The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada

• Published in: Pharmacoepidemiology and drug safety Vol. 18; no. 11; pp. 1016 - 1025
• Main Authors: Varas-Lorenzo, Cristina, Castellsague, Jordi, Stang, Mary Rose, Perez-Gutthann, Susana, Aguado, Jaume, Rodriguez, Luis Alberto García
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-11-2009
• Subjects: Adult; Aged; Aged, 80 and over; Antiinflammatory agents; Case-Control Studies; Cohort Studies; cohort study; coxibs; Cyclooxygenase 2 Inhibitors - adverse effects; Dose-Response Relationship, Drug; Drugs; Hospitalization; Hospitals; Humans; Male; Middle Aged; Mortality; Myocardial infarction; Myocardial Infarction - chemically induced; Myocardial Infarction - complications; Myocardial Infarction - epidemiology; NSAIDs; Risk Factors; Saskatchewan - epidemiology; Time Factors; Saskatchewan; Canada, Saskatchewan
• ISSN: 1053-8569; 1099-1557; 1099-1557
• DOI: 10.1002/pds.1815

Background
Meta‐analyses of observational studies show variability in the risk of acute myocardial infarction (AMI) among non‐steroidal anti‐inflammatory drugs (NSAIDs), with an increase in risk for rofecoxib and diclofenac, and no increase in risk for celecoxib, naproxen, or ibuprofen.
Methods and Results
We identified a cohort of 364 658 individuals aged 40–84 years who were enrolled in Saskatchewan Health, Canada, from 15 November 1999 to 31 December 2001. A nested case–control analysis compared 3252 incident cases of hospitalized AMI and out‐of‐hospital CHD deaths with 20 002 controls randomly sampled from the cohort. The incidence of AMI/CHD was 5.1 per 1000 person‐years (95%CI: 5.0–5.3). The adjusted ORs (95%CI) of AMI/CHD in current users of individual NSAIDs compared with non‐use were: celecoxib (1.11; 0.84–1.47), rofecoxib (1.32; 0.91–1.91), diclofenac (1.02; 0.75–1.38), naproxen (1.57; 0.98–2.52), ibuprofen (1.59; 0.88–2.89), and indomethacin (1.34; 0.81–2.19). Long‐term use of rofecoxib was compatible with an increased risk (OR = 1.46; 0.97–2.22) while estimates of other individual NSAIDs were close to unity. Overall NSAID use was associated with a 30% increased risk of nonfatal AMI but was absent for fatal AMI/CHD.
Conclusions
This study showed a modest increased risk of AMI/CHD with various traditional NSAIDs and COX‐2 inhibitors. Confidence intervals of estimated ORs included the null value for most comparisons. The study confirmed that the differentiation between traditional NSAIDs and COX‐2 inhibitors is not a reliable tool for predicting cardiovascular risk associated with NSAIDs. Copyright © 2009 John Wiley & Sons, Ltd.