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Only full adherence to proton pump inhibitors protects against drug-induced upper gastrointestinal bleeding

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The use of gastroprotective agents has allowed significant progress in the prevention of upper gastrointestinal bleeding (UGIB) associated with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents. Nevertheless, some concerns remain regarding the gastroprotective dosage and treatment duration. Our aim was to study the effect of gastroprotective agents in UGIB induced by NSAIDs and single- or dual-antiplatelet therapy.

Methods

A multicenter case-control study was conducted including 577 cases diagnosed with UGIB and 1343 sex-, age-, and hospital-matched controls. To estimate exposure to NSAIDs and gastroprotective agents, consumption was calculated for the 4 weeks prior to hospital admission in terms of defined daily doses (DDDs). Risk groups for UGIB induced by NSAIDs and single- or dual-antiplatelet therapy were defined as a function of each drug dose, use of gastrointestine-damaging drugs, and risk factors for UGIB. Odds ratios (ORs) with 95% confidence intervals (CIs) were adjusted for single- (model 1) and dual- (model 2) antiplatelet therapy.

Results

Full adherence (> 0.80DDD) to proton pump inhibitors (PPIs) was the only gastroprotective therapy that significantly reduced the risk of UGIB, considering NSAID risk (OR: 0.53; 95% CI: 0.30–0.95) and dose (OR: 0.48; 95% CI: 0.27–0.87) with ORs adjusted for single-antiplatelet therapy (model 1) and NSAID risk (OR: 0.55; 95% CI: 0.31–0.98) and dose (OR: 0.49; 95% CI: 0.28–0.89) with ORs adjusted for dual-antiplatelet therapy (model 2).

Conclusions

These results reinforce the recommendation of adding a PPI at effective doses (full adherence) to prevent UGIB induced by NSAIDs, or single- or dual-antiplatelet therapy.

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Guarantor of the article

C Aguirre and B Ruiz.

Funding

In Spain, this study was funded by the national Health Research Fund (Fondo de Investigación Sanitaria) (Ministry of Economy and Competitiveness), grant numbers PI 02/1512, 02/0661/, 02/1364, and 02/1572 and by the Department of Health of the Basque Country, grant numbers 03/11092 and 11/111103; as well as supported in part in Catalonia by the Novartis, Pfizer and Dr. Esteve pharmaceutical companies. In Italy, the study was funded by unrestricted grants from Pfizer Italy and Department of Medicine and Public Health, University of Verona. The funders had no role in the study design, data-collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Unidad de Farmacovigilancia del Pais Vasco, Galdakao-Usansolo Hospital, Barrio Labeaga 46A, 48960, Galdakao, Spain

    Borja Ruiz & Carmelo Aguirre

  2. Research Unit, Research Network of Health Services in Chronic Diseases (REDISSEC), Galdakao-Usansolo Hospital, Galdakao, Spain

    Urko Aguirre

  3. Department of Preventive Medicine and Public Health, Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública–CIBERESP), University of Santiago de Compostela, Santiago de Compostela, Spain

    Ana Estany-Gestal & Adolfo Figueiras

  4. 1st Department of Surgery, Surgical Endoscopy Unit, University of Verona, Verona, Italy

    Luca Rodella

  5. Department of Digestive Diseases, Basurto University Hospital, Bilbao, Spain

    Pablo Ruiz

  6. Pharmacoepidemiology Institute, Department of Pharmacology, School of Medicine, University of Valladolid, Valladolid, Spain

    Alfonso Carvajal & Luis H. Martin

  7. Catalan Institute of Pharmacology, Clinical Pharmacology Service, University Hospital Vall d’Hebron, Department of Pharmacology, Therapeutics and Toxicology, Autonomous University, Barcelona, Spain

    Luisa Ibáñez & Xavier Vidal

  8. Clinical Pharmacology Unit, Department of Medicine and Public Health, University of Verona, Verona, Italy

    Anita Conforti

  9. General Service of Genomic Research: DNA Bank, School of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain

    Marian M. de Pancorbo

  10. Pharmacology Department, School of Medicine and Nursing, University of the Basque Country, Leioa, Spain

    Carmelo Aguirre

Authors
  1. Borja Ruiz
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  2. Urko Aguirre
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  3. Ana Estany-Gestal
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  5. Pablo Ruiz
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  6. Adolfo Figueiras
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  7. Alfonso Carvajal
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  8. Luisa Ibáñez
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  10. Marian M. de Pancorbo
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  11. Xavier Vidal
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  12. Luis H. Martin
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  13. Carmelo Aguirre
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Contributions

A Figueiras, A Carvajal, L Ibañez, A Conforti, and C Aguirre: design of the research study, obtained funding; critical revision of the manuscript for important intellectual content. B Ruiz, A Estany-Gestal, L Rodella, P Ruiz: acquisition of data. B Ruiz, U Aguirre, C Aguirre: statistical analysis. B Ruiz and C Aguirre: drafting of the manuscript. MM de Pancorbo, X Vidal, and LH Martin: critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Carmelo Aguirre.

Ethics declarations

The study protocol was approved by the institutional review boards of all participating hospitals. All patients were provided with information about the study and gave written informed consent.

Conflict of interests

The authors declare that they have no conflict of interest.

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Ruiz, B., Aguirre, U., Estany-Gestal, A. et al. Only full adherence to proton pump inhibitors protects against drug-induced upper gastrointestinal bleeding. Eur J Clin Pharmacol 74, 1503–1511 (2018). https://doi.org/10.1007/s00228-018-2523-4

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  • DOI: https://doi.org/10.1007/s00228-018-2523-4

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