Cyclooxygenase-2 Inhibitors and Heart Attacks: Varying Effects?

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The summary below is from the full report titled "Patients Exposed to Rofecoxib and Celecoxib Have Different Odds of Nonfatal Myocardial Infarction." It is in the 1 February 2005 issue of Annals of Internal Medicine (volume 142, pages 157-164). The authors are S.E. Kimmel, J.A. Berlin, M. Reilly, J. Jaskowiak, L. Kishel, J. Chittams, and B.L. Strom.

What is the problem and what is known about it so far?

People commonly use nonsteroidal anti-inflammatory drugs (NSAIDs) to relieve pain. Examples of older NSAIDs include aspirin, ibuprofen (Advil or Motrin), and naproxen (Aleve). Although these older NSAIDs are fairly safe, they can irritate the lining of the stomach and can cause ulcers and bleeding. Cyclooxygenase-2 (COX-2) inhibitors are a new type of selective NSAIDs. Examples of COX-2 inhibitors are celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra). They inhibitors do not injure the stomach lining as much as older NSAIDs do and cause fewer stomach problems and ulcers. However, they also cost more and require a doctor's prescription. Also, some COX-2 inhibitors increase the risk for heart disease. For example, rofecoxib was withdrawn from the market in September 2004 because a large trial found that it increased the risk for heart attacks and strokes. We do not know whether other COX-2 inhibitors have similar or different risks.

Why did the researchers do this particular study?

To see whether the risk for having a heart attack was similar among people taking rofecoxib; celecoxib; and older, nonselective NSAIDs.

Who was studied?

1718 patients with a first, nonfatal heart attack and 6800 adults with no history of a heart attack. All patients were 40 to 75 years of age from 5 counties in Pennsylvania.

How was the study done?

The researchers identified patients with recent heart attacks who were discharged from 36 hospitals between May 1998 and December 2002. They also identified adults with no history of a heart attack who were living in the same geographic region. They interviewed all participants by telephone and asked them several questions about past NSAID use. Patients with heart attacks reported use during the week before to their heart attack, while others reported use during the week before the interview. The researchers then compared NSAID use between patients with heart attacks and those with no history of a heart attack.

What did the researchers find?

Older NSAIDs were associated with a decreased risk for heart attack. Almost one third of the adults with no history of a heart attack reported taking older NSAIDs, while only about one fifth of those with a heart attack reported using these drugs. About 2.5% of the adults in both groups reported that they took 1 of 2 COX-2 inhibitors that were examined in the study. Use of rofecoxib was associated with a 2.72-higher odds of heart attack than was use of celecoxib. Rofecoxib was also associated with a higher odds of heart attack compared with older NSAIDs. Whether celecoxib was associated with a similar odds of heart attack compared with older NSAIDs was not clear.

What were the limitations of the study?

Only about 50% of eligible adults completed interviews. The study was not a randomized trial. Drug use was self-reported.

What are the implications of the study?

The risk for heart disease with rofecoxib and celecoxib may differ.