Using a nonsteroidal anti-inflammatory drug after myocardial infarction increased the relative risk for death or second MI by as much as 45%, findings from a recent study involving more than 83,000 patients reveal.

“These results challenge the view that NSAIDs are not harmful during short-term treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established [CVD] is required,” Anne-Marie Schjerning Olsen, MB, of Copenhagen University Hospital in Gentofte, Denmark, and colleagues wrote in Circulation.

Particularly concerning was the high risk for death associated with the NSAID diclofenac (Voltaren, Cataflam) after just one week of use (HR=3.52) — an even higher risk than was associated with the selective COX-2 inhibitor, rofecoxib (Vioxx), which was withdrawn from the market in 2004.

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To perform the analyses, the researchers used detailed records of patient admissions, readmissions and medication use in Denmark, as well is data from the central death registry to determine the time to adverse event among patients with prior MI who took NSAIDs.

They identified 83,675 patients that were admitted for treatment of first MI from 1997 to 2006 and found that 42.3% had received an NSAID during follow-up. A total of 35,257 deaths or recurrent MIs occurred. Mean patient age was 68 years and more than half of patients were men (63%).

“In brief, overall NSAID treatment was associated with a statistically significantly increased risk of death at the beginning of the treatment, and the risk persisted throughout the course of treatment,” the researchers wrote.

The researchers also analyzed risk by drug and found the following:

  • Increased risk of death with the other selective COX-2 inhibitor, celecoxib (Celebrex) occurred when treatment lasted two weeks to a month, vs. the one to two weeks previously identified for patients taking rofecoxib.
  • Ibuprofen had the lowest initial risk, just a 4% increase for treatments lasting seven days or less (HR 1.04, 95% CI 0.83 to 1.30).
  • Naproxen increased the risk for death or recurrent MI by 76% after one week (HR 1.76, 95% CI 1.04 to 2.98), but the risk went down over the duration of treatment. Among patients whose treatments lasted 30 to 90 days, the increased risk was 15% (HR 1.15, 95% CI 0.80 to 1.65).

The study had several limitations, including its observational design; inability to distinguish why patients initiated NSAID use in the first place (certain medical conditions could predispose patients to CV risks); and information bias (patients may not take medication as directed and exposure to medication may run longer than a prescription indicates).

Although more randomized control clinical trials are needed to confirm the results,  in the meantime clinicians should “limit NSAID use to the absolute minimum in patients with established [CVD],” the researchers wrote.

Schjerning Olsen AM. Circulation. 2011; DOI: 10.1161/CIRCULATIONAHA.110.004671.