Stroke is a major cause of death and disability in end stage renal disease (ESRD) population on dialysis. Chronic atrial fibrillation (AF), common in the dialysis population, is a potentially-modifiable stroke risk factor. Warfarin, a well-studied intervention used to reduce stroke risk in the general population with AF, is considered appropriate therapy for dialysis patients with AF by the National Kidney Foundation. However, use rates of warfarin appear to be low even in suitable dialysis patients, which probably originates from a deep sense of skepticism among nephrologists that the results of randomized controlled trials of warfarin in the non-dialysis population are applicable to generally frail dialysis patients. Many critical issues regarding both stroke and warfarin use in dialysis patients with AF require urgent examination. An understanding of how warfarin is used in the setting of stroke risk is imperative, since bedside practitioners, guideline-forming thought leaders, and healthcare policymakers are operating in an information vacuum. Patterns of warfarin use for stroke prevention in AF have never been reported in a large sample of U.S. dialysis patients, primarily because the tools required to link longitudinal medication prescriptions to medical claims-based diagnoses at the level of the individual patient have never before been widely available. This proposal seeks to determine how demographic factors, comorbidities, and healthcare system factors (such as degree of urbanicity and the profit status of dialysis units) are associated with warfarin prescription in the dialysis population. Additionally, whether foundational healthcare system factors are associated with variation in stroke rates in this population will be examined. These questions will be investigated through the use of observational data, which offers the opportunity to efficiently undertake a large study of determinants of warfarin use in dialysis patients with AF. To accomplish these aims, a novel linkage between the United States Renal Data System (USRDS) Medicare data and Medicaid medication claims data will be used. Ultimately, the K23 project proposed here is designed to develop the applicant into a successful independent health services researcher who can investigate issues of stroke and cardiovascular disease prevention in ESRD, ultimately contributing to the reduction of disease burden in this growing population.

Public Health Relevance

Reducing death from cardiovascular causes in dialysis patients is central to the mission of the NIH. Given both the size of the ESRD population as well as the prevalence of cardiovascular disease in these patients, investigation into the factors associated with warfarin use to reduce stroke risk is of the utmost importance. Little is presently known about this topic;the present application will be a critical first step in determining the factors associated with use of this important therapy. Stroke is very common in dialysis patients. A major cause of stroke is atrial fibrillation, for which the blood-thinning medicine warfarin can be prescribed to lower stroke risk but which is prescribed infrequently in dialysis patients for uncertain reasons. To help determine why warfarin is used infrequently, the proposed project will create a novel linked database using Medicare and state Medicaid databases to ascertain the demographic, comorbidity, and healthcare system factors (such as profit status and degree of urbanicity of dialysis units) determining warfarin use in the large and growing dialysis population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK085378-03
Application #
8246094
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2010-04-01
Project End
2013-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
3
Fiscal Year
2012
Total Cost
$175,876
Indirect Cost
$13,028
Name
University of Kansas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Wetmore, James B; Phadnis, Milind A; Mahnken, Jonathan D et al. (2014) Race, ethnicity, and state-by-state geographic variation in hemorrhagic stroke in dialysis patients. Clin J Am Soc Nephrol 9:756-63
Shireman, Theresa I; Phadnis, Milind A; Wetmore, James B et al. (2014) Antihypertensive medication exposure and cardiovascular outcomes in hemodialysis patients. Am J Nephrol 40:113-22
Phadnis, Milind A; Shireman, Theresa I; Wetmore, James B et al. (2014) Estimation of Drug Effectiveness by Modeling Three Time-dependent Covariates: An Application to Data on Cardioprotective Medications in the Chronic Dialysis Population. Stat Biopharm Res 6:229-240
Wetmore, James B; Mahnken, Jonathan D; Rigler, Sally K et al. (2013) Impact of race on cumulative exposure to antihypertensive medications in dialysis. Am J Hypertens 26:234-42
Wetmore, James B; Ellerbeck, Edward F; Mahnken, Jonathan D et al. (2013) Atrial fibrillation and risk of stroke in dialysis patients. Ann Epidemiol 23:112-8
Rigler, Sally K; Wetmore, James B; Mahnken, Jonathan D et al. (2013) Impact of a modified data capture period on Liu comorbidity index scores in Medicare enrollees initiating chronic dialysis. BMC Nephrol 14:51
Wetmore, James B; Mahnken, Jonathan D; Rigler, Sally K et al. (2012) The prevalence of and factors associated with chronic atrial fibrillation in Medicare/Medicaid-eligible dialysis patients. Kidney Int 81:469-76
Wetmore, James B; Mahnken, Jonathan D; Mukhopadhyay, Purna et al. (2011) Geographic variation in cardioprotective antihypertensive medication usage in dialysis patients. Am J Kidney Dis 58:73-83