Long-Term Cardiovascular Risk of NSAID Use According to Time Passed After First-Time Myocardial Infarction: A Nationwide Cohort Study

Study Questions:

What is the cardiovascular risk associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the 5 years following first-time myocardial infarction (MI)?


This was a retrospective, nationwide, cohort study in which patients ages 30 years or older admitted with first-time MI between 1997 and 2009, and subsequent NSAID use, were identified through individual-level linkage of Danish registries of hospitalization and pharmacy prescription claims. Study outcomes were all-cause death and the combined endpoint of death caused by coronary artery disease or readmission for nonfatal MI associated with NSAID use in 1-year time intervals up to 5 years after inclusion.


Among 99,187 patients included, 43,608 (44%) were prescribed NSAIDs after the index MI. Through follow-up, 36,747 (37%) patients died and 28,696 (29%) experienced the combined endpoint of coronary death or nonfatal recurrent MI. Compared to noncurrent use of NSAIDs, there was a consistently increased risk of death among patients receiving any NSAID (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.49-1.69) after 1 year and HR, 1.63 (95% CI, 1.52-1.74) after 5 years, and coronary death or nonfatal recurrent MI (HR, 1.30; CI, 1.22-1.39) and HR, 1.41 (95% CI, 1.28-1.55). Naproxen was associated with the lowest relative cardiovascular risk; use of diclofenac was associated the highest risk.


In this Danish cohort, the use of NSAIDs was associated with persistently increased cardiovascular risk through the 5-year study period after first-time MI.


Over the past several years, there has been ongoing interest in the safety and potential cardiovascular risk of commonly used NSAIDs. These results add weight to existing recommendations that discourage the use of NSAIDs for patients with established cardiovascular disease. Alternatives to NSAID therapy and the heterogeneity of cardiovascular risk associated with different NSAID medications (e.g., the apparently lower risk profile of naproxen) should be considered, when clinically feasible.

Keywords: Cyclooxygenase 2 Inhibitors, Coronary Disease

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