Abstract
BACKGROUND
Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality.
STUDY DESIGN
Systematic review of the literature and meta-analysis.
SETTING & POPULATION
Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis.
SELECTION CRITERIA FOR STUDIES
We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months' duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO.
INTERVENTION
DPO versus EPO.
OUTCOME
All-cause mortality.
RESULTS
We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic=4.60; P=0.8).
LIMITATIONS
Generalizability to nontrial populations is uncertain.
CONCLUSIONS
Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents.
TY - JOUR
T1 - Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis.
AU - Wilhelm-Leen,Emilee R,
AU - Winkelmayer,Wolfgang C,
Y1 - 2015/01/28/
PY - 2014/07/11/received
PY - 2014/12/21/accepted
PY - 2015/2/1/entrez
PY - 2015/2/1/pubmed
PY - 2015/9/12/medline
KW - Erythropoiesis-stimulating agents
KW - anemia
KW - carbohydrate side chain
KW - chronic kidney disease (CKD)
KW - darbepoetin alfa (DPO)
KW - drug safety
KW - end-stage renal disease (ESRD)
KW - epoetin alfa (EPO)
KW - hemoglobin variability
KW - meta-analysis
KW - mortality
KW - recombinant human erythropoietin (rHuEPO)
SP - 69
EP - 74
JF - American journal of kidney diseases : the official journal of the National Kidney Foundation
JO - Am J Kidney Dis
VL - 66
IS - 1
N2 - BACKGROUND: Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality. STUDY DESIGN: Systematic review of the literature and meta-analysis. SETTING & POPULATION: Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis. SELECTION CRITERIA FOR STUDIES: We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months' duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO. INTERVENTION: DPO versus EPO. OUTCOME: All-cause mortality. RESULTS: We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic=4.60; P=0.8). LIMITATIONS: Generalizability to nontrial populations is uncertain. CONCLUSIONS: Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents.
SN - 1523-6838
UR - https://www.unboundmedicine.com/medline/citation/25636816/Mortality_risk_of_darbepoetin_alfa_versus_epoetin_alfa_in_patients_with_CKD:_systematic_review_and_meta_analysis_
DB - PRIME
DP - Unbound Medicine
ER -
