Winkelmayer Wolfgang C, Goldstein Benjamin A, Mitani Aya A, Ding Victoria Y, Airy Medha, Mandayam Sreedhar, Chang Tara I, Brookhart M Alan, Fishbane Steven
Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX.
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
Am J Kidney Dis. 2017 Jun;69(6):771-779. doi: 10.1053/j.ajkd.2016.10.031. Epub 2017 Jan 4.
Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex.
Retrospective cohort study of incident HD patients.
SETTING & PARTICIPANTS: Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure.
Facility-level use of iron sucrose versus ferric gluconate.
Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths.
HRs.
We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96).
Unobserved selection bias from nonrandom treatment assignment.
Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.
对于血液透析（HD）患者常规使用的不同静脉铁剂配方在长期安全性方面是否存在差异存在争议。我们利用一项自然实验来比较在主要（≥90%的患者）使用蔗糖铁与葡萄糖酸铁钠复合物的设施中开始HD治疗的患者的结局。
对新发病HD患者的回顾性队列研究。
利用美国肾脏数据系统，我们在地理区域和中心特征方面对主要使用葡萄糖酸铁的HD设施与使用蔗糖铁的类似设施进行了严格匹配。随后，将新发病HD患者分配到其所在设施的铁剂配方暴露组。
设施层面使用蔗糖铁与葡萄糖酸铁。
对患者进行随访，观察任何原因、心血管原因或感染原因导致的死亡情况。对参加医疗保险的患者进行随访，观察感染性和心血管（中风或心肌梗死）住院情况以及相应原因特异性死亡的综合结局。
风险比（HRs）。
我们将2015个蔗糖铁设施与2015个葡萄糖酸铁设施进行了匹配，其中51603名患者（蔗糖铁组24911名；葡萄糖酸铁组26692名）随后开始了HD治疗。所有记录的患者特征在两组之间保持平衡。在超过49989人年的时间里，发生了10381例死亡（心血管原因3908例，感染原因1209例）。调整后的全因死亡率（HR，0.98；95%置信区间，0.93 - 1.03）、心血管死亡率（HR，0.96；95%置信区间，0.89 - 1.03）和感染性死亡率（HR，0.98；95%置信区间，0.86 - 1.13）在蔗糖铁设施和葡萄糖酸铁设施之间没有差异。在医疗保险受益人中，葡萄糖酸铁设施和蔗糖铁设施在致命或非致命心血管事件方面没有差异（HR，1.01；95%置信区间，0.93 - 1.09）。与葡萄糖酸铁设施相比，蔗糖铁设施中复合感染终点事件的发生频率较低（HR，0.92；95%置信区间，0.88 - 0.96）。
非随机治疗分配导致的未观察到的选择偏倚。
在几乎完全使用蔗糖铁与葡萄糖酸铁的设施中开始HD治疗的患者具有相似的长期结局。然而，在主要使用蔗糖铁的设施中进行透析的患者，其感染性住院和死亡情况略有下降。这种差异可能是由于残余混杂、随机因素或因果效应。
