Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial

Paul Moayyedi; John W Eikelboom; Jackie Bosch; Stuart J Connolly; Leanne Dyal; Olga Shestakovska; Darryl Leong; Sonia S Anand; Stefan Störk; Kelly R H Branch; Deepak L Bhatt; Peter B Verhamme; Martin O'Donnell; Aldo P Maggioni; Eva M Lonn; Leopoldo S Piegas; Georg Ertl; Matyas Keltai; Nancy Cook Bruns; Eva Muehlhofer; Gilles R Dagenais; Jae-Hyung Kim; Masatsugu Hori; P Gabriel Steg; Robert G Hart; Rafael Diaz; Marco Alings; Petr Widimsky; Alvaro Avezum; Jeffrey Probstfield; Jun Zhu; Yan Liang; Patricio Lopez-Jaramillo; Ajay Kakkar; Alexander N Parkhomenko; Lars Ryden; Nana Pogosova; Antonio Dans; Fernando Lanas; Patrick J Commerford; Christian Torp-Pedersen; Tomek Guzik; Dragos Vinereanu; Andrew M Tonkin; Basil S Lewis; Camilo Felix; Khalid Yusoff; Kaj Metsarinne; Keith A A Fox; Salim Yusuf; COMPASS Investigators

doi:10.1053/j.gastro.2019.04.041

Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial

Paul Moayyedi, John W Eikelboom, Jackie Bosch, Stuart J Connolly, Leanne Dyal, Olga Shestakovska, Darryl Leong, Sonia S Anand, Stefan Störk, Kelly R H Branch, Deepak L Bhatt, Peter B Verhamme, Martin O'Donnell, Aldo P Maggioni, Eva M Lonn, Leopoldo S Piegas, Georg Ertl, Matyas Keltai, Nancy Cook Bruns, Eva MuehlhoferGilles R Dagenais, Jae-Hyung Kim, Masatsugu Hori, P Gabriel Steg, Robert G Hart, Rafael Diaz, Marco Alings, Petr Widimsky, Alvaro Avezum, Jeffrey Probstfield, Jun Zhu, Yan Liang, Patricio Lopez-Jaramillo, Ajay Kakkar, Alexander N Parkhomenko, Lars Ryden, Nana Pogosova, Antonio Dans, Fernando Lanas, Patrick J Commerford, Christian Torp-Pedersen, Tomek Guzik, Dragos Vinereanu, Andrew M Tonkin, Basil S Lewis, Camilo Felix, Khalid Yusoff, Kaj Metsarinne, Keith A A Fox, Salim Yusuf, COMPASS Investigators

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.

METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.

RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).

CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

Original language	English
Journal	Gastroenterology
Volume	157
Issue number	2
Pages (from-to)	403-412.e5
ISSN	0016-5085
DOIs	https://doi.org/10.1053/j.gastro.2019.04.041
Publication status	Published - Aug 2019

Keywords

Administration, Oral
Aged
Anticoagulants/administration & dosage
Aspirin/administration & dosage
Cardiovascular Diseases/prevention & control
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination/adverse effects
Female
Gastrointestinal Hemorrhage/chemically induced
Humans
Male
Middle Aged
Pantoprazole/administration & dosage
Peptic Ulcer/chemically induced
Proton Pump Inhibitors/administration & dosage
Rivaroxaban/administration & dosage
Treatment Outcome

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Moayyedi, P., Eikelboom, J. W., Bosch, J., Connolly, S. J., Dyal, L., Shestakovska, O., Leong, D., Anand, S. S., Störk, S., Branch, K. R. H., Bhatt, D. L., Verhamme, P. B., O'Donnell, M., Maggioni, A. P., Lonn, E. M., Piegas, L. S., Ertl, G., Keltai, M., Cook Bruns, N., ... COMPASS Investigators (2019). Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial. Gastroenterology, 157(2), 403-412.e5. https://doi.org/10.1053/j.gastro.2019.04.041

@article{a5d523df1c2045db9849cfdb06f19b9f,

title = "Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial",

abstract = "BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.",

keywords = "Administration, Oral, Aged, Anticoagulants/administration & dosage, Aspirin/administration & dosage, Cardiovascular Diseases/prevention & control, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination/adverse effects, Female, Gastrointestinal Hemorrhage/chemically induced, Humans, Male, Middle Aged, Pantoprazole/administration & dosage, Peptic Ulcer/chemically induced, Proton Pump Inhibitors/administration & dosage, Rivaroxaban/administration & dosage, Treatment Outcome",

author = "Paul Moayyedi and Eikelboom, {John W} and Jackie Bosch and Connolly, {Stuart J} and Leanne Dyal and Olga Shestakovska and Darryl Leong and Anand, {Sonia S} and Stefan St{\"o}rk and Branch, {Kelly R H} and Bhatt, {Deepak L} and Verhamme, {Peter B} and Martin O'Donnell and Maggioni, {Aldo P} and Lonn, {Eva M} and Piegas, {Leopoldo S} and Georg Ertl and Matyas Keltai and {Cook Bruns}, Nancy and Eva Muehlhofer and Dagenais, {Gilles R} and Jae-Hyung Kim and Masatsugu Hori and Steg, {P Gabriel} and Hart, {Robert G} and Rafael Diaz and Marco Alings and Petr Widimsky and Alvaro Avezum and Jeffrey Probstfield and Jun Zhu and Yan Liang and Patricio Lopez-Jaramillo and Ajay Kakkar and Parkhomenko, {Alexander N} and Lars Ryden and Nana Pogosova and Antonio Dans and Fernando Lanas and Commerford, {Patrick J} and Christian Torp-Pedersen and Tomek Guzik and Dragos Vinereanu and Tonkin, {Andrew M} and Lewis, {Basil S} and Camilo Felix and Khalid Yusoff and Kaj Metsarinne and Fox, {Keith A A} and Salim Yusuf and {COMPASS Investigators}",

year = "2019",

month = aug,

doi = "10.1053/j.gastro.2019.04.041",

language = "English",

volume = "157",

pages = "403--412.e5",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "Elsevier",

number = "2",

}

Moayyedi, P, Eikelboom, JW, Bosch, J, Connolly, SJ, Dyal, L, Shestakovska, O, Leong, D, Anand, SS, Störk, S, Branch, KRH, Bhatt, DL, Verhamme, PB, O'Donnell, M, Maggioni, AP, Lonn, EM, Piegas, LS, Ertl, G, Keltai, M, Cook Bruns, N, Muehlhofer, E, Dagenais, GR, Kim, J-H, Hori, M, Steg, PG, Hart, RG, Diaz, R, Alings, M, Widimsky, P, Avezum, A, Probstfield, J, Zhu, J, Liang, Y, Lopez-Jaramillo, P, Kakkar, A, Parkhomenko, AN, Ryden, L, Pogosova, N, Dans, A, Lanas, F, Commerford, PJ, Torp-Pedersen, C, Guzik, T, Vinereanu, D, Tonkin, AM, Lewis, BS, Felix, C, Yusoff, K, Metsarinne, K, Fox, KAA, Yusuf, S & COMPASS Investigators 2019, 'Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial', Gastroenterology, vol. 157, no. 2, pp. 403-412.e5. https://doi.org/10.1053/j.gastro.2019.04.041

TY - JOUR

T1 - Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial

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, Kelly 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 - Cook Bruns, Nancy

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

AU - Parkhomenko, Alexander N

AU - Ryden, Lars

AU - Pogosova, Nana

AU - Dans, Antonio

AU - Lanas, Fernando

AU - Commerford, Patrick J

AU - Torp-Pedersen, Christian

AU - Guzik, Tomek

AU - Vinereanu, Dragos

AU - Tonkin, Andrew M

AU - Lewis, Basil S

AU - Felix, Camilo

AU - Yusoff, Khalid

AU - Metsarinne, Kaj

AU - Fox, Keith A A

AU - Yusuf, Salim

AU - COMPASS Investigators

PY - 2019/8

Y1 - 2019/8

N2 - BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

AB - BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

KW - Administration, Oral

KW - Aged

KW - Anticoagulants/administration & dosage

KW - Aspirin/administration & dosage

KW - Cardiovascular Diseases/prevention & control

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Therapy, Combination/adverse effects

KW - Female

KW - Gastrointestinal Hemorrhage/chemically induced

KW - Humans

KW - Male

KW - Middle Aged

KW - Pantoprazole/administration & dosage

KW - Peptic Ulcer/chemically induced

KW - Proton Pump Inhibitors/administration & dosage

KW - Rivaroxaban/administration & dosage

KW - Treatment Outcome

U2 - 10.1053/j.gastro.2019.04.041

DO - 10.1053/j.gastro.2019.04.041

M3 - Journal article

C2 - 31054846

SN - 0016-5085

VL - 157

SP - 403-412.e5

JO - Gastroenterology

JF - Gastroenterology

IS - 2

ER -

Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial

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Keywords

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