Abstract
The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22–1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88–1.11). In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen, supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so further investigation into the risk of AMI is warranted because the potential for harm can be substantial.
Highlights
One of the most revelatory issues concerning pharmaceuticals in recent years has been the relationship found between selective cyclo-oxygenase (COX)-2 inhibitors and cardiovascular thrombotic adverse events such as acute myocardial infarction (AMI) [1,2,3,4,5]
A further two studies were identified by hand searching [15,16], of which one was excluded because it compared the effects of one nonsteroidal antiinflammatory drugs (NSAIDs) with current use of three other NSAIDs but it did not have a control population of remote users or non-users [15]
Contrary to the majority of the studies included in the review, two studies were conducted in selected populations; one study [17] included only postmenopausal women and the other [16] was limited to patients with rheumatoid arthritis
Summary
One of the most revelatory issues concerning pharmaceuticals in recent years has been the relationship found between selective cyclo-oxygenase (COX)-2 inhibitors and cardiovascular thrombotic adverse events such as acute myocardial infarction (AMI) [1,2,3,4,5]. New evidence suggests that there be an association between these nonselective NSAIDs and cardiovascular adverse effects, and that the risk may be similar with this class of drugs to that with COX-2 selective NSAIDs [6]. NSAIDs are among the most popular of prescribed drugs and have proven effectiveness in relieving symptoms of inflammation, including pain; they may have a role in cancer prevention [7]. Both their benefits and adverse effects are due to the inhibition of either COX-1 or COX-2 enzymes. Recent studies have shown an unequivocal increase in risk of cardiovascular thrombotic events in patients treated with these drugs [15]
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