Risk for Heart Attacks with Different NSAIDs

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The summary below is from the full report titled "The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors: A Population Study of Elderly Adults." It is in the 5 April 2005 issue of Annals of Internal Medicine (volume 142, pages 481-489). The authors are L.E. Lévesque, J.M. Brophy, and B. Zhang.

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 NSAIDs include aspirin, etodolac (Lodine), ibuprofen (Advil or Motrin), and naproxen (Aleve). NSAIDs can irritate the lining of the stomach and cause ulcers and bleeding. Drugs called cyclooxygenase-2 (COX-2) inhibitors are a particular "selective" type of NSAID that may not injure the stomach lining as much as other NSAIDs. Examples of COX-2 inhibitors are celecoxib (Celebrex), meloxicam (Mobicox), rofecoxib (Vioxx), and valdecoxib (Bextra). Some COX-2 inhibitors may 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 For example, rofecoxib was withdrawn from the market in September 2004 because a large trial found that it increased the risk for heart attacks and strokes.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 and nonselective NSAIDs 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 older adults taking selective and nonselective NSAIDs.

Who was studied?

113,927 adults older than 65 years of age in Québec, Canada.

How was the study done?

The researchers used administrative databases to identify older adults who were and were not receiving NSAIDs and who were and were not hospitalized for a first heart attack. They then compared the risk for having a heart attack between adults who had not received NSAIDs in the past year and those who were currently receiving NSAIDs. They examined 5 groups of NSAIDs: 3 selective COX-2 inhibitors (rofecoxib, celecoxib, meloxicam), 1 partially selective NSAID (naproxen), and traditional nonselective NSAIDs. They considered rofecoxib dosages greater than 25 mg daily to be high dose. They also examined whether concomitant aspirin use affected risks for heart attack among rofecoxib users.

What did the researchers find?

People prescribed rofecoxib had a 1.24 higher relative risk for heart attack compared to those prescribed no NSAIDs. Higher doses of rofecoxib were associated with higher risks. Concomitant aspirin use lessened the risks associated with low-dose, but not high-dose, rofecoxib. Celecoxib, meloxicam, and the other NSAIDs were not associated with increased risk for heart attack.

What were the limitations of the study?

The researchers did not assess over-the-counter use of aspirin and ibuprofen and whether people took prescribed amounts of NSAIDs. The researchers had limited ability to detect risks of meloxicam, naproxen, and traditional NSAIDs because most NSAID prescriptions were for rofecoxib and celecoxib. The researchers may have missed some heart attacks since the study databases recorded only heart attacks that led to hospitalization.

What are the implications of the study?

Some nonselective NSAIDs and COX-2 inhibitors, other than rofecoxib, might not increase the risk for a heart attack.