NSAIDS MAY HIKE LONG-TERM CV RISK POST MI

Action Points

• The cardiovascular risk after the first myocardial infarction typically declines rapidly during the first year.
• Note however that this study shows that the use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) may confer a long-term risk of adverse cardiovascular events, a Danish population study found.

Of the nearly 100,000 patients with first-time myocardial infarction (MI) included in the analysis, those taking NSAIDs had a "persistent" increased risk of all-cause death at 1 year (HR 1.59, 95% CI 1.49 to 1.69) and at 5 years (HR 1.63, 95% CI 1.52 to 1.74), according to Anne-Marie Olsen, MD, a research fellow at Copenhagen University Hospital Gentofte in Hellerup, Denmark, and colleagues.

In addition, those taking these anti-inflammatory drugs had a 41% increased risk of a second MI and a 30% increased risk of coronary death during the 5-year follow-up, they reported online in Circulation: Journal of the American Heart Association.  While epidemiological studies such as this cannot establish causality, they said their results are further evidence of an association between COX-2 inhibitors and severe adverse cardiovascular events.

"We advise long-term caution in using NSAIDs for patients after MI," they concluded. They also suggested that the availability of over-the-counter nonselective NSAIDS such as diclofenac and ibuprofen "should be reconsidered."

Although taking any NSAID increased the risk compared with taking none, use of diclofenac was associated with the highest risk, they pointed out.  Other NSAIDs evaluated in this study were rofecoxib (Vioxx), celecoxib (Celebrex), naproxen (Aleve, among other brand names), and others.  At the time of the study, only ibuprofen (200 mg) was available over the counter in Denmark.

Despite a focused update in 2007 from the American Heart Association cautioning against the use of NSAIDs for those with cardiovascular disease, many still receive these drugs, although for shorter periods (Circulation 2007; 115: 1634-1642), Olsen and colleagues wrote.

Because the long-term effects of NSAIDs among those with a first MI were unclear, researchers analyzed data from 99,187 patients in the Danish National Patient Registry from 1997 to 2009.

There were more men (64%) than women in the study, the mean age was 69, and 44% had filled at least one prescription of NSAIDs.  Researchers found that the overall adverse risks associated with NSAIDs "remained virtually unchanged throughout all 5 years after discharge from hospital after the first MI."

This is in contrast to the typical risk of cardiovascular mortality and morbidity following an MI, which declines as time passes, Olsen and colleagues noted. However, rofecoxib and diclofenac conferred a greater risk of death and the composite of recurrent MI and coronary death over time compared with other NSAIDs, especially naproxen, which had the lowest risk.

Although it might be preferable to prescribe naproxen, researchers noted that the drug was associated with a higher risk of gastrointestinal bleeding than rofecoxib.  They also found that those not taking anti-inflammatory drugs had a decreased risk of adverse events over the 5 years following the index MI.

The study has several limitations, the authors noted, including its observational nature, some missing clinical data, no data on the use of over-the-counter aspirin, and no way to determine if patients adhered to their prescription.  However, a strength of the study is that these data are from one country and are known to be accurate, they said.

They concluded that their findings support previous results that suggest there is "no apparent safe treatment window" for NSAIDs among patients with MI.

POSTED BY:  Steven Almany M.D.