TY - JOUR

T1 - Safety of Proton Pump Inhibitors Based on a Large, Multi-year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin

AU - Moayyedi, Paul

AU - Eikelboom, John W

AU - Bosch, Jackie

AU - Connolly, Stuart J

AU - Dyal, Leanne

AU - Shestakovska, Olga

AU - Leong, Darryl

AU - Anand, Sonia S

AU - Störk, Stefan

AU - Branch, Kelley R H

AU - Bhatt, Deepak L

AU - Verhamme, Peter B

AU - O'Donnell, Martin

AU - Maggioni, Aldo P

AU - Lonn, Eva M

AU - Piegas, Leopoldo S

AU - Ertl, Georg

AU - Keltai, Matyas

AU - Bruns, Nancy Cook

AU - Muehlhofer, Eva

AU - Dagenais, Gilles R

AU - Kim, Jae-Hyung

AU - Hori, Masatsugu

AU - Steg, P Gabriel

AU - Hart, Robert G

AU - Diaz, Rafael

AU - Alings, Marco

AU - Widimsky, Petr

AU - Avezum, Alvaro

AU - Probstfield, Jeffrey

AU - Zhu, Jun

AU - Liang, Yan

AU - Lopez-Jaramillo, Patricio

AU - Kakkar, Ajay K

AU - Parkhomenko, Alexander N

AU - Ryden, Lars

AU - Pogosova, Nana

AU - Dans, Antonio L

AU - Lanas, Fernando

AU - Commerford, Patrick J

AU - Torp-Pedersen, Christian

AU - Guzik, Tomek J

AU - Vinereanu, Dragos

AU - Tonkin, Andrew M

AU - Lewis, Basil S

AU - Felix, Camilo

AU - Yusoff, Khalid

AU - Metsarinne, Kaj P

AU - Fox, Keith A A

AU - Yusuf, Salim

AU - COMPASS Investigators

N1 - Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2019/9

Y1 - 2019/9

N2 - 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 3x2 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% CI, 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 identifier: NCT01776424 (https://clinicaltrials.gov/ct2/show/NCT01776424).

AB - 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 3x2 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% CI, 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 identifier: NCT01776424 (https://clinicaltrials.gov/ct2/show/NCT01776424).

KW - Bacteria

KW - CVD

KW - Reflux

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=85070685740&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2019.05.056

DO - 10.1053/j.gastro.2019.05.056

M3 - Journal article

VL - 157

SP - 682-691.e2

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -