ArticlePloS one2015
Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 9 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
127 citing papers in PubMed, 9 syntheses or guidelines pooled it, 335 citations in OpenAlex.
- Proton pump inhibitor use: systematic review of global trends and practices.European journal of clinical pharmacology · 2023Pooled it
- Esomeprazole covalently interacts with the cardiovascular enzyme dimethylarginine dimethylaminohydrolase: Insights into the cardiovascular risk of proton pump inhibitors.Biochimica et biophysica acta. General subjects · 2022Pooled it
- The need of a multicomponent guiding approach to personalize clopidogrel treatment.The pharmacogenomics journal · 2021Pooled it
- [Clinical Guidelines for Drug-induced Peptic Ulcer, 2020 Revised Edition].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2020Guideline
- Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials.The lancet. Gastroenterology & hepatology · 2018Pooled it
- Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis.World journal of gastroenterology · 2017Pooled it
- Guideline
- Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.Journal of managed care & specialty pharmacy · 2016Pooled it
- Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.Journal of the American Heart Association · 2015Pooled it
- Trial
- Ameliorating Effects of Transcutaneous Electrical Acustimulation Combined With Deep Breathing Training on Refractory Gastroesophageal Reflux Disease Mediated via the Autonomic Pathway.Neuromodulation : journal of the International Neuromodulation Society · 2019Trial
- Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan.PloS one · 2017Trial
- Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: long-term 3-year results.Surgical endoscopy · 2016Trial
- A gene therapy approach to prevent dilated intercellular space, a hallmark of gastroesophageal reflux disease.Gene therapy · 2026Article
- Causal knowledge graph analysis identifies adverse drug effects.Bioinformatics (Oxford, England) · 2026Article
- Appropriate Use of Proton Pump Inhibitors in Older Adults: Concerns and Solutions.Drugs & aging · 2026Review
- Proton Pump Inhibitors and Biomarkers of Haemostasis in Postmenopausal Women: The Buffalo OsteoPerio Study.Basic & clinical pharmacology & toxicology · 2026Article
- Proton pump inhibitor use and cardiovascular risk, all-cause, and cardiovascular mortality across baseline eGFR categories: a longitudinal study.Renal failure · 2025Article
- Longitudinal trajectories unravel the complex interplay of medication, cardiovascular events, chronic kidney disease, and mortality.Scientific reports · 2025Article
- Gastroesophageal Reflux Disease (GERD) and Risk of Incident Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Cohort Studies.JGH open : an open access journal of gastroenterology and hepatology · 2025Review
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsProton 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.
methodsUsing 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.
resultsIn 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 H2 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.
conclusionsConsistent 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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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.