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The impact of continuous erythropoietin receptor activators in patients after heart transplantation with multifactorial anemia with chronic kidney disease

Susanne Mueller1, Ibrahim Gueler1, Matthias Helmschrott1, Christian A. Gleissner1, Mohammadreza Akhavanpoor1, Lutz Frankenstein1, Bastian Schmack2, Arjang Ruhparwar2, Philipp Ehlermann1, Christian Erbel1, Tom Bruckner3, Hugo A. Katus1, Andreas O. Doesch1
1 Department of Cardiology, University of Heidelberg, Heidelberg, Germany
2 Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
3 Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
[Applied Cardiopulmonary Pathophysiology 18: 3-11, 2014]


Background: Multifactorial anemia with chronic kidney disease (CKD) is a common problem after heart transplantation (HTX). Erythropoiesis-stimulating agents (ESAs) are commonly used to improve hemoglobin levels in patients with anemia due to CKD. With CERA (Continuous Erythropoietin Receptor Activator) a new therapeutic agent with a longer serum half time is available. However, data in patients after HTX are extremely limited. This study retrospectively evaluated the effects of anemia treatment with CERA versus conventional ESAs (Erythropoietin beta) in patients after HTX with anemia due to CKD. Additional emphasis was put on patients’ preference and adherence.
Patients and methods: A total of 20 ESA naive heart transplant recipients with anemia due to CKD were included and analyzed retrospectively. All patients had baseline hemoglobin levels below 11.0 g/dl. 10 patients (mean age 53.4 ± 10.2 years, mean time post HTX 0.7 ± 0.7 years, 9 male/1 female) were included in the CERA group and 10 patients (mean age 60.2 ± 12.9 years, mean time post HTX 5.5 ± 5.2 years, 7 male/3 female) in the conventional ESA group (Erythropoietin beta). Primary endpoint was the change in hemoglobin level from baseline to month four, eight and twelve months post initiation of either CERA or conventional ESAs. Hemoglobin target level was 12.0 g/dl. In addition, patients were asked to complete a patient self-assessment questionnaire regarding conventional ESA/CERA use.
Results: After 12 months of CERA and conventional ESA therapy, a statistically significant increase in mean hemoglobin levels was observed (CERA group: 9.0 ± 1.0 g/dl (baseline) vs. 11.8 ± 1.9 g/dl (month 12), P=0.005 vs. baseline, conventional ESA group 9.2 ± 1.1 g/dl (baseline) vs. 11.0 ± 2.2 g/dl (month 12), P=0.02 vs. baseline). In CERA patients, a continuous increase in mean hemoglobin levels was observed throughout the study period, whereas mean hemoglobin level was more fluctuant in conventional ESA patients. CERA and conventional ESA therapy were both well tolerated and no adverse events occurred during the study period. General pain level was significantly lower in the CERA group (CERA 1.9 ± 0.9 vs. conventional ESA 3.1 ± 1.0, P=0.03). In the CERA group, 2 patients answered to have skipped a single CERA dose (P=0.006 vs. conventional ESA group), no patient had skipped multiple doses (P=0.003 vs. conventional ESA group). In the conventional ESA group, 9 patients had skipped a single ESA dose and 7 patients had left out multiple doses. All patients preferred a longer dosing interval (P<0.0001).
Conclusions: CERA therapy demonstrated a continuous increase in hemoglobin level during the study period. Longer dosing intervals were advantageous as ease of dosing was more pronounced in CERA patients and the rate of missed doses was lower in CERA patients indicating a better adherence. Our results underline the importance of optimized patient adherence by longer dosing intervals in this selected patient population with a multitude of co-medications.

Keywords: continuous erythropoietin receptor activator, anemia, heart transplantation, hemoglobin, quality of life

Correspondence address:
Andreas O. Doesch, MD
Medizinische Klinik III
Kardiologie, Angiologie, Pulmologie
Im Neuenheimer Feld 410
69120 Heidelberg, Germany
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