Randomised controlled trialindependent cross-checkabstract checked★ key study I-PPI-102 in-depth review
Routine acid blocker gave small benefit in low-risk heart patients
Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial.
Overview
Moayyedi P et al.. Gastroenterology 2019 · PMID 31054846 · DOI 10.1053/j.gastro.2019.04.041
In 17,598 heart patients on aspirin or a blood thinner, pantoprazole halved bleeding from stomach lesions but did not reduce all stomach problems combined; about 1000 needed treatment to prevent one bleed.
Does the study support the specific claim? Partly · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test routine PPI in heart patients on blood thinners.
- How was the study done?
Double-blind RCT.
- How many people, animals or samples were studied?
17,598 patients.
- What was actually found?
No effect on composite; fewer bleeding lesions.
- How large was the observed effect?
HR 0.88 composite; 0.52 bleeding lesions.
- What do the results mean in everyday life?
Benefit depends on bleeding risk; low-risk people gain little.
- What are the study's limitations?
Low event rates.
- What does it say about Elawady's specific claim?
Supports reviewing 'protective' PPIs, contradicts a universal ban.
- Do the results apply to Germany and Europe?
Applies to Europe.
- What can explicitly not be concluded from this study?
Not about high-risk patients with prior bleeding.
Scientific in-depth review
1. Full reference
- Authors
- Moayyedi P et al.
- Journal
- Gastroenterology
- Year
- 2019
- Identifier
- PMID 31054846 DOI 10.1053/j.gastro.2019.04.041
- Verification
- verified – PubMed efetch 2026-10-26 + Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Non-US government support listed; full COI not in abstract
2. Research question
Does routine pantoprazole reduce upper GI events in patients receiving rivaroxaban and/or aspirin for stable cardiovascular disease?
3. Study design and population
- Study design
- Randomised controlled trial – Double-blind, placebo-controlled 3x2 partial factorial RCT (COMPASS, gastrointestinal outcomes)
- Population
Stable coronary or peripheral artery disease
- Country
International (multicentre)
- Period
Published 2019 (NCT01776424)
- Sample size
17,598
- Inclusion and exclusion criteria
COMPASS participants not requiring a PPI
4. Methods and endpoints
- Exposure / intervention
Pantoprazole 40 mg daily
- Comparator
Placebo
- Endpoints
Composite upper GI events (overt bleeding, bleeding lesion, occult bleeding, symptomatic ulcer/erosions, obstruction, perforation)
- Statistical methods
Cox regression
5. Actual results
- Results
Composite: 102/8791 vs 116/8807; HR 0.88 (0.67-1.15). Bleeding from gastroduodenal lesions HR 0.52 (0.28-0.94; P=.03); post-hoc definition HR 0.45 (0.27-0.74), NNT 982 (609-2528).
- Absolute risks
Composite 1.16% vs 1.32% (ARR 0.16 percentage points); NNT 982 for post-hoc bleeding lesion
- Authors' conclusion
Routine PPI in patients on low-dose anticoagulation and/or aspirin for stable CVD does not reduce upper GI events but may reduce bleeding from gastroduodenal lesions.
6. Strengths
- Large double-blind RCT
- Clinical endpoints
7. Weaknesses
- Low-risk population (people needing a PPI excluded)
- Low event rates; post-hoc analyses
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Well conducted; post-hoc definitions flagged by authors.
9. Assessment of the statistical interpretation
Recomputed crude RR 0.88 (0.68-1.15), ARR 0.16 points, NNT ~640 for the composite (stats/C-PPI-10_compass_gi_scally.py).
10. Relevance to the specific claim
Balanced: PPIs reduce bleeding from lesions even in this population, but in unselected low-risk users routine protection gives little absolute benefit - supporting de-prescribing in low-risk people, not a ban in high-risk people.
11. Independent contrary findings
High-risk populations (prior bleeding, dual antiplatelet) show larger benefit (I-PPI-08, I-PPI-101).
12. Transferability to Germany and Europe
Applicable.
13. Overall methodological judgement
Key nuance for both C-PPI-10 and C-PPI-11.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Benefit thresholds by risk.
15. Linked fact checks
- All acid-suppressing medicines (PPIs and H2 blockers) are permanently forbidden; heartburn should stop through the diet, not through drugs. – Studies contradicting or limiting the claim
- PPIs are widely prescribed without a real indication (for example by doctors of other specialties to 'protect the stomach') and are now sold freely. – Studies supporting the claim