SynthesisBMC medicine2021
Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials.
Synthesis in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 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
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Meta-analysis and Mendelian randomization study on the association between exposure to chlorinated disinfection byproducts and preterm birth risk.Journal of perinatology : official journal of the California Perinatal Association · 2025Pooled it
- Risk of stroke associated with proton pump inhibitor use among individuals with and without pre-existing cardiovascular diseases: a systematic review and meta-analysis.Journal of cardiothoracic surgery · 2025Pooled it
- Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.BMC cardiovascular disorders · 2024Pooled it
- Impact of Proton Pump Inhibitor Use on Outcomes Following Carotid Artery Stenting for Asymptomatic Carotid Stenosis: A Population-Based Cohort Study.The Kaohsiung journal of medical sciences · 2026Article
- Diagnostic and prognostic value of combined adiponectin, D-dimer, and Framingham Stroke Profilein patients with isolated vertigo and concurrent cerebral infarction.American journal of translational research · 2026Article
- 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
- Association between acid-suppressant use and self-reported stroke.BMC neurology · 2025Article
- Associations of digestive diseases exposure and lifestyle factors with Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Proton Pump Inhibitors Use in Patients With Ischemic Stroke on Dual Antiplatelet Therapy at Low Risk of Upper Gastrointestinal Bleeding.Journal of the American Heart Association · 2025Article
- Proton pump inhibitors and gut microbiota dysbiosis: insights into the pathogenesis of ulcerative colitis.Frontiers in microbiology · 2025Article
- Proton pump inhibitor use and risk of stroke: A systematic review and meta-analysis.Pakistan journal of medical sciences · 2024Review
- Individualized prevention of proton pump inhibitor related adverse events by risk stratification.Nature communications · 2024Article
- Proton pump inhibitors and dementia: A nationwide population-based study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Association between the Use of Proton Pump Inhibitors and Cardiovascular Diseases: A Nested Case-Control Study Using a National Health Screening Cohort.Biomedicines · 2024Article
- Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors.Chonnam medical journal · 2023Review
- Effect of methylenetetrahydrofolate reductase C677T polymorphism on serum folate but not vitamin B12 levels in patients with H-type hypertension.Molecular biology reports · 2022Article
- Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank.Frontiers in pharmacology · 2022Article
- Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundAlthough randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk.
methodsThis is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method).
resultsWe documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively.
conclusionsRegular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.
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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 Socratic graph.