Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDS) and antithrombotic medications post myocardial infarction (MI) was closely associated with an increased risk of cardiovascular and bleeding events in Korean patients, according to a nationwide study in Korea published July 27 in the Journal of the American College of Cardiology. According to the authors, this is the largest contemporary cohort of patients with MI to examine the concomitant use of NSAIDs, and the first study of its kind to confirm these data in a non-Western patient population.

Using the National Health Insurance Service (NHIS) and the Korean Health Insurance Review and Assessment Service (HIRA), researchers accessed detailed medical information of 98% of the Korean population, including patient diagnosis, treatment and prescriptions. The analysis included 108,232 patients admitted for a first MI between 2009 and 2013, with a follow-up period of 2.3 years. The average age was 64.2 years, and 72.1% were men.

Researchers tracked prescriptions for antithrombotic medications (including aspirin, clopidogrel and oral vitamin K antagonist) and NSAIDs (including naproxen, ibuprofen, diclofenac, celecoxib, meloxicam and more). Among antithrombotic medications, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was the most frequently prescribed at 87.9%. Diclofenac was the most frequently prescribed NSAID in patients with either cardiovascular or bleeding event outcomes, 71.8% and 68.9%, respectively. The primary and secondary outcomes were thromboembolic cardiovascular and clinically relevant bleeding events. Ongoing NSAID treatment and subtypes of NSAIDs were assessed for the risk for adverse clinical events.

Cardiovascular and bleeding risk increased within seven days after patients began NSAID treatment. Compared with no NSAID treatment, concomitant NSAID treatment significantly increased the risk for cardiovascular events (hazard ratio [HR], 6.96; 95% confidence interval [CI], 6.24-6.77; p<0.001) and bleeding events (HR, 4.08; 95% CI, 3.51-4.73; p<0.001). A primary cardiovascular event developed in 26.2% of patients prescribed NSAIDs.

Among the NSAID subtypes, the lowest risk for cardiovascular and bleeding events was with celecoxib (HR, 4.65; 95% CI, 3.17-6.82; p<0.001, and 3.44; 95% CI, 2.20-5.39; p<0.001, respectively) and meloxicam (HR, 3.03; 95% CI, 1.68-5.47; p<0.001, and 2.80; 95% CI, 1.40-5.60; p<0.001, respectively). Concomitant NSAIDs also significantly increased the risk for cardiovascular events in the dual antiplatelet therapy group (HR, 6.93; 95% CI, 6.15-7.80; p<0.001) and the single antiplatelet therapy group (HR, 7.05; 95% CI, 4.03-12.33; p<0.001) subgroups. Secondary bleeding events developed in 23.4% of patients.

Study author Dong Oh Kang, MD, et al, explained, "Our study adds important value to the currently available evidence for concomitant NSAID treatment after MI by constituting global evidence that encompasses diverse population groups. The main advantage of the present study was its use of a nationwide prescription claims database that reflects real-world clinical practice treatment trends."

In an accompanying editorial comment, Juan J. Badimon, PhD, FACC, and Carlos G. Santos-Gallego, MD, AACC, note, "There is no free lunch in medicine, so if NSAID therapy in patients post-MI is inevitable, we have to understand which price we are paying for pain relief." They conclude, "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."

Clinical Topics: Cardiovascular Care Team

Keywords: Anti-Inflammatory Agents, Anti-Inflammatory Agents, Non-Steroidal, Naproxen, Diclofenac, Ibuprofen, Platelet Aggregation Inhibitors, Aspirin, Fibrinolytic Agents, Confidence Intervals, Myocardial Infarction, ACC International

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