Risk of upper gastrointestinal ulcer bleeding associated with selective COX-2 inhibitors, traditional non-aspirin NSAIDs, aspirin, and combinations

Angel Lanas ^1*, Luis-Alberto García-Rodríguez ², Maria-Teresa Arroyo ¹, Fernando Gomollón ³, Faust Feu ⁴, Antonio González Pérez ², Eva Zapata ⁵, Guillermo Bástida ⁶, Luis Rodrigo ⁷, Santos Santolaria ⁸, Mercedes Güell ⁹, Carlos Martin de Argila ¹⁰, Enrique Quintero ¹¹, Fernando Borda ¹² and Jose María Piqué ⁴

¹ University Hospital, Zaragoza, Spain
² Centro Español de Farmacoepidemiológica, Madrid, Spain
³ Hospital Miguel Servet, Zaragoza, Spain
⁴ Hospital Clínic, Barcelona, Spain
⁵ Hospital Donostia, San Sebastian, Spain
⁶ Hospital La Fe, Valencia, Spain
⁷ Hospital de Asturias, Oviedo, Spain
⁸ Hospital San Jorge, Huesca, Spain
⁹ Hospital de Sabadell, Barcelona, Spain
¹⁰ Hospital Ramón y Cajal, Madrid, Spain
¹¹ Hospital Universitario de la Laguna, Tenerife, Spain
¹² Hospital de Navarra, Pamplona, Spain

^* To whom correspondence should be addressed. E-mail: alanas{at}unizar.es.

Accepted 17 April 2006

Abstract

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: We carried out a hospital-based, case- controlled study in the general community of patients from the National Health System in Spain. The study included 2,777 consecutive cases with endoscopy-proven major UGIB due to peptic lesions and 5,532 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: Non-aspirin-NSAID use increased the risk of UGIB (adj.RR: 5.3;95%CI 4.5-6.2). Among non-aspirin- NSAIDs, aceclofenac (adj.RR: 3.1;2.3-4.2) had the lowest RR, whereas ketorolac (adj.RR:14.4;5.2-39.9) had the highest. Rofecoxib therapy increased the risk of UGIB (adj.RR:2.1;1.1-4.0), whereas celecoxib, paracetamol or concomitant use of a PPI with an NSAID presented no increased risk. Non-aspirin antiplatelet therapy (clopidogrel/ticlopidine) had a similar risk of UGIB (adj.RR:2.8;1.9-4.2) to cardioprotective aspirin at a dose of 100 mg/daily (adj.RR:2.7;2.0-3.6) or anticoagulants (adj.RR:2.8;2.1-3.7). There was an apparent interaction between low-dose aspirin and use of either 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 Therapy with either non-aspirin antiplatelet therapy or cardioprotective aspirin has a similar risk of UGIB.

Keywords: COX-2 selective inhibitors, NSAIDs, aspirin, gastrointestinal bleeding, peptic ulcer

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