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BMJ. 2017 May 9;357:j1909. doi: 10.1136/bmj.j1909.

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data.

Author information

1
Department of Pharmacy and Research Centre, Centre hospitalier de l'Université de Montréal, Montreal, H2X 1N4, Canada michele.bally.chum@ssss.gouv.qc.ca.
2
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.
3
Technology Assessment Unit of the McGill University Health Centre, Montreal, Canada.
4
Division of Clinical Epidemiology, McGill University Health Centre-Research Institute, Montreal, Canada.
5
Unit of Primary Care, Hospital District of Helsinki and Uusimaa, Helsinki, Finland.
6
Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany.
7
Department of Medicine, McGill University, Montreal, Canada.

Abstract

Objective To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs).Design Systematic review followed by a one stage bayesian individual patient data meta-analysis.Data sources Studies from Canadian and European healthcare databases.Review methods Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. Exposure and outcomes Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction.Results A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations.Conclusions All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.

PMID:
28487435
PMCID:
PMC5423546
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: MB reports grants from McGill University Health Centre Research Institute during the conduct of the study and personal fees from Institut national d’excellence en santé et services sociaux, outside the submitted work; JMB reports serving on the Data Monitoring Committee for the PRECISION trial, which is sponsored by Pfizer, during the conduct of the study; BR reports personal fees from Certara, outside the submitted work; EG reports personal fees from Astellas, grants and personal fees from Bayer, GSK, Novartis, Takeda, and Nycomed, and grants from STADA, Sanofi-Aventis, and Celgene, outside the submitted work.

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