Short-term NSAIDs associated with increased myocardial infarction risk after previous heart attacks

Even short-term treatment with most nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased risk of death and a subsequent myocardial infarction (MI) in patients with prior heart attacks, reports a national cohort population study from Denmark.

Because patients may unavoidably receive NSAID treatment for a short period of time despite existing precautions in those with established cardiovascular disease, researchers studied the duration of NSAID treatment and cardiovascular risk. Patients 30 years of age or older admitted for a first MI from 1997 to 2006 and their subsequent NSAID use were identified using ICD codes and pharmacy records. Results appeared online May 9 in Circulation.

Of the 83,677 patients discharged alive after their first heart attack, 42.3% received NSAIDs during follow-up. There were 35,257 deaths or recurrent MIs.

NSAIDs were significantly associated with an increased risk of death/recurrent MI (hazard ratio [HR], 1.45) at the beginning of the treatment, and the risk persisted throughout the treatment course (HR, 1.55). Diclofenac was associated with the highest risk (HR, 3.26 for death/MI at day 1 to 7 of treatment). Rofecoxib was associated with increased risk of death after treatment from 7 to 14 days, while celecoxib was associated with increased risk of death after 14 to 30 days. Ibuprofen showed an increased risk when used for more than one week. Naproxen was not associated with an increased risk of death or MI for the entire treatment duration.

“It is noteworthy that a commonly used nonselective NSAID like diclofenac is associated with an even higher risk of death at the beginning of the course of treatment than the selective COX-2 inhibitor rofecoxib, which was withdrawn from the market in 2004,” the authors wrote. But they later added that while naproxen had the lowest cardiovascular risk, it is associated with more gastrointestinal bleeding events.

“Our data challenge the current recommendations by the American Heart Association regarding NSAID treatment in patients with established cardiovascular disease,” the authors concluded, “because we demonstrate that even short-term NSAID treatment is associated with increased cardiovascular risk in patients with prior MI; i.e., there essentially appears to be no safe therapeutic window for NSAID treatment. Therefore, the current approach of recommending short-duration treatment in patients with established cardiovascular disease who require NSAIDs may need revision.”