Treatment with nonsteroidal anti-inflammatory drug (NSAID) concomitant with antithrombotic therapy in patients who have experienced myocardial infarction (MI) may be associated with an increased risk for cardiovascular and bleeding events, according to study results published in Journal of the American College of Cardiology.

There are limited data available regarding the risk for cardiovascular events associated with the use of concomitant NSAIDs following MI, particularly in non-Western populations.

In this study, the primary outcome of interest was the frequency of thromboembolic cardiovascular events, a composite of recurrent MI, ischemic stroke or transient ischemic attack, or systemic arterial embolism. Clinically relevant bleeding events were analyzed as secondary outcomes.

A total of 108,232 patients with MI (72.1% men) from the Korean Health Insurance Review and Assessment Service were included in the analysis (mean follow-up, 2.3±1.8 years). A total of 1.8% and 1.9% of patients were prescribed ≥1 NSAID subtypes for ≥4 weeks in cardiovascular and bleeding events analyses, respectively. Among patients who received an NSAID prescription, diclofenac was the most frequently prescribed in analyses of both cardiovascular (71.8%) and bleeding events (68.9%).


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The composite cardiovascular events occurred in 24.2% of patients. The incidence of cardiovascular events was 118.8 per 100 person-years (95% CI, 105.9-131.6) and 10.5 per 100 person-years (95% CI, 10.4-10.6) in patients with and without concomitant NSAID use, respectively. Concomitant NSAID treatment significantly increased the risk for cardiovascular events compared with no NSAID treatment (hazard ratio [HR], 6.96; 95% CI, 6.24-7.77; P <.001).

The risk for cardiovascular events was highest among patients taking dexibuprofen (HR, 12.96; 95% CI, 7.37-22.79) and lowest for patients taking meloxicam (HR, 3.03; 95% CI, 1.68-5.47) and celecoxib (HR, 4.65; 95% CI, 3.17-6.82).

Bleeding events occurred in 23.4% of patients at an incidence of 55.5 per 100 person-years in patients taking concomitant NSAID treatment and 9.9 per 100 person-years in patients without concomitant NSAID treatment. Concomitant NSAID use significantly increased the risk for bleeding compared with nonuse (HR, 4.08; 95% CI, 3.51-4.73; P <.001).

The risk for bleeding events was comparable across all subgroups of NSAID treatment but was lowest in patients taking meloxicam (HR, 2.80; 95% CI, 1.40-5.60) and celecoxib (HR, 3.44; 95% CI, 2.20-5.39).

Study limitations include its lack of randomization which resulted in substantial differences in baseline characteristics between groups, and may limit the interpretation of results.

“The concomitant use of NSAIDs and post-MI antithrombotic medications was closely associated with increased risk for cardiovascular and bleeding events,” the study authors concluded. “Although NSAID treatment should be limited after MI, selective and relative [cyclooxygenase]-2 inhibitors could be considered a primary choice on the basis of their observed relative safety profile in patients with MI when NSAID use is unavoidable.”

Reference

Kang DO, An H, Park GU, et al. Cardiovascular and bleeding risks associated with nonsteroidal anti-inflammatory drugs after myocardial infarction. JACC. 2020;76(5):518-529. doi:10.1016/j.jacc.2020.06.017