Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.
Aged
Aspirin
/ administration & dosage
Cardiovascular Diseases
/ diagnosis
Double-Blind Method
Drug Administration Schedule
Enterocolitis, Pseudomembranous
/ chemically induced
Factor Xa Inhibitors
/ administration & dosage
Female
Gastrointestinal Hemorrhage
/ chemically induced
Humans
Male
Middle Aged
Pantoprazole
/ administration & dosage
Peripheral Arterial Disease
/ diagnosis
Platelet Aggregation Inhibitors
/ administration & dosage
Prospective Studies
Proton Pump Inhibitors
/ administration & dosage
Risk Assessment
Risk Factors
Rivaroxaban
/ administration & dosage
Time Factors
Treatment Outcome
Bacteria
CVD
Reflux
Thrombosis
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
18
03
2019
revised:
18
05
2019
accepted:
21
05
2019
pubmed:
4
6
2019
medline:
26
9
2019
entrez:
2
6
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31152740
pii: S0016-5085(19)40974-8
doi: 10.1053/j.gastro.2019.05.056
pii:
doi:
Substances chimiques
Factor Xa Inhibitors
0
Platelet Aggregation Inhibitors
0
Proton Pump Inhibitors
0
Rivaroxaban
9NDF7JZ4M3
Pantoprazole
D8TST4O562
Aspirin
R16CO5Y76E
Banques de données
ClinicalTrials.gov
['NCT01776424']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
682-691.e2Commentaires et corrections
Type : CommentIn
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Informations de copyright
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.