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Gastroenterology. 2019 Aug;157(2):403-412.e5. doi: 10.1053/j.gastro.2019.04.041. Epub 2019 May 2.

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

Author information

1
The Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. Electronic address: moayyep@mcmaster.ca.
2
The Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
3
University of Philippines, Manila, Philippines.
4
University of Würzburg and University Hospital, Würzburg, Germany.
5
University of Washington Medical Center, Seattle, Washington.
6
Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts.
7
University of Leuven, Leuven, Belgium.
8
National University of Ireland, Galway, Ireland.
9
National Association of Hospital Cardiologists Research Center (ANMCO), Florence, Italy.
10
The Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada; Bayer, Leverkusen, Germany.
11
Hospital do Coracao, Sao Paulo, Brazil.
12
Semmelweis University, Budapest, Hungary.
13
Bayer, Leverkusen, Germany.
14
Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec, Canada.
15
Catholic University of Korea, Seoul, South Korea.
16
Osaka International Cancer Institute, Osaka, Japan.
17
Hopitaux de Paris, Paris, France.
18
Estudios Clinicos Latino America and Instituto Cardiovascular de Rosario, Rosario, Argentina.
19
Amphia Ziekenhuis and Werkgroep Cardiologische Centra Nederland (WCN), Utrecht, the Netherlands.
20
Cardiocenter, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
21
Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
22
University of Washington, Seattle, Washington.
23
FuWai Hospital, Beijing, China.
24
Research Institute, Fundaciun Oftalmoligica de Santander (FOSCAL)-Bucaramanga, Bucaramanga, Colombia.
25
Thrombosis Research Institute and University College London, London, UK.
26
Institute of Cardiology, Kiev, Ukraine.
27
Karolinska Institutet, Stockholm, Sweden.
28
National Research Center for Preventative Medicine, Moscow, Russia.
29
College of Medicine, University of the Philippines-Manila, Ermita, Manila, Philippines.
30
Universidad de La Frontera, Temuco, Chile.
31
University of Cape Town, Cape Town, South Africa.
32
University of Aalborg, Copenhagen, Denmark.
33
University of Glasgow, Glasgow, UK; Collegium Medicum Jagiellonian University, Krakow, Poland.
34
University of Medicine and Pharmacology, Carol Davila University and Emergency Hospital, Bucharest, Romania.
35
Monash University, Melbourne, Victoria, Australia.
36
Lady Davis Carmel Medical Center, Haifa, Israel.
37
Facultad de Ciencias de la Salud Eugenio Espejo-Universidad Tecnoligica Equinoccial, Quito, Ecuador.
38
Universiti Teknologi Mara, Selangor, Malaysia.
39
Universit Paris Diderot, Hopital Bichat, Assistance Publique, Paris, France; Turku University Central Hospital and Turku University, Turku, Finland.
40
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

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:

Drug; Heart Disease Prevention; Stomach; Thrombosis

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