Erythropoietin treatment does not increase stroke risk in patients receiving maintenance hemodialysis, according to “real-world” data from Taiwan.

Investigators matched 6474 patients treated with epoetin, darbepoetin alfa, or methoxy polyethylene glycol‐epoetin beta to 6474 patients not treated with erythropoietin-stimulating agents (ESAs) by age and sex from the general Taiwanese population, who have universal health insurance through the National Health Insurance (NHI) Bureau.

In adjusted Cox proportional hazards regression models, the risks for stroke overall and its subtypes ischemic, hemorrhagic, and unspecified stroke did not differ significantly between ESA users and nonusers, Kuen-Jer Tsai, PhD, of National Cheng Kung University and colleagues reported in the Journal of the American Heart Association.

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The groups had comparable distributions of comorbidities that can increase stroke risk, including anemia, hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, heart failure, and atrial fibrillation. The study lacked data on smoking, body mass index, physical activity, other lifestyle risk factors, and family history of stroke.

Dr Tsai’s team also analyzed stroke risk by tertiles of cumulative ESA dose. The risks for stroke were not significantly greater for patients in the high tertile who received 201 or more daily ESA doses in a year than for patients who received fewer total doses. The low tertile group with less than 71 daily ESA doses in a year had a significant 29% increased risk for ischemic stroke, but it was “clearly not dose-dependent,” according to the investigators. 

“According to the strategy of the NHI Bureau of Taiwan, the hemoglobin or hematocrit values in patients on dialysis who were prescribed low‐dose erythropoietin were relatively high…” the authors wrote. “Therefore, in patients in whom low‐dose erythropoietin was used, the hemoglobin values were more likely to exceed 12 g/dL, which could have resulted in higher risk of ischemic stroke in our study.”

The study lacked data on achieved hemoglobin levels, which is relevant because higher hemoglobin levels have been associated with greater cardiovascular risk. In Taiwan, NHI reimbursement criteria specify a hemoglobin target of 10 to 11 g/dL during erythropoietin therapy.

“Our recommendation is to target hemoglobin concentration in accordance with the strategy of the NHI Bureau of Taiwan, which is different from the targets in other parts of the world, in order to provide the benefits of therapy while diminishing its potential risks,” Dr Tsai and colleagues concluded.


Hung PH, Yeh CC, Hsiao CY, Muo CH, Hung KY, Tsai KJ. Erythropoietin use and the risk of stroke in patients on hemodialysis: a retrospective cohort study in Taiwan. J Am Heart Assoc. 2021 Jul 20;10(14). doi:10.1161/JAHA.120.019529