Linda E. Lévesque, BScPhm, MSc; James M. Brophy, MD, PhD; Bin Zhang, MSc
Disclaimer: This study is based on nonidentifiable data provided by several Québec Government agencies. The interpretation and conclusions contained herein do not necessarily represent those of the government of Québec or these agencies.
Grant Support: By a grant from the Canadian Institutes of Health Research (CIHR grant MOP62871). Dr. Brophy is a Physician-Scientist of the Fonds de la recherche en santé du Québec.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: James Brophy, MD, PhD, Cardiology Division, Room M4.76, McGill University Health Centre, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Ms. Lévesque and Drs. Brophy and Zhang: McGill University Health Centre, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada.
Author Contributions: Conception and design: L.E. Lévesque, J.M. Brophy.
Analysis and interpretation of the data: L.E. Lévesque, J.M. Brophy, B. Zhang.
Drafting of the article: L.E. Lévesque, J.M. Brophy.
Critical revision of the article for important intellectual content: L.E. Lévesque, J.M. Brophy.
Final approval of the article: L.E. Lévesque, J.M. Brophy.
Provision of study materials: J.M. Brophy.
Statistical expertise: L.E. Lévesque, J.M. Brophy, B. Zhang.
Obtaining of funding: J.M. Brophy.
Administrative, technical, or logistic support: L.E. Lévesque, J.M. Brophy.
Collection and assembly of data: L.E. Lévesque, J.M. Brophy.
Cyclooxygenase-2 (COX-2) selective inhibitors have been marketed since 1999 as safer alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs). Debate about their cardiac safety has culminated in the recent withdrawal of rofecoxib. Additional studies are needed to better understand this risk and to determine whether this safety concern represents a class effect.
To assess the influence of various NSAIDs on the risk for a first myocardial infarction (MI).
Population-based, retrospective cohort study analyzed using a time-matched, nested case–control approach.
113 927 elderly persons without previous MI and newly treated with an NSAID between 1 January 1999 and 30 June 2002.
NSAID exposure and occurrence of MI assessed by using Québec's administrative health databases.
Compared with no use of NSAIDs in the year preceding the event, current use of rofecoxib was associated with an increased risk for an acute MI (rate ratio [RR], 1.24 [95% CI, 1.05 to 1.46]) that was more pronounced at higher doses (RR, 1.73 [CI, 1.09 to 2.76]). The concomitant use of aspirin appears to decrease the risk associated with low-dose rofecoxib (RR, 1.00 [CI, 0.77 to 1.28]) but not with high-dose rofecoxib (RR, 2.36 [CI, 1.27 to 4.39]). No increased risks were observed with celecoxib (RR, 0.99 [CI, 0.85 to 1.16]) or the other NSAIDs.
The study could not completely account for all potential confounders, including over-the-counter use of aspirin and ibuprofen.
These results provide evidence of an increased risk for acute MI in current users of rofecoxib among elderly persons with no history of MI. This risk appears greater at higher doses. Aspirin use mitigates the risk associated with low-dose but not high-dose rofecoxib. There was no evidence of an increased risk with the other NSAIDs.
Do risks for myocardial infarction (MI) differ among cyclooxygenase-2 (COX-2) selective inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs)?
This retrospective study involving 113 927 people older than age 65 years used Québec's administrative health databases to examine associations between various NSAIDs and risk for a first MI. Compared with nonuse of NSAIDs, use of rofecoxib was associated with a 1.24 higher relative risk for MI (95% CI, 1.05 to 1.46), while neither celecoxib nor other NSAIDs were associated with statistically significant increased risks.
Although analyses controlled for potential confounders, unmeasured factors such as over-the-counter use of aspirin and ibuprofen could have affected results.
Flow of study cohort.
Table 1. Characteristics of Case-Patients and Controls
Table 2. Crude and Adjusted Rate Ratios of Acute Myocardial Infarction for Use of Various Anti-Inflammatory Agents
Table 3. Crude and Adjusted Rate Ratios of Acute Myocardial Infarction for Current Use of Celecoxib and Rofecoxib according to Dose
Table 4. Crude and Adjusted Rate Ratios of Acute Myocardial Infarction for Current Use of Anti-Inflammatory Agents according to Concomitant Use of Aspirin and Dose of Cyclooxygenase-2 Selective Inhibitors
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Lévesque LE, Brophy JM, Zhang B. The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors: A Population Study of Elderly Adults. Ann Intern Med. ;142:481–489. doi: 10.7326/0003-4819-142-7-200504050-00113
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Published: Ann Intern Med. 2005;142(7):481-489.
Acute Coronary Syndromes, Cardiology, Coronary Heart Disease, Emergency Medicine, Geriatric Medicine.
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