Intravenous iron supplementation practices and short-term risk of cardiovascular events in hemodialysis patients

• Published in: PloS one 2013-11, Vol.8 (11), p.e78930
• Main Authors: Kshirsagar, Abhijit V, Freburger, Janet K, Ellis, Alan R, Wang, Lily, Winkelmayer, Wolfgang C, Brookhart, M Alan
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Aged; Anemia; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - etiology; Cardiovascular Diseases - mortality; Cerebral infarction; Dialysis; Dosage; Dose-Response Relationship, Drug; Drug dosages; Epidemiology; Exposure; Female; Follow-Up Studies; Food and nutrition; Hazards; Health aspects; Health risks; Health services; Hemodialysis; Hemodialysis patients; Hospitalization - statistics & numerical data; Humans; Infarction; Intravenous administration; Iron; Iron - administration & dosage; Iron - adverse effects; Iron in the body; Kidney diseases; Laboratories; Maintenance; Male; Middle Aged; Morbidity; Mortality; Myocardial infarction; Outcome Assessment (Health Care) - statistics & numerical data; Patients; Physiological aspects; Proportional Hazards Models; Renal Dialysis - statistics & numerical data; Retrospective Studies; Risk Factors; Safety; Safety engineering; Short term; Stroke; Subgroups; Supplementation; Supplements; Survival Rate; Time Factors; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078930

Intravenous iron supplementation is widespread in the hemodialysis population, but there is uncertainty about the safest dosing strategy. We compared the safety of different intravenous iron dosing practices on the risk of adverse cardiovascular outcomes in a large population of hemodialysis patients. A retrospective cohort was created from the clinical database of a large dialysis provider (years 2004-2008) merged with administrative data from the United States Renal Data System. Dosing comparisons were (1) bolus (consecutive doses ≥ 100 mg exceeding 600 mg during one month) versus maintenance (all other iron doses during the month); and (2) high (> 200 mg over 1 month) versus low dose (≤ 200 mg over 1 month). We established a 6-month baseline period (to identify potential confounders and effect modifiers), a one-month iron exposure period, and a three-month follow-up period. Outcomes were myocardial infarction, stroke, and death from cardiovascular disease. 117,050 patients contributed 776,203 unique iron exposure/follow-up periods. After adjustment, we found no significant associations of bolus dose versus maintenance, hazards ratio for composite outcome, 1.03 (95% C.I. 0.99, 1.07), or high dose versus low dose intravenous iron, hazards ratio for composite outcome, 0.99 (95% C.I. 0.96, 1.03). There were no consistent associations of either high or bolus dose versus low or maintenance respectively among pre-specified subgroups. Strategies favoring large doses of intravenous iron were not associated with increased short-term cardiovascular morbidity and mortality. Investigation of the long-term safety of the various intravenous iron supplementation strategies may still be warranted.