The coronary risk of cyclooxygenase-2 (cox-2) inhibitors in subjects with a previous myocardial infarction

james brophy ^1*, Linda Levesques ¹ and Bin Zhang ¹

¹ McGill University, Canada

^* To whom correspondence should be addressed. E-mail: james.brophy{at}mcgill.ca.

Accepted 3 July 2006

Abstract

Background: Cyclooxygenase-2 (cox-2) selective inhibitors have been associated with cardiovascular side effects but previous studies have generally excluded individuals with a prior myocardial infarction (MI), thereby limiting our knowledge of their cardiotoxicity in this population.

Objectives: Our primary objective was to determine if a history of previous MI modified the risk of acute MI associated with the use of various nonsteroidal anti-inflammatory drugs (NSAIDs).

Methods: We identified a population-based cohort of 122,079 elderly individuals with and without previous MI and newly treated with an NSAID between January 01, 1999 and June 30, 2002 using the computerized health databases of Québec, Canada. We used a nested-case control approach for the analysis with controls matched on cohort entry and age. Current users of NSAIDs, those whose last prescription overlapped with the index date, were compared to individuals who were not exposed to NSAIDs in the year preceding the event. Rate ratios of acute MI were estimated using conditional logistic regression and adjusted for potential confounders.

Results: Rofecoxib users, both with and without a prior MI, were at increased risk of MI with a trend for greater risk among those with a previous event (RR, 1.59; 95% CI, 1.15-2.18 versus RR, 1.23; 95% CI, 1.05-1.45, p=0.14 for interaction). In contrast, celecoxib was only associated with an increased risk in individuals with a prior MI (RR, 1.40; 95% CI, 1.06-1.84 versus RR 1.03; 95% CI 0.88-1.20, p=0.04 for interaction). There was insufficient power to reliably assess risks among prior MI subjects treated with other NSAIDs, dose response relationships or interaction with aspirin.

Conclusions: Although only rofecoxib use was associated with an increased risk of MI in those without a previous event, both rofeocixb and celecoxib were associated with an excess risk of acute MI for current users with a prior history of MI. A large randomized trial is required to more completely and reliably assess the cardiovascular safety of celecoxib and traditional NSAIDs in this high risk patient population.

Keywords: adverse effects, cyclooxygenase inhibitors, myocardial infarction, nonsteroidal anti-inflammatory agents, pharmacoepidemiology

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