The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis: A Competing Risk Analysis

Abstract

Background: Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear. Objective: The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses. Design: A national record linkage cohort study. Setting: All renal and stroke units in Scotland, UK. Patients: All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015). Measurements: Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records. Methods: Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke. Results: Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death. Limitations: Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available. Conclusions: The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.

Apixaban versus No Anticoagulation in Patients Undergoing Long-Term Dialysis with Incident Atrial Fibrillation

“…Nevertheless, inclusion of patients with new-onset atrial fibrillation, similar results in the intention-to-treat and as-treated analyses, and exclusion of patients who died within a short interval postdiagnosis, suggesting atrial fibrillation in the setting of a serious intercurrent illness, are important strengths of our analysis. In addition, use of competing risk models has been recently shown to be critically important in the analysis of atrial fibrillation data and is another strength of this study (21).…”

Stroke in Hemodialysis Patients Randomized to Different Intravenous Iron Strategies: A Prespecified Analysis from the PIVOTAL Trial

“…Some observational registry data supports the observation that lower hemoglobin is associated with increased risk of stroke in hemodialysis, but this has not been a consistent observation. 1,22,23 Other RCTs have reported the effect of anemia treatment regimens using ESAs in patients with CKD and/or requiring dialysis. In a RCT in incident hemodialysis patients, like those studied in PIVOTAL, 'full' correction of anemia with epoetin alfa to a hemoglobin target of 135-145 g/L compared to a target of 95-115 g/L was associated with a significantly higher incidence of stroke (4% vs 1%, p=0.045) over 94 weeks follow-up 24 .…”

Effects of Mesenchymal Stem Cells Therapy on Cardiovascular Risk Factors in Experimental Diabetic Kidney Disease

“…However, they are still prone to cardiovascular complications and it remains a major cause of morbidity and mortality. 34 Cardiovascular events, particularly heart failure and atherosclerotic events, have a major impact on health-related quality of life in ESRD. Health care systems actively endeavor continuous efforts to predict these events in an attempt to improve quality of life of patients with ESRD.…”