Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs

• Published in: BMJ Vol. 325; no. 7365; pp. 624 - 627
• Main Authors: Mamdani, Muhammad, Rochon, Paula A, Juurlink, David N, Kopp, Alex, Anderson, Geoffrey M, Naglie, Gary, Austin, Peter C, Laupacis, Andreas
• Format: Journal Article
• Language: English
• Published: London British Medical Journal Publishing Group 21.09.2002; British Medical Association; BMJ Publishing Group Ltd; BMJ Publishing Group LTD; BMJ Publishing Group; BMJ
• Edition: International edition
• Subjects: Aged; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Biological and medical sciences; Celecoxib; Cohort Studies; Complications and side effects; Control groups; COX-2 inhibitors; Cyclooxygenase 2; Diclofenac - adverse effects; Drug Combinations; Drug prescriptions; Drug therapy; Drug toxicity and drugs side effects treatment; Female; Follow-Up Studies; Gastrointestinal agents; Gastrointestinal bleeding; Gastrointestinal hemorrhage; Gastrointestinal Hemorrhage - chemically induced; Hemorrhage; Hospitalization; Hospitalization - statistics & numerical data; Humans; Isoenzymes - antagonists & inhibitors; Lactones - adverse effects; Male; Medical disorders; Medical sciences; Membrane Proteins; Misoprostol - adverse effects; Multivariate Analysis; Nonsteroidal anti-inflammatory agents; Nonsteroidal anti-inflammatory drugs; Nonsteroidal antiinflammatory agents; Observational studies; Older adults; Pharmaceuticals; Pharmacology. Drug treatments; Prescription drugs; Proportional Hazards Models; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Risk Factors; Small intestine; Stomach; Sulfonamides - adverse effects; Sulfones; Toxicity: digestive system; Canada; Prostaglandin-endoperoxide synthase; Rofecoxib; Isozyme; Toxicity; Cardiovascular disease; Gastrointestinal; Epidemiology; Hemorrhage; Misoprostol; Diclofenac; Vascular disease; Cohort study; Intestinal disease; Gastric disease; Human; Enzyme; Enzyme inhibitor; Celecoxib; Non steroidal antiinflammatory agent; Arylacetic acid derivatives; Digestive diseases; Oxidoreductases; Elderly; Comparative study; Prostaglandin derivatives
• ISSN: 0959-8138; 0959-8146; 1756-1833; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.325.7365.624

Abstract Objective: To compare rates of upper gastrointestinal haemorrhage among elderly patients given selective cyclo-oxygenase-2 (COX 2) inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Design: Observational cohort study. Setting: Administrative data from Ontario, Canada, used from 17 April 2000 to 31 March 2001 to identify population based, NSAID-naive cohorts of patients. Patients: Subjects aged ≥ 66 years who started taking non-selective NSAIDs (n=5391), diclofenac plus misoprostol (n=5087), rofecoxib (n=14 583), or celecoxib (n=18 908) and a randomly selected control cohort not exposed to NSAIDs (n=100 000). Main outcome measures: Rate ratios of hospital admission for upper gastrointestinal haemorrhage in each drug cohort with adjustment for potential confounders. Results: Relative to controls, the multivariate model revealed an increased short term risk of upper gastrointestinal haemorrhage for users of non-selective NSAIDs (adjusted rate ratio 4.0 (95% confidence intervals 2.3 to 6.9)), diclofenac plus misoprostol (3.0 (1.7 to 5.6)), and rofecoxib (1.9 (1.3 to 2.8)) but not celecoxib (1.0 (0.7 to 1.6)). Relative to celecoxib, significantly higher risks of upper gastrointestinal haemorrhage were observed for non-selective NSAIDs (4.4 (2.3 to 8.5)), diclofenac plus misoprostol (3.2 (1.6 to 6.5)), and rofecoxib (1.9 (1.2 to 2.8)). Relative to rofecoxib, non-selective NSAID users were at significantly higher risk of upper gastrointestinal haemorrhage (1.9 (1.0 to 3.5)). Conclusions: This population based observational study found a lower short term risk of upper gastrointestinal haemorrhage for selective COX-2 inhibitors compared with non-selective NSAIDs.