ArticleOpen heart
Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis.
Article in Open heart. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 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
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- Meta-Analysis of Efficacy and Safety of Proton Pump Inhibitors with Dual Antiplatelet Therapy for Coronary Artery Disease.Cardiovascular revascularization medicine : including molecular interventions · 2019Pooled it
- Guideline
- Trial
- Assessing Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Incidence of Major Adverse Cardiovascular Events: A Retrospective Cohort Study.Pharmacoepidemiology and drug safety · 2025Article
- Risk of Ischaemic Stroke Varies With Antithrombotic Drugs Use in Proton Pump Inhibitor Users: A Self-Controlled Case Series Study.Pharmacoepidemiology and drug safety · 2025Article
- Non-Variceal Upper Gastrointestinal Bleeding: A Retrospective Cohort of 364 Cases, Historical Comparison, and Updated Management Algorithm.Life (Basel, Switzerland) · 2025Article
- Observational
- Association between the Use of Proton Pump Inhibitors and Cardiovascular Diseases: A Nested Case-Control Study Using a National Health Screening Cohort.Biomedicines · 2024Article
- Proton pump inhibitor prescribing patterns and utilization: A retrospective chart review analysis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view.World journal of cardiology · 2023Review
- The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis.Journal of clinical medicine · 2022Review
- The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention.Frontiers in cardiovascular medicine · 2022Article
- Intermittent concurrent use of clopidogrel and proton pump inhibitors did not increase risk of adverse clinical outcomes in Chinese patients with coronary artery disease.BMC cardiovascular disorders · 2021Article
- Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Bare Metal Stent Implantation: A Nationwide Cohort Study.Acta Cardiologica Sinica · 2019Article
- Consensus Document ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: Long-term Antiplatelet Therapy in Patients with Coronary Artery Disease.European heart journal supplements : journal of the European Society of Cardiology · 2018Article
- Clinical Implications of Emerging Data on the Safety of Proton Pump Inhibitors.Current treatment options in gastroenterology · 2017Review
- Risk of acute myocardial infarction in patients with gastroesophageal reflux disease: A nationwide population-based study.PloS one · 2017Article
- Comparison of prophylactic effect of UGIB and effects on platelet function between PPIs and HTherapeutics and clinical risk management · 2017Article
- Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression.BMC medicine · 2016Review
- How May Proton Pump Inhibitors Impair Cardiovascular Health?American journal of cardiovascular drugs : drugs, devices, and other interventions · 2016Review
Corrections and comments
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Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs.
methodsWe systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I(2) statistics; p values inferior to 0.10 and I(2) >25% were considered significant for heterogeneity.
resultsWe included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding.
conclusionsThe results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.
Identifiers
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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.