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.

Amphia Ziekenhuis and Werkgroep Cardiologische Centra Nederland Utrecht the Netherlands

Bayer Leverkusen Germany

Brigham and Women's Hospital Heart and Vascular Center Harvard Medical School Boston Massachusetts

Cardiocenter University Hospital Kralovske Vinohrady and 3rd Faculty of Medicine Charles University Prague Czech Republic

Catholic University of Korea Seoul South Korea

Centre for Cardiovascular Science University of Edinburgh Edinburgh UK

College of Medicine University of the Philippines Manila Ermita Manila Philippines

Estudios Clinicos Latino America and Instituto Cardiovascular de Rosario Rosario Argentina

Facultad de Ciencias de la Salud Eugenio Espejo Universidad Tecnoligica Equinoccial Quito Ecuador

FuWai Hospital Beijing China

Hopitaux de Paris Paris France

Hospital do Coracao Sao Paulo Brazil

Institut Universitaire de Cardiologie et de Pneumologie de Quebec Quebec Canada

Institute of Cardiology Kiev Ukraine

Instituto Dante Pazzanese de Cardiologia Sao Paulo Brazil

Karolinska Institutet Stockholm Sweden

Lady Davis Carmel Medical Center Haifa Israel

Monash University Melbourne Victoria Australia

National Association of Hospital Cardiologists Research Center Florence Italy

National Research Center for Preventative Medicine Moscow Russia

National University of Ireland Galway Ireland

Osaka International Cancer Institute Osaka Japan

Research Institute Fundaciun Oftalmoligica de Santander Bucaramanga Bucaramanga Colombia

Semmelweis University Budapest Hungary

The Population Health Research Institute McMaster University and Hamilton Health Sciences Hamilton Ontario Canada

The Population Health Research Institute McMaster University and Hamilton Health Sciences Hamilton Ontario Canada; Bayer Leverkusen Germany

Thrombosis Research Institute and University College London London UK

Universidad de La Frontera Temuco Chile

Universit Paris Diderot Hopital Bichat Assistance Publique Paris France; Turku University Central Hospital and Turku University Turku Finland

Universiti Teknologi Mara Selangor Malaysia

University of Aalborg Copenhagen Denmark

University of Cape Town Cape Town South Africa

University of Glasgow Glasgow UK; Collegium Medicum Jagiellonian University Krakow Poland

University of Leuven Leuven Belgium

University of Medicine and Pharmacology Carol Davila University and Emergency Hospital Bucharest Romania

University of Philippines Manila Philippines

University of Washington Medical Center Seattle Washington

University of Washington Seattle Washington

University of Würzburg and University Hospital Würzburg Germany

Ann Intern Med. 2019 Oct 15;171(8):JC45. doi: 10.7326/ACPJ201910150-045. PubMed

Gastroenterology. 2020 Jan;158(1):285-286. doi: 10.1053/j.gastro.2019.10.032. PubMed

Gastroenterology. 2020 Jan;158(1):283-284. doi: 10.1053/j.gastro.2019.08.063. PubMed

Gastroenterology. 2020 Jan;158(1):284-285. doi: 10.1053/j.gastro.2019.09.050. PubMed

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ClinicalTrials.gov
NCT01776424