What are the risks of Hypertension (HIF) for patients on high dose Erythropoiesis-Stimulating Agents (ESA)?

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Last updated: March 11, 2025View editorial policy

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From the Guidelines

Patients on high-dose Erythropoiesis-Stimulating Agents (ESAs) are at increased risk of hypertension and thrombotic events, and therefore, careful monitoring of blood pressure and thrombotic risk factors is essential. The use of ESAs has been associated with an increased risk of thrombosis, including arterial and venous events, with a relative risk ranging from 48% to 69% compared to control patients 1. Additionally, patients with previous risk factors for thrombosis, such as hypertension, may be at higher risk for thrombosis with the use of ESAs 1.

Some key points to consider when managing patients on high-dose ESAs include:

  • Evaluating the risk factors for thrombosis, such as history of thromboembolism, heritable mutation, hypercoagulability, elevated prechemotherapy platelet counts, recent surgery, hormonal agents, and comorbidities such as hypertension 1
  • Monitoring hemoglobin levels regularly to avoid excessive increases in hemoglobin, which may increase the risk of thrombotic events 1
  • Adjusting ESA doses based on hemoglobin response and iron status to minimize the risk of thrombosis and other adverse events 1
  • Considering alternative treatments, such as hypoxia-inducible factor (HIF) stabilizers, for patients with chronic kidney disease who are on high-dose ESAs with inadequate response [@Example@]

It is essential to weigh the benefits and risks of ESA therapy in patients with cancer and chronic kidney disease, and to carefully monitor patients for signs and symptoms of thromboembolism and other adverse events 1. By taking a careful and individualized approach to ESA therapy, healthcare providers can help minimize the risks associated with these agents and optimize patient outcomes.

From the Research

Risks of Hypertension for Patients on High Dose Erythropoiesis-Stimulating Agents (ESA)

  • The use of high-dose ESA therapy has been associated with increased risks of adverse outcomes, including cardiovascular events and mortality 2, 3.
  • A metaregression analysis found that higher ESA doses were associated with increased all-cause mortality, cardiovascular events, and hypertension 2.
  • A retrospective study found that high-dose ESA therapy was associated with increased all-cause mortality and a negative correlation between ESA dose and hemoglobin levels 3.
  • The mechanism by which ESA dose affects mortality risk is unclear, but it may be related to the elevated ESA dosage required to target hemoglobin levels or underlying morbid conditions that lead to ESA resistance 3.

Cardiovascular Risks

  • Higher ESA doses have been associated with increased rates of hypertension, stroke, and thrombotic events, including dialysis vascular access-related thrombotic events 2.
  • However, an observational study found that ESA use was not associated with an excess of thrombotic events, including ischemic stroke, myocardial infarction, and venous thromboembolism 4.
  • The relationship between ESA dose and cardiovascular risk is complex and may depend on various factors, including patient characteristics, ESA molecule used, and target hemoglobin level 5.

ESA Dose and Mortality Risk

  • Higher ESA doses have been consistently associated with increased mortality risk, independent of hemoglobin level 2, 3.
  • The use of high-dose ESA therapy may be associated with a higher risk of cardiovascular complications, including hypertension, stroke, and thrombotic events 2.
  • Further research is needed to fully understand the relationship between ESA dose and mortality risk and to determine the optimal ESA dosing strategy for patients with chronic kidney disease 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2013

Research

Erythropoiesis-stimulating agents: dose and mortality risk.

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation, 2015

Research

Are all erythropoiesis-stimulating agents created equal?

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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