Cardiovascular Toxicity of Epoetin-Alfa in Patients with Chronic Kidney Disease
Cardiovascular Toxicity of Epoetin-Alfa in Patients with Chronic Kidney Disease
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DOI：
10.1159/000351175
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发表时间：
2013-01-01
影响因子：
4.2
通讯作者：
Califf, Robert M.
中科院分区：
文献类型：
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作者：
McCullough, Peter A.;Barnhart, Huiman X.;Califf, Robert M.
背景资料：重组促红细胞生成素已成为慢性肾病患者护理的常规组成部分，减少了输血的需要，但增加了心血管事件的风险。我们对入组纠正血红蛋白和肾功能不全结局（CHOIR）试验的受试者进行了二次分析，以检查使用的促红细胞生成素-α维持剂量与达到的血红蛋白（Hb）之间的相互关系，无论治疗目标和随机分配如何。方法：我们对CHOIR试验进行了事后分析。入选标准为Hb < 11.0 g/dl，估计肾小球滤过率为15-50 ml/min/1.73 m2。要纳入本分析，受试者需要在4个月时无复合事件，接受促红细胞生成素-α治疗，并有≥ 1次基线后Hb测量。至首次事件或谴责时接受的平均每周剂量的促红细胞生成素-α是主要暴露变量，而第4个月时达到的Hb是代表受试者对治疗的潜在反应的混杂因素。主要结局是死亡、心力衰竭住院、卒中或心肌梗死的复合终点。在至事件发生时间分析中使用考克斯比例风险回归模型。结果如下：在1，244名拥有完整数据的受试者中，首次发生事件或谴责时，埃泊汀-阿尔法的平均每周剂量范围为143.3倍，从133单位/周到19，106单位/周。考克斯比例风险分析发现，无论治疗前4个月内Hb达到多少，Hb达到中间三分位数的患者（>11.5至10，095单位/周）与心血管事件风险增加相关。这些数据表明，每周一次的促红细胞生成素-α剂量，而不是达到的Hb，是观察到的主要结局的主要决定因素，表明这种红细胞刺激剂具有心血管毒性。版权所有（c）2013 S. Karger AG，巴塞尔
Background: Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events. We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin (Hb) irrespective of treatment target and randomized allocation. Methods: We performed a post hoc analysis from the CHOIR trial. Inclusion criteria were Hb < 11.0 g/dl and estimated glomerular filtration rates of 15-50 ml/min/1.73 m(2). To be included in the present analysis, subjects needed to be free of the composite event at 4 months, receive epoetin-alfa, and have >= 1 postbaseline Hb measurement. The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable, while the achieved Hb at month 4 was the confounder representing the subject's underlying response to treatment. The primary outcome was the composite of death, heart failure hospitalization, stroke, or myocardial infarction. A Cox proportional hazard regression model was used in time-to-event analysis. Results: Among 1,244 subjects with complete data, the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure. Cox proportional hazard analysis found that those in the middle tertile of Hb achieved (>11.5 to 10,095 units/week were associated with increased risks for cardiovascular events irrespective of the Hb achieved within the first 4 months of treatment. These data suggest the weekly epoetin-alfa dose and not the Hb achieved was a principal determinant in the primary outcome observed implicating a cardiovascular toxicity of this erythrocyte-stimulating agent. Copyright (c) 2013 S. Karger AG, Basel