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.

• Authors: 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
• Journal: Gastroenterology (Gastroenterology) Vol. 157 Issue 2 Pg. 403-412.e5 (08 2019) ISSN: 1528-0012 [Electronic] United States
• PMID: 31054846 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticoagulants
• Proton Pump Inhibitors
• Rivaroxaban
• Pantoprazole
• Aspirin

Topics

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