title: Safety of Intravenous Iron in Hemodialysis: Longer-term Comparisons of Iron Sucrose Versus Sodium Ferric Gluconate Complex.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Retrospective cohort study of incident HD patients.
  
  
  METHODS
  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.
  
  
  METHODS
  Facility-level use of iron sucrose versus ferric gluconate.
  
  
  RESULTS
  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.
  
  
  METHODS
  HRs.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Unobserved selection bias from nonrandom treatment assignment.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX. Electronic address: winkelma@bcm.edu.
authors.forename: Wolfgang C
authors.initials: WC
authors.lastname: Winkelmayer
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Goldstein
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA.
authors.forename: Aya A
authors.initials: AA
authors.lastname: Mitani
authors.affiliation: Center for Biomedical Informatics Research, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Victoria Y
authors.initials: VY
authors.lastname: Ding
authors.affiliation: Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: Medha
authors.initials: M
authors.lastname: Airy
authors.affiliation: Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Mandayam
authors.affiliation: Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Tara I
authors.initials: TI
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
authors.forename: M Alan
authors.initials: MA
authors.lastname: Brookhart
authors.affiliation: Division of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Great Neck, NY.
authors.forename: Steven
authors.initials: S
authors.lastname: Fishbane
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000740:Anemia / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007239:Infections / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D012189:Retrospective Studies
chemical_list: D005290:Ferric Compounds; D006397:Hematinics; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; C035552:ferric gluconate
keywords: Intravenous iron; cardiovascular; dialysis facility formulary; end-stage renal disease (ESRD); hemodialysis; infectious hospitalization; iron sucrose; mortality; myocardial infarction; natural experiment; safety; sodium ferric gluconate complex; stroke