Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782375683732799488 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4462578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT shahnigamh protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT lependupaea protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT bauermehrenanna protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT ghebremariamyohannest protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT iyersrinivasanv protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT marcusjake protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT neadkevint protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT cookejohnp protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation AT leepernicholasj protonpumpinhibitorusageandtheriskofmyocardialinfarctioninthegeneralpopulation |