Optimal Oral Iron Therapy for Iron Deficiency Anemia Among US Veterans.

Importance: Optimal oral iron supplementation strategy is unclear in patients with iron deficiency anemia (IDA) who have either normal kidney function (NKF) or chronic kidney disease (CKD). Objective: To investigate the association of different oral iron supplementation strategies with the change in hemoglobin and iron indices among patients with IDA with either NKF or CKD. Design, Setting, and Participants: This retrospective cohort study was conducted between 2009 and 2019 at nationwide Veterans Health Administration facilities. Eligible participants included veterans with IDA (defined as hemoglobin <12 g/dL and either iron saturation <20% or ferritin <50 ng/mL) who received their first outpatient prescription of oral iron. Patients were further divided into those with NKF (estimated glomerular filtration rate >60 mL/min/1.73 m2) and CKD (estimated glomerular filtration rate ≥15 mL/min/1.73 m2 and <60 mL/min/1.73 m2). Data analysis was conducted from February to October 2023. Exposures: Patients were classified into 3 groups based on their oral iron dosing schedule: daily (once a day), multiple doses per day (MDD; ≥2 times per day), or alternate-day dose (ADD). Main Outcomes and Measures: The primary outcomes were change of hemoglobin, ferritin, total iron binding capacity (TIBC), and iron saturation (ISAT), which were calculated with linear mixed-effects models. Results: A total of 71 677 veterans with IDA (63 202 male [88.2%] and 8475 female [11.8%]; mean [SD] age, 68.47 [13.09] years), including 47 201 with NKF and 24 476 with CKD, were identifed. In patients with NKF in the daily group, hemoglobin increased from baseline (estimated per-30-day difference [SE], 0.27 [0.00] g/dL; P < .001). In comparison with the daily group, hemoglobin increased more in the MDD group (estimated per-30-day difference [SE], 0.08 [0.03] g/dL; P < .001), but no difference was noted in the ADD group (estimated per-30-day difference [SE], -0.01 [0.01] g/dL; P = .38). Ferritin, ISAT, and TIBC results were similar, except TIBC showed less change in the ADD group compared with the daily group. Patients with CKD showed similar trends but smaller magnitudes in changes. Among patients with NKF, the adjusted mean increase in hemoglobin was 1.03 g/dL (95% CI, 1.01-1.06 g/dL) for those in the daily group, 1.38 g/dL (95% CI, 1.36-1.40 g/dL) for those in the MDD group, and 0.93 g/dL (95% CI, 0.84-1.02 g/dL) for those in the ADD group at 90 days. Among patients with CKD, the adjusted mean increase in hemoglobin was 0.71 g/dL (95% CI, 0.68-0.73 g/dL) for those in the daily group, 0.99 g/dL (95% CI, 0.97-1.01 g/dL) for those in the MDD group, and 0.62 g/dL (95% CI, 0.52-0.73 g/dL) for those in the ADD group at 90 days. Conclusions and Relevance: In this retrospective cohort study of veterans with IDA, there was no significant difference in the improvement of hemoglobin and iron indices between daily and ADD groups, but quickest improvement was observed in the MDD group. These findings suggest that the choice of oral iron therapy should depend on the rapidity of response desired and patient preference due to adverse effects.