Comparative Safety of Long-Acting vs. Short-Acting Erythropoiesis-Stimulating Agents Among Patients Undergoing Hemodialysis

Raj Desai; Ikenna Unigwe; Munaza Riaz; Steven M Smith; Ashutosh M Shukla; Rajesh Mohandas; Nakyung Jeon; Haesuk Park

doi:10.1002/cpt.3271

Comparative Safety of Long-Acting vs. Short-Acting Erythropoiesis-Stimulating Agents Among Patients Undergoing Hemodialysis

Clin Pharmacol Ther. 2024 Apr 17. doi: 10.1002/cpt.3271. Online ahead of print.

Authors

Raj Desai¹, Ikenna Unigwe¹, Munaza Riaz¹, Steven M Smith^{1

2

3}, Ashutosh M Shukla^{3

4}, Rajesh Mohandas⁵, Nakyung Jeon⁶, Haesuk Park^{1

2}

Affiliations

¹ Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
² Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA.
³ College of Medicine, University of Florida, Gainesville, Florida, USA.
⁴ North Florida South Georgia Veterans Healthcare System, Gainesville, Florida, USA.
⁵ Division of Nephrology and Hypertension, Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana, USA.
⁶ College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Korea.

PMID: 38629679
DOI: 10.1002/cpt.3271

Abstract

Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.