Background: Cyclo-oxygenase-2 selective inhibitors have been associated with cardiovascular side effects, but previous studies have generally excluded people with previous myocardial infarction, thereby limiting our knowledge of their cardiotoxicity in this population.
Objectives: To determine whether a history of myocardial infarction modified the risk of acute myocardial infarction associated with the use of various non-steroidal anti-inflammatory drugs (NSAIDs).
Methods: A population-based cohort of 122 079 elderly people with and without previous myocardial infarction newly treated with an NSAID between 1 January 1999 and 30 June 2002 were identified using the computerised health databases of Québec, Canada. A nested-case–control approach was used for the analysis, with controls matched by cohort entry and age. Current users of NSAIDs, those whose last prescription overlapped with the index date, were compared with those who were not exposed to NSAIDs in the year preceding the event. Rate ratios of acute myocardial infarction were estimated using conditional logistic regression and adjusted for potential confounders.
Results: Users of rofecoxib, both with and without previous myocardial infarction, were at increased risk of myocardial infarction, with a trend for greater risk among those with a previous event (rate ratio (RR) 1.59, 95% confidence interval (CI) 1.15 to 2.18 v RR 1.23, 95% CI 1.05 to 1.45; p = 0.14 for interaction). By contrast, celecoxib was only associated with an increased risk in people with previous myocardial infarction (RR 1.40, 95% CI 1.06 to 1.84 v RR 1.03, 95% CI 0.88 to 1.20; p = 0.04 for interaction). The available power was insufficient to reliably assess risks among patients with previous myocardial infarction treated with other NSAIDs, dose–response relationships or interaction with aspirin.
Conclusions: Although only rofecoxib use was associated with an increased risk of myocardial infarction in those without a previous event, both rofecoxib and celecoxib were associated with an excess risk of acute myocardial infarction for current users with a history of myocardial infarction. A large randomised trial is required to more completely and reliably assess the cardiovascular safety of celecoxib and traditional NSAIDs in this population of high-risk patients.
- Cox-2, cyclo-oxygenase-2
- NSAID, non-steroidal anti-inflammatory drug
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↵* Also Department of Medicine, McGill University Health Centre, McGill University, Montréal, Canada
↵† Also Department of Community Health and Epidemiology, Queen’s University, Kingston, Canada
Funding: This study was funded by a grant from the Canadian Institutes of Health Research (CIHR grant MOP62871), who had no role in the design, conduct, interpretation or reporting of the study or the decision to submit the manuscript for publication.
Competing interests: None.
JMB is a Physician–Scientist of the Fonds de la Recherche en Santé du Québec. This study is based on non-identifiable data provided by several agencies of the Québec government. The interpretation and conclusions contained herein do not necessarily represent those of the government of Québec or these agencies.