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Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations
  1. A Lanas1,
  2. L A García-Rodríguez2,
  3. M T Arroyo1,
  4. F Gomollón3,
  5. F Feu4,
  6. A González-Pérez2,
  7. E Zapata5,
  8. G Bástida6,
  9. L Rodrigo7,
  10. S Santolaria8,
  11. M Güell9,
  12. C M de Argila10,
  13. E Quintero11,
  14. F Borda12,
  15. J M Piqué4,
  16. on behalf of the Investigators of the Asociación Española de Gastroenterología (AEG)
  1. 1Servicio de Aparato Digestivo, Hospital Clínico Zaragoza, Zaragoza, Spain
  2. 2Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain
  3. 3Servicio de Aparato Digestivo, Hospital Miguel Server, Zaragoza, Spain
  4. 4Servicio de Gastroenterología, Hospital Clínic, Barcelona, Spain
  5. 5Servicio de Aparato Digestivo, Hospital Donostia, San Sebastian, Spain
  6. 6Servicio de Aparato Digestivo Hospital La Fe, Valencia, Spain
  7. 7Servicio de Aparato Digestivo, Hospital de Asturias, Oviedo, Spain
  8. 8Servicio de Aparato Digestivo, Hospital San Jorge, Huesca, Spain
  9. 9Servicio de Aparato Digestivo, Hospital de Sabadell, Barcelona, Spain
  10. 10Servicio de Aparato Digestivo, Hospital Ramón y Cajal, Madrid, Spain
  11. 11Servicio de Aparato Digestivo, Hospital Universitario de la Laguna, Tenerife, Spain
  12. 12Servicio de Aparato Digestivo, Hospital de Navarra, Pamplona, Spain
  1. Correspondence to:
    A Lanas
    Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza 50009, Spain; alanas{at}


Background: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate.

Objective: To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice.

Methods: A hospital-based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided.

Results: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way.

Conclusions: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.

  • COX, cyclo-oxygenase
  • NSAIDs, non-steroidal anti-inflammatory drugs
  • PPI, proton pump inhibitor
  • UGIB, upper gastrointestinal bleeding

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  • Published Online First 10 May 2006

  • Funding: This study was made possible by funds from grant C03/02 from the National Institute of Research Carlos III and by unrestricted grants provided by Pfizer Spain, Merck Spain, AstraZeneca Spain, Uriach Laboratories and Rottapharm to the Spanish Association of Gastroenterology (AEG). These contributors have not had a role in the conduction of the study, the interpretation of data or writing of the manuscript.

  • Dr Angel Lanas coordinated the study and contributed to the analysis and interpretation of data. Dr Lanas and Dr Luis Alberto García Rodríguez designed the study and drafted the manuscript. Dr Luis Alberto García Rodríguez carried out the statistical analysis of data and contributed to the analysis and interpretation of data. Dr Maria T Arroyo coordinated the collection of data between collaborating hospitals. All investigators made major contributions to the collection of data, revised data interpretation and had the opportunity to revise the manuscript. This study was presented at the plenary session of the last American Gastroenterological Association meeting.