Wilhelm-Leen Emilee R, Winkelmayer Wolfgang C
Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA.
Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA; Section of Nephrology, Baylor College of Medicine, Houston, TX.
Am J Kidney Dis. 2015 Jul;66(1):69-74. doi: 10.1053/j.ajkd.2014.12.012. Epub 2015 Jan 28.
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.
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.
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.
DPO versus EPO.
All-cause mortality.
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).
Generalizability to nontrial populations is uncertain.
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.
促红细胞生成素α（EPO）和达比加群酯（DPO）是促红细胞生成剂，广泛且可互换地用于治疗晚期慢性肾病和终末期肾病患者的贫血。尚无研究专门比较EPO和DPO之间包括死亡率在内的硬研究结局风险。
文献系统评价和荟萃分析。
纳入比较EPO与DPO治疗慢性肾病成人贫血（包括需要透析者）的随机试验的患者。
我们使用预定义的检索词和数据提取工具，对文献（PubMed、CENTRAL、SCOPUS和EMBASE，所有年份）和行业资源进行了系统检索。然后总结了这些试验的关键特征和结果，并对持续时间至少3个月的试验进行随机效应荟萃分析，以确定随机分配至DPO与EPO的患者之间死亡率的汇总OR。
DPO与EPO。
全因死亡率。
我们确定了9项符合既定纳入标准的试验。总体而言，荟萃分析纳入了2024例患者，其中126例在随访期间死亡，随访时间为20至52周。我们发现随机分配至DPO与EPO的患者之间死亡率无显著差异（OR，1.33；95%CI，0.88 - 2.01）。未检测到各研究间的治疗异质性（Q统计量 = 4.60；P = 0.8）。
对非试验人群的可推广性尚不确定。
直接比较DPO和EPO的试验较少，且随访有限。总体而言，未发现特定促红细胞生成剂对死亡率有影响，但置信区间较宽，且仍与DPO造成的相当大危害相符。在缺乏足够样本量的随机试验的情况下，需要进行观察性上市后比较有效性研究，以更好地描述这些促红细胞生成剂的长期安全性概况。
