Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.

BACKGROUND: Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. METHODS AND FINDINGS: We conducted a population-based case-control study of multiple h...

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Main Authors: Jonathan Zipursky, Erin M Macdonald, Simon Hollands, Tara Gomes, Muhammad M Mamdani, J Michael Paterson, Nina Lathia, David N Juurlink
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-09-01
Series:PLoS Medicine
Online Access:http://europepmc.org/articles/PMC4181956?pdf=render
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author Jonathan Zipursky
Erin M Macdonald
Simon Hollands
Tara Gomes
Muhammad M Mamdani
J Michael Paterson
Nina Lathia
David N Juurlink
author_facet Jonathan Zipursky
Erin M Macdonald
Simon Hollands
Tara Gomes
Muhammad M Mamdani
J Michael Paterson
Nina Lathia
David N Juurlink
author_sort Jonathan Zipursky
collection DOAJ
description BACKGROUND: Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. METHODS AND FINDINGS: We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients. CONCLUSIONS: PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.
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spelling doaj.art-e764724d386f472d92f020b724f4e9cf2022-12-22T00:00:22ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762014-09-01119e100173610.1371/journal.pmed.1001736Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.Jonathan ZipurskyErin M MacdonaldSimon HollandsTara GomesMuhammad M MamdaniJ Michael PatersonNina LathiaDavid N JuurlinkBACKGROUND: Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. METHODS AND FINDINGS: We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients. CONCLUSIONS: PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.http://europepmc.org/articles/PMC4181956?pdf=render
spellingShingle Jonathan Zipursky
Erin M Macdonald
Simon Hollands
Tara Gomes
Muhammad M Mamdani
J Michael Paterson
Nina Lathia
David N Juurlink
Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
PLoS Medicine
title Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
title_full Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
title_fullStr Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
title_full_unstemmed Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
title_short Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
title_sort proton pump inhibitors and hospitalization with hypomagnesemia a population based case control study
url http://europepmc.org/articles/PMC4181956?pdf=render
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