Gastroenterology

Gastroenterology

Volume 152, Issue 4, March 2017, Pages 821-829.e1
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency

https://doi.org/10.1053/j.gastro.2016.11.023Get rights and content

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.

Section snippets

Study Population

We conducted a nested case-control study within the Kaiser Permanente, Northern California (KPNC) health care system, which provides comprehensive services to approximately 3.7 million members. The KPNC membership approximates the underlying census race/ethnicity and socioeconomic distributions of the region.13 Prescription drug benefits are utilized by >90% of members; databases electronically record dispense dates, dose, amount, directions for use, days supply, and refills for all

Results

We identified 334,683 members with an incident diagnosis of iron deficiency between January 1, 1999 and December 31, 2013. We excluded the following subjects: potential cases lacking matched controls (n = 59); potential cases (n = 225,779) and controls with the listed exclusion conditions; cases (n = 7321) and controls who received <2 years supply of PPIs or H2RAs; cases (n = 14) and controls who, despite having been dispensed ≥2 years supply of PPIs or H2RAs had taken them for <2 years of

Discussion

In the present study, the use of acid-inhibiting medications for at least 2 years was associated with a subsequent new diagnosis of iron deficiency. The magnitude of the association was stronger among younger age groups, with more potent acid suppression (PPIs vs H2RAs) and for higher doses of PPIs, and weaker after discontinuation of use. Differences were primarily found with transitions from no exposure to lower potency (H2RA) medications, from lower potency to higher potency medications

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    Conflicts of interest This author discloses the following: Douglas A. Corley has received funding from Pfizer. The remaining authors disclose no conflicts.

    Funding This work was supported by a Kaiser Permanente Community Benefits Grant. The funding source had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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