NSAIDs associated with increased risk of bleeding, cardiovascular events after MI

Compared to other NSAIDs, celecoxib and meloxicam were associated with a lower risk of bleeding or cardiovascular events among Korean patients who had a myocardial infarction (MI).

The use of NSAIDs after a myocardial infarction (MI) was associated with a significantly increased risk for cardiovascular and bleeding events compared to no NSAID treatment, a Korean study found.

Researchers used two nationwide organizations that validate health care services and medical costs in South Korea to access detailed medical information on 98% of the Korean population. The study enrolled 108,232 patients admitted for a first MI between 2009 and 2013, with a follow-up period of 2.3 years. Researchers tracked prescriptions for antithrombotic medications, including aspirin, clopidogrel, and oral vitamin K antagonists, as well as NSAIDs, including naproxen, ibuprofen, diclofenac, celecoxib, and meloxicam. Results were published by the Journal of the American College of Cardiology on July 27.

During the overall follow-up period, slightly less than 2% of the patients were prescribed one or more NSAID subtypes for at least four consecutive weeks, with diclofenac being the most frequently prescribed (more than a third of NSAID prescriptions). NSAID treatment was associated with an increased risk for cardiovascular events (hazard ratio [HR], 6.96; 95% CI, 6.24 to 6.77; P<0.001) and bleeding events (HR, 4.08; 95% CI, 3.51 to 4.73; P<0.001) compared with no NSAID treatment. Among NSAID subtypes, the risk for cardiovascular and bleeding events was lowest with the use of celecoxib (HRs, 4.65 [95% CI, 3.17 to 6.82; P<0.001] and 3.44 [95% CI, 2.20 to 5.39; P<0.001], respectively) and meloxicam (HRs, 3.03 [95% CI, 1.68 to 5.47; P<0.001] and 2.80 [95% CI, 1.40 to 5.60; P<0.001], respectively).

The study authors concluded that clinicians should limit prescribing of NSAIDs as much as possible after an MI; however, the data suggest that they could consider celecoxib and meloxicam when NSAIDs must be prescribed. The study had several limitations, including a lack of available data on over-the-counter NSAID use and mortality. Noting that these findings had been shown before only in Western populations, the researchers recommended further studies in neighboring countries, such as Japan and Taiwan, to examine the results in similar ethnic populations.

The authors wrote, “From the perspective of pharmacodynamics, celecoxib and meloxicam are currently available NSAIDs that exhibit high selectivity for COX-2 over COX-1 inhibition. Different selectivity of individual NSAIDs for COX isoenzymes could be suggested as a possible underlying mechanism that contributes to the relative safety features of selective and relative COX-2 inhibitors, including celecoxib and meloxicam.”

The finding of fewer adverse events with celecoxib and meloxicam suggests that these drugs “may deserve a more central place in the anti-inflammatory armamentarium,” according to an accompanying editorial. “Ultimately, this important study confirms that NSAID use post-MI significantly increased cardiovascular and bleeding risks, expands this fact to the Asian population, and provides information guiding treatment decisions.”