Elsevier

Annals of Epidemiology

Volume 23, Issue 3, March 2013, Pages 112-118
Annals of Epidemiology

Atrial fibrillation and risk of stroke in dialysis patients

https://doi.org/10.1016/j.annepidem.2012.12.011Get rights and content

Abstract

Purpose

Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF.

Methods

A cohort of dually eligible (Medicare and Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke.

Results

Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (hazard ratio [HR], 1.26; 99% confidence interval [CI], 1.06–1.49; P = .0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African Americans (HR, 1.46; 99% CI, 1.08–1.96), Hispanics (HR, 1.64; 99% CI, 1.16–2.31), and others (HR, 1.76; 99% CI, 1.16–2.78) had higher rates than did Caucasians (all P < .001).

Conclusions

Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes owing to hemorrhage is much higher than in the general population.

Introduction

Stroke is a catastrophic health event and a leading cause of disability. In the general population, atrial fibrillation (AF) is a well-established risk factor for stroke [1]. We have recently reported that 7% of prevalent dialysis patients have chronic AF [2] (a rate 10-fold greater than that of the general population [3]), a finding that might suggest that chronic AF could be a major contributor to the stroke burden suffered by dialysis patients. Conversely, dialysis patients have a high burden of vascular disease, diabetes, and hypertension, all of which could conceivably modify the contribution of AF to stroke. As such, the contribution of AF to stroke in chronic dialysis patients is uncertain. Understanding the relationship between chronic AF and stroke in this unique population is particularly important given recent evidence suggesting that the risks of warfarin for stroke prophylaxis in AF may outweigh its benefits in dialysis patients [4], [5].

An additional issue of uncertainty is the rate of various stroke types in chronic dialysis patients. Reported stroke rates range from 15 [6], [7], [8], [9] up to nearly 50 [4], [10] events per 1000 patient-years (py). Similarly, the reported rates of stroke subtypes differ substantially. Although in the general population the ratio of ischemic to hemorrhagic strokes is about 6 or 7:1 [11], [12], in dialysis patients this ratio reportedly varies from one comparable with that of the general population (∼6:1 [5], [10], [11]) to one in which hemorrhagic strokes are distinctly common (∼3:1) [4], [9]. These findings suggest that improved characterization of stroke rates and types is needed for the dialysis population, in particular a determination of the differential rates of strokes during periods of chronic AF versus during “AF-free” time.

In the present study, we used a large cohort of incident, dually eligible (Medicare–Medicaid) chronic dialysis patients to investigate two important stroke-related questions. First, utilizing new information on the sensitivity and specificity of stroke-related International Classification of Disease (ICD-9) claims in identifying strokes from Medicare data [13], we determined ischemic and hemorrhagic stroke rates in chronic dialysis patients and divided these into at-risk (chronic AF-time) and non–at-risk (AF-free) times. Second, we determined the association of chronic AF and a broad spectrum of other covariates on ischemic, hemorrhagic, and all (combined) strokes using a recently reported chronic AF identification strategy [2] as well as a rigorous, time-varying approach to model AF. Finally, to compare results of our dually eligible population with 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 dually eligible chronic dialysis patients. A more complete understanding of these issues is critically important for evaluating the risks and benefits of potential therapies, such as long-term anticoagulation, for dialysis patients who have chronic AF.

Section snippets

Study design and data sources for analysis

We performed a retrospective cohort analysis of incident, dually eligible (Medicare–Medicaid) chronic dialysis patients. We examined dually eligible dialysis patients for two reasons. First, we have a long-standing interest in this population, which represents a particularly vulnerable group of medically needy individuals who are more likely to be indigent, female, and minority than general dialysis population [16]. Second, the definition of chronic AF relied, in part, on drug prescribing

Results

Figure 1 shows the construction of the study cohort. There were a total of 62,812 dually eligible individuals who initiated dialysis between January 1, 2000, and October 2, 2005 (i.e., who survived ≥90 days before our final date of December 31, 2005). We then eliminated individuals who had valvular heart disease or hyperthyroidism as well as the small number who had incomplete information, leaving 56,734 individuals in the final study sample.

The characteristics of the cohort are shown in Table 1

Discussion

In this study, we used a large cohort of incident, dually eligible chronic dialysis patients to determine the rate of new ischemic and hemorrhagic strokes and the risk of stroke conferred by chronic AF. To ensure rigor in our analysis, we treated chronic AF as a time-dependent covariate and also classified strokes using both sensitive and specific approaches. We found that there were 22.8 ischemic, 5.0 hemorrhagic, and 27.3 total strokes per 1000 py. We also found that, after adjustment for a

Acknowledgments

The authors thank Connie Wang, MD, and Amanda Gellhaus for technical assistance with manuscript preparation.

Funding for this study was provided by NIH (NIDDK) grants K23 DK085378-01 (J.B.W.) and R01 DK080111-02 (T.I.S.), by a National Kidney Foundation Young Investigator Award (J.B.W.), and by a Sandra A. Daugherty Foundation Grant (J.B.W.).

The data reported herein have been supplied by the United States Renal Data System (DUA#2007-10 & 2009-19) and the Centers for Medicare & Medicaid Services

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