a separate cohort of dialysis patients from a large national dialysis provider. Control for confounding will be performed with multivariable regression as well as propensity score methods. This feasibility study (R21) will be used to develop relevant evidence that will help inform a common treatment dilemma in dialysis patient care. Subsequently, an R01 grant submission will be developed, proposing US-wide follow-up studies to clarify these issues even further.

Public Health Relevance

We will study a common disorder of irregular heartbeat in older patients with severe kidney failure. That condition increases the risk of stroke, which is preventable with an existing medication. Since it is not known whether this drug is also the best treatment for such patients on dialysis, our work will study this question and thus lead to better care of these patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DK077336-02
Application #
7896845
Study Section
Special Emphasis Panel (ZRG1-RUS-F (51))
Program Officer
Eggers, Paul Wayne
Project Start
2009-08-01
Project End
2011-12-31
Budget Start
2010-09-15
Budget End
2011-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$200,000
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Lenihan, Colin R; Montez-Rath, Maria E; Shen, Jenny I et al. (2015) Correlates and outcomes of warfarin initiation in kidney transplant recipients newly diagnosed with atrial fibrillation. Nephrol Dial Transplant 30:321-9
Shen, Jenny I; Montez-Rath, Maria E; Lenihan, Colin R et al. (2015) Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation. Am J Kidney Dis 66:677-88
Shilane, D; Hlatky, M A; Winkelmayer, W C et al. (2015) Coronary artery bypass graft type and outcomes in maintenance dialysis. J Cardiovasc Surg (Torino) 56:463-71
Shen, Jenny I; Mitani, Aya A; Winkelmayer, Wolfgang C (2014) Heparin use in hemodialysis patients following gastrointestinal bleeding. Am J Nephrol 40:300-7
Lenihan, Colin R; Montez-Rath, Maria E; Winkelmayer, Wolfgang C et al. (2013) Multivessel coronary revascularization and outcomes in kidney transplant recipients. Transpl Int 26:1080-7
Shen, Jenny I; Mitani, Aya A; Chang, Tara I et al. (2013) Use and safety of heparin-free maintenance hemodialysis in the USA. Nephrol Dial Transplant 28:1589-602
Lenihan, C R; Montez-Rath, M E; Scandling, J D et al. (2013) Outcomes after kidney transplantation of patients previously diagnosed with atrial fibrillation. Am J Transplant 13:1566-75
Winkelmayer, Wolfgang C; Liu, Jun; Patrick, Amanda R et al. (2012) Prevalence of atrial fibrillation and warfarin use in older patients receiving hemodialysis. J Nephrol 25:341-53
Goldstein, Benjamin A; Arce, Cristina M; Hlatky, Mark A et al. (2012) Trends in the incidence of atrial fibrillation in older patients initiating dialysis in the United States. Circulation 126:2293-301
Shen, Jenny I; Turakhia, Mintu P; Winkelmayer, Wolfgang C (2012) Anticoagulation for atrial fibrillation in patients on dialysis: are the benefits worth the risks? Curr Opin Nephrol Hypertens 21:600-6

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