Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 152; no. 4; pp. 821 - 829.e1
• Main Authors: Lam, Jameson R, Schneider, Jennifer L, Quesenberry, Charles P, Corley, Douglas A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2017
• Subjects: Acid Suppressing; Adult; Aged; Aged, 80 and over; Case-Control Studies; Epidemiology; Female; Gastroenterology and Hepatology; Histamine H2 Antagonists - administration & dosage; Histamine H2 Antagonists - adverse effects; Humans; Iron - deficiency; Malabsorption Syndromes - chemically induced; Male; Medications; Middle Aged; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - adverse effects; Time Factors; BE; OR; NSAID; International Classification of Disease, 9 th revision; PPI; odds ratio; Epidemiology; proton pump inhibitor; Kaiser Permanente Northern California; Barrett’s esophagus; GERD; ICD-9; histamine-2 receptor agonist; H2RA; Acid Suppressing; Medications; KPNC; gastroesophageal reflux disease; Iron Deficiency; nonsteroidal anti-inflammatory drug
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2016.11.023

Background & Aims Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) suppress gastric acid production, which can inhibit iron absorption. However, few data exist regarding whether these medications increase the risk of clinical iron deficiency. Methods A community-based case-control study evaluated the association between acid-suppressing medication use and the subsequent risk of iron deficiency. It contrasted 77,046 patients with new iron deficiency diagnoses (January 1999−December 2013), with 389,314 controls. Medication exposures, outcomes, and potential confounders used electronic databases. We excluded patients with pre-existing risk factors for iron deficiency. Associations were estimated using conditional logistic regression. Results Among cases, 2343 (3.0%) received a prior ≥2-year supply of PPIs and 1063 (1.4%) received H2RAs (without PPI use). Among controls, 3354 (0.9%) received a prior ≥2-year supply of PPIs and 2247 (0.6%) H2RAs. Both ≥2 years of PPIs (adjusted odds ratio, 2.49; 95% confidence interval, 2.35−2.64) and ≥2 years of H2RAs (odds ratio, 1.58; 95% CI, 1.46−1.71) were associated with an increased subsequent risk for iron deficiency. Among PPI users, the associations were stronger for higher daily doses (>1.5 vs <0.75 PPI pills/d; P  value interaction = .004) and decreased after medication discontinuation ( P -trend < .001). Some of the strongest associations were among persons taking >1.5 pills per day for at least 10 years (odds ratio, 4.27; 95% CI, 2.53−7.21). No similar strong associations were found for other commonly used prescription medications. Conclusions Among patients without known risk factors for iron deficiency, gastric acid inhibitor use for ≥2 years was associated with an increased subsequent risk of iron deficiency. The risk increased with increasing potency of acid inhibition and decreased after medication discontinuation.