Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus older agents.
OBJECTIVE
The relative gastrointestinal toxicity of NSAIDs in normal clinical practice is unknown. The aim of this study was to estimate the risk of upper gastrointestinal bleeding associated with NSAIDs and analgesics, with special emphasis on those agents that have been introduced in recent years.


METHODS
Multicentre case-control study.


METHODS
All incident community cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients aged >18 years of age (4309 cases). After secondary exclusions, 2813 cases and 7193 matched controls were included in the analysis.


METHODS
Eighteen hospitals in Spain and Italy with a total study experience of 10,734,897 person-years.


METHODS
Odds ratios of upper gastrointestinal bleeding for each drug, with adjustment for potential confounders. For each individual drug the reference category was defined as those not exposed to the drug.


RESULTS
The incidence of upper gastrointestinal bleeding was 401.4 per million inhabitants aged >18 years. Thirty-eight percent of cases were attributable to NSAIDs. Individual risks for each NSAID were dose dependent. Ketorolac was associated with the highest risk estimate (24.7; 95% CI 8.0, 77.0). For newer NSAIDs, the risks were as follows: aceclofenac 1.4 (95% CI 0.6, 3.3), celecoxib 0.3 (95% CI 0.03, 4.1), dexketoprofen 4.9 (95% CI 1.7, 13.9), meloxicam 5.7 (95% CI 2.2, 15.0), nimesulide 3.2 (95% CI 1.9, 5.6) and rofecoxib 7.2 (95% CI 2.3, 23.0). The risk was significantly increased in patients with a history of peptic ulcer and/or upper gastrointestinal bleeding, and in those taking antiplatelet drugs.


CONCLUSIONS
NSAID-induced upper gastrointestinal bleeding is a common cause of hospital admission. Apart from the patient's history of peptic ulcer, its risk depends on the particular drug and its dose, and on concomitant treatments. Our results do not confirm that greater selectivity for COX-2 confers less risk of upper gastrointestinal bleeding.
Laporte
Joan-Ramon
JR
Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain. jrl@icf.uab.es
Ibáñez
Luisa
L
Vidal
Xavier
X
Vendrell
Lourdes
L
Leone
Roberto
R
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal