• In this meta-analysis of individual patient data, investigators examined records from Canadian and European healthcare databases to determine if exposure to an oral non-steroidal anti-inflammatory drug (NSAID) was associated with an increased risk of acute myocardial infarction (MI). Data from 446,763 individuals were included; 61,460 of these individuals experienced an acute MI. Investigators determined that any dose of NSAID for any length of time (1 week, 1 month, or over 1 month) significantly increased risk of acute MI. This finding was consistent with all the NSAIDs studied (celecoxib, ibuprofen, diclofenac, naproxen, and rofecoxib). Higher doses of NSAIDs were associated with greater risk, but extended duration of NSAID use did not confer any additional risk over short-term use.
• This meta-analysis found that all NSAIDs increase the risk for acute MI, even with short-term use.

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.

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Journal Abstract