Cohort studycited by the Tayebat archivefull text checked★ key study A-PPI-12 in-depth review
PPIs and death in US veterans
Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study.
Overview
Xie Y et al.. BMJ 2019 · PMID 31147311 · DOI 10.1136/bmj.l1580
PPI users had an estimated 45 more deaths per 1,000 over about 10 years than H2-blocker users.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Mortality with PPIs.
- How was the study done?
Veterans cohort.
- How many people, animals or samples were studied?
214,467 new users.
- What was actually found?
Small excess mortality association.
- How large was the observed effect?
45.20/1,000 over 10 years.
- What do the results mean in everyday life?
Use PPIs only when needed.
- What are the study's limitations?
Confounding; specific population.
- What does it say about Elawady's specific claim?
Partly supports.
- Do the results apply to Germany and Europe?
Moderate.
- What can explicitly not be concluded from this study?
That PPIs cause death.
Scientific in-depth review
1. Full reference
- Authors
- Xie Y, Bowe B, Yan Y, Xian H, Li T, Al-Aly Z
- Journal
- BMJ
- Year
- 2019
- Identifier
- PMID 31147311 DOI 10.1136/bmj.l1580 · PMC6538974
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- full text
- Conflicts of interest and funding
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
2. Research question
All-cause and cause-specific mortality associated with PPIs
3. Study design and population
- Study design
- Cohort study – Longitudinal new-user active-comparator cohort, US Department of Veterans Affairs
- Population
New users of PPIs or H2 blockers
- Country
USA
- Period
Cohort entry 2002–2004; follow-up up to 10 years
- Sample size
157,625 PPI; 56,842 H2 blockers
- Inclusion and exclusion criteria
New users with >90-day supply in first 180 days
4. Methods and endpoints
- Exposure / intervention
New PPI use
- Comparator
New H2-blocker use
- Endpoints
All-cause and cause-specific death (attributable deaths per 1,000)
- Statistical methods
IPTW, two-stage residual inclusion, cumulative incidence at 10 years, negative control outcomes
5. Actual results
- Results
45.20 excess deaths (28.20–61.40) per 1,000 PPI users; circulatory 17.47; neoplasms 12.94; infectious 4.20; genitourinary 6.25; CVD 15.48; CKD 4.19; in users without documented indication: CVD 22.91, CKD 4.74, upper GI cancer 3.12. No excess for negative control outcomes.
- Absolute risks
45.20 excess deaths per 1,000 users over up to 10 years (cumulative estimate; full text).
- Authors' conclusion
Taking PPIs is associated with a small excess of cause-specific mortality; heightened vigilance may be warranted.
6. Strengths
- Active comparator, new-user design
- Negative control outcomes
- Large sample
7. Weaknesses
- Older, white, male veterans
- Residual confounding and channelling bias acknowledged by authors
- Observational
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Authors acknowledge channelling bias and residual confounding might not be eliminated (full text).
9. Assessment of the statistical interpretation
Absolute excess estimated from adjusted cumulative incidence; vulnerable to confounding.
10. Relevance to the specific claim
11. Independent contrary findings
Brown 2021 (I-PPI-02) indicates residual confounding; COMPASS (I-PPI-01) no mortality difference.
12. Transferability to Germany and Europe
Moderate: veteran population differs from general European population.
13. Overall methodological judgement
Sophisticated but observational; the 45/1,000 figure should not be read as proven drug-caused deaths.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | partly correct but over-interpreted |
14. Open questions
Would RCT data with longer follow-up show any mortality effect?
15. Linked fact checks
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
US Veterans cohort: 45 excess deaths per 1,000 PPI users from cardiovascular, kidney and upper GI cancer causes (narrative: followed for five years).
- A. What was actually studied?
Mortality in new PPI vs H2-blocker users.
- B. What did the authors find?
45.20 excess deaths/1,000; graded with duration.
- C. What conclusions do the authors themselves draw?
Association; vigilance warranted.
- D. What does the archive derive from it?
Presented as deaths caused by PPIs; narrative states five years.
- E. Is this derivation scientifically justified?
Partly: number correct, but cumulative over up to 10 years, population specific, causality not established.
- Adequacy of the interpretation (by the archive)
- partly correct but over-interpreted