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Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin
Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, Leong D, Anand SS et al.. Gastroenterology, 2019-05-29
Topic: Risk, prevention and care in population studies
Background & aims Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. Methods We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. Results There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. Conclusions In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
Key findings
- These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies.
- We aimed to confirm these findings in an adequately powered randomized trial.
- Results There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75).
- For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.
- Conclusions In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections.
Why it matters
In this large randomized trial, pantoprazole use was not linked to a significant difference in dementia or most other safety outcomes compared with placebo, except for a small increase in enteric infections. This means long-term use of this drug was not found to raise or lower dementia risk in this trial.
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Study details
- Study designrandomized controlled trial
- Participants8,791
- Effect size1.4%; 1.0%
- Evidence strengthHigh
How this study scored 81/100
Published in a peer-reviewed journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Gastroenterology) |
| Journal's citation record | 4 / 4 | Gastroenterology: journal h-index 586 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 8,791 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 483 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 53.7 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 6 / 6 | Cited 41.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 3 / 4 | Cited 157 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Salim Yusuf: h-index 262 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 45 institution(s) in 29 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31152740) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 81 / 100 | — |
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Read the original
- DOI: 10.1053/j.gastro.2019.05.056
- PubMed: 31152740
- Original source →
- Free full text: VBN Forskningsportal (Aalborg Universitet) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Moayyedi, P., Eikelboom, J. W., Bosch, J., Connolly, S. J., Dyal, L., Shestakovska, O., et al. (2019). Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. https://doi.org/10.1053/j.gastro.2019.05.056
Vancouver
Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. 2019. doi:10.1053/j.gastro.2019.05.056. PMID: 31152740.
BibTeX
@article{moayyedi2019-31152740,
author = {Moayyedi, P. and Eikelboom, J. W. and Bosch, J. and Connolly, S. J. and Dyal, L. and Shestakovska, O. and Leong, D. and Anand, S. S. and others},
title = {{Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin}},
journal = {Gastroenterology},
year = {2019},
doi = {10.1053/j.gastro.2019.05.056},
pmid = {31152740},
url = {https://doi.org/10.1053/j.gastro.2019.05.056}
}
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