According to a review published in The BMJ, all oral non-steroidal anti-inflammatory drugs (NSAIDs) were found to be associated with an increased risk of acute myocardial infarction, with the onset of risk occurring within the first week of use.

In order to determine the factors, time course, and risks of acute myocardial infarction associated with oral NSAIDs, researchers from McGill University, Montreal, Canada performed a systematic review and a one stage bayesian individual patient data meta-analysis. They searched for studies from Canadian and European healthcare databases that were conducted in both the general population and in elderly patients where acute myocardial infarction was documented as a specific outcome. The studies included in the analysis compared the risk of acute myocardial infarction in NSAID users vs. non-users as well as the risks associated with selective cyclooxygenase-2 (COX-2) inhibitors (including rofecoxib) vs. traditional NSAIDs. Drug dose, duration of use, and recency of use were also evaluated.

“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,” said the authors. 

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The researchers identified 446,763 patients, including 61,460 individuals with acute myocardial infarction. The analysis showed that any NSAID dose taken for 1 week, 1 month, or >1 month was associated with a higher risk of myocardial infarction. The probability of increased risk for acute myocardial infarction (posterior probability of odds ratio [OR] >1.0) with NSAID use for 1–7 days was 99% for diclofenac, naproxen, and rofecoxib, 97% for ibuprofen, and 92% for celecoxib. Greatest harm was noted with short-term NSAID use (8–30 days) at high daily doses (celecoxib >200mg, diclofenac >100mg, ibuprofen >1200mg, and naproxen >750mg).

The corresponding ORs were highest with rofecoxib at 1.58 (95% CI: 1.07–2.17), followed by 1.53 (95% CI: 1.07–2.33) for naproxen, 1.50 (95% CI: 1.06–2.04) for diclofenac, 1.48 (95% CI: 1.00–2.26) for ibuprofen, and 1.24 (95% CI: 0.91–1.82) for celecoxib. In addition, higher NSAID doses were associated with greater risk.

Lead author and epidemiologist, Michele Bally, added, “With use for longer than one month, risks did not appear to exceed those associated with shorter durations.” The risk associated with celecoxib use was similar to that of traditional NSAIDs but lower than for rofecoxib. Overall, the risk for acute myocardial infarction was highest during the first month of use and with higher doses.

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