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Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explo...

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Autores principales: Shah, Nigam H., LePendu, Paea, Bauer-Mehren, Anna, Ghebremariam, Yohannes T., Iyer, Srinivasan V., Marcus, Jake, Nead, Kevin T., Cooke, John P., Leeper, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462578/
https://www.ncbi.nlm.nih.gov/pubmed/26061035
http://dx.doi.org/10.1371/journal.pone.0124653
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author Shah, Nigam H.
LePendu, Paea
Bauer-Mehren, Anna
Ghebremariam, Yohannes T.
Iyer, Srinivasan V.
Marcus, Jake
Nead, Kevin T.
Cooke, John P.
Leeper, Nicholas J.
author_facet Shah, Nigam H.
LePendu, Paea
Bauer-Mehren, Anna
Ghebremariam, Yohannes T.
Iyer, Srinivasan V.
Marcus, Jake
Nead, Kevin T.
Cooke, John P.
Leeper, Nicholas J.
author_sort Shah, Nigam H.
collection PubMed
description BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches. METHODS: Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population. RESULTS: In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H(2) blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000. CONCLUSIONS: Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.
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spelling pubmed-44625782015-06-25 Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population Shah, Nigam H. LePendu, Paea Bauer-Mehren, Anna Ghebremariam, Yohannes T. Iyer, Srinivasan V. Marcus, Jake Nead, Kevin T. Cooke, John P. Leeper, Nicholas J. PLoS One Research Article BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches. METHODS: Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population. RESULTS: In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H(2) blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000. CONCLUSIONS: Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation. Public Library of Science 2015-06-10 /pmc/articles/PMC4462578/ /pubmed/26061035 http://dx.doi.org/10.1371/journal.pone.0124653 Text en © 2015 Shah et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shah, Nigam H.
LePendu, Paea
Bauer-Mehren, Anna
Ghebremariam, Yohannes T.
Iyer, Srinivasan V.
Marcus, Jake
Nead, Kevin T.
Cooke, John P.
Leeper, Nicholas J.
Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
title Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
title_full Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
title_fullStr Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
title_full_unstemmed Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
title_short Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population
title_sort proton pump inhibitor usage and the risk of myocardial infarction in the general population
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462578/
https://www.ncbi.nlm.nih.gov/pubmed/26061035
http://dx.doi.org/10.1371/journal.pone.0124653
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