Background: A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear.

Methods and Results: We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0–12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was −0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02–1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04–1.63) than responders.

Conclusions: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215.

背景：对糖尿病，慢性肾脏病和贫血等患者的促红细胞生成素刺激剂（如达比泊汀α）反应不良与不良后果有关。目前尚不清楚在心力衰竭中是否也如此。

方法和结果：我们对RED-HF试验进行了事后分析（Darbepoetin Alfa减少了心力衰竭的事件），其中将1008例收缩期心力衰竭和贫血（血红蛋白水平为9.0-12.0 g / dL）的患者随机分为darbepoetin alfa 。我们检查了28个月的随访中对达比泊汀α造血反应与全因死亡或首次心力衰竭住院的发生率之间的关系。为了本研究的目的，在4周后血红蛋白变化最低的四分位数中的患者被视为无反应。无反应者（n = 252）的中值初始血红蛋白变化为-0.25 g / dL，其余患者（n = 756）为+1.00 g / dL。肾功能恶化，钠水平降低，血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂的较少使用与无反应独立相关。尽管低内源性促红细胞生成素水平有助于区分反应者和非反应者，但其在多变量模型中的预测价值不佳（C统计量= 0.69）。无应答者的全因死亡或首次心力衰竭住院率更高（危险比为1.25； 95％的置信区间为1.02-1.54），全因死亡率的风险更高（危险比为1.30； 95％的置信区间为： 1.04–1.63）。

结论：贫血的心力衰竭患者对达比泊汀α的不良反应与预后较差有关。反应较差的患者很难使用临床和生化生物标记物进行鉴定。

临床试验注册： URL：https://www.clinicaltrials.gov。唯一标识符：NCT00358215。