From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (K.S.); and Department of Medicine, Cleveland Clinic, OH (J.B.Y.).
Circ Heart Fail. 2018 Feb;11(2):e004431. doi: 10.1161/CIRCHEARTFAILURE.117.004431.
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.
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.
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.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215.
促红细胞生成素刺激剂（如达贝泊汀α）反应不佳与糖尿病、慢性肾脏病和贫血患者的不良结局相关；但在心力衰竭中是否也是如此尚不清楚。
我们对 RED-HF 试验（心力衰竭中达贝泊汀α降低事件）进行了事后分析，该试验纳入了 1008 例射血分数降低的心力衰竭伴贫血（血红蛋白水平 9.0-12.0 g/dL）患者，随机分为达贝泊汀α组。我们检查了达贝泊汀α的造血反应与 28 个月随访期间全因死亡或首次心力衰竭住院的发生率之间的关系。就本研究而言，4 周后血红蛋白变化最低四分位数的患者被认为是无反应者。无反应者（n=252）的初始血红蛋白中位数变化为-0.25 g/dL，其余患者（n=756）的变化为+1.00 g/dL。肾功能更差、血钠水平更低、血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂的使用率更低与无反应相关。尽管低内源性促红细胞生成素水平有助于区分反应者和无反应者，但在多变量模型中其预测价值较差（C 统计量=0.69）。无反应者的全因死亡或首次心力衰竭住院发生率较高（风险比，1.25；95%置信区间，1.02-1.54），全因死亡率风险也较高（风险比，1.30；95%置信区间，1.04-1.63）。
达贝泊汀α反应不佳与贫血心力衰竭患者的不良结局相关。使用临床和生化生物标志物难以识别反应不佳的患者。
