Even Short-Term NSAID Use Risky in Cardiac Patients

Megan Brooks

May 09, 2011

May 9, 2011 — In patients with prior myocardial infarction (MI), most nonsteroidal anti-inflammatory drugs (NSAIDs), even when taken for as little as 1 week, are associated with an increased risk for death and recurrent MI, new observational data indicate.

Use of NSAIDs was associated with a 45% increased risk for death or recurrent MI in the first 7 days of treatment and a 55% increased risk if treatment continued to 3 months. The findings were published online May 9 in Circulation.

"We found that short-term treatment with most NSAIDs was associated with increased and instantaneous cardiovascular risk," first author Anne-Marie Schjerning Olsen, MB, from Copenhagen University in Hellerup, Denmark, told Medscape Medical News.

Dr. Anne-Marie Schjerning Olsen

"Our results indicate that there is no apparent safe therapeutic window for NSAIDs in patients with prior MI and challenge the current recommendations of low-dose and short-term use of NSAIDs as being safe," she said.

Results 'Completely Consistent' With 2007 AHA Advisory

In a 2007 scientific statement, the American Heart Association (AHA) advised clinicians about the risks of NSAID use among patients with known cardiovascular disease or those at risk for ischemic heart disease and provided a stepped-care approach for use of these agents in this patient population.

Asked to comment on the new study, Elliott Antman, MD, from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, and lead author of the 2007 advisory, said, "Essentially, what this paper shows is that there is a gradient of risk among NSAIDs; some are associated with more risk than others; none appear to be completely safe, and the researchers could not identify a period that appeared to be safe, no matter how short."

"This is completely consistent with the advice that we put forward in 2007, which is to use the safest drug, in the lowest dose required to control musculoskeletal symptoms, for the shortest period of time," Dr. Antman told Medscape Medical News.

"We do have to be practical here," Dr. Antman said, "because despite very best efforts with physical therapy and nonpharmacologic treatments, there are individuals who have severe, debilitating arthritis, lupus, or rheumatoid arthritis and we do have to have a treatment plan for those patients." The AHA's stepped-care approach provides such a plan, Dr. Antman noted.

First Time-to-Event Analysis

Using the Danish National Patient Registry, Dr. Olsen and colleagues identified 83,675 patients who were admitted to a hospital with a first MI between 1997 and 2006 and were discharged alive. Their average age was 68 years, and 63% were men.

At least 1 prescription claim for NSAID treatment after discharge was identified for 35,405 patients (42.3%), most commonly ibuprofen (23%) and diclofenac (13.4%). The most commonly prescribed selective cyclooxygenase (COX)-2 inhibitors were rofecoxib (4.7%) and celecoxib (4.8%).

During the observation period, 35,257 deaths or recurrent MIs (42.1%) were registered in the database. According to the investigators, the risk for death or recurrent MI was elevated at the beginning of NSAID treatment (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.29 - 1.62) and the risk persisted throughout treatment (HR after 90 days, 1.55; 95% CI, 1.46 - 1.64).

Particularly worrying was the fact that…diclofenac was associated with early and higher cardiovascular risk than…rofecoxib, which was withdrawn from the market in 2004 due to its unfavorable cardiovascular risk profile.

All NSAIDs, except naproxen, were associated with an increased risk for death or recurrent MI, with diclofenac having the highest risk (HR in the first week of treatment, 3.26; 95% CI, 2.57 - 3.86).

"Particularly worrying," Dr. Olsen told Medscape Medical News, "was the fact that the widely used nonselective NSAID diclofenac was associated with early and higher cardiovascular risk than the selective COX-2 inhibitor rofecoxib, which was withdrawn from the market in 2004 due to its unfavorable cardiovascular risk profile."

"The accumulating evidence suggests that we must limit NSAID use to the absolute minimum in patients with established cardiovascular disease," she added.

"If NSAID therapy is necessary for patients with known cardiovascular disease, the doctors should choose a more selective COX-1 inhibitor in minimum dose (eg, naproxen ≤ 500 mg daily or ibuprofen ≤ 1200 mg daily) for the shortest period of time," she added.

Dr. Antman said this paper provides a "good reminder" for clinicians and patients about the risks of NSAIDs in this patient population.

"Many of the drugs that we are talking about," he noted, "can be obtained over-the-counter, and it is the presumption of many patients that if it is a drug that they can get over-the-counter it must be 'safer.' Very often they don't report those medications to their physician when they go for an office visit."

The authors and Dr. Antman have reported no relevant financial relationships.

Circulation. Published online May 9, 2011. Abstract


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