Cardiac Risk With COX-2 and NSAID Drugs

New study shows that not all of these drugs impart the same level of risk

As anyone who has been reading the papers for the last few years knows, COX-2 drugs - a group of non-steroidal drugs used to treat inflammation and pain - have been associated with an increased incidence of heart attack and other cardiovascular events. Most notably, the drug company Merck has been in the papers frequently since 2004 for one lawsuit or another associated with its COX-2 drug Vioxx (rofecoxib). Furthermore, studies have have suggested that it's not only the COX-2 drugs that are a problem, and that even the older non-steroidal anti-inflammatory drugs (NSAIDs) may pose increased cardiac risk. (Technically, COX-2 drugs are a sub-category of NSAIDs.)

An analysis of available data from several studies now strongly suggests that most COX-2 drugs and NSAIDs worsen cardiac outcomes in people who have heart disease or have increased risk for heart disease, but these drugs are not all equally dangerous. In fact, one drug -- naproxen (Aleve, Naprosyn) -- may not increase cardiac risk at all.

The latest study, published in 2009, retrospectively analyzed the use of COX-2 drugs and NSAIDS in more than 48,000 patients with coronary artery disease, and tabulated the subsequent incidence of heart attack or cardiac death. This is the largest study currently published. There are no randomized trials examining the relationship between NSAIDs and cardiac risk as yet, and none are expected to be reported until 2011. However, based on the information available to date, the following generalizations can be made:

Drugs that seem very likely to increase risk: ibuprofen (Advil, Motrin), Voltaren (diclofenac), Indocin (indomethacin), and Mobic (meloxicam). Of these drugs, it appears -- at this point -- that Voltaren may increase cardiac risk more than the others.

Drugs that may increase risk: VIOXX and Celebrex (celecoxib). (Some data suggests that, while Celebrex probably increases cardiac risk at high doses, at more routine doses -- up to 200 mg/day -- there is little evidence for increased risk.)

Drugs that appear not to increase risk, or may reduce risk: naproxen

Given all the publicity that COX-2 drugs have received, and especially because VIOXX was taken off the market because of presumed cardiac risk, it is at least a little bit interesting that some of the older, more commonly-used NSAIDs now appear to increase risk to even a greater extent.

The bottom line is that, until randomized trials are completed -- which should offer more definitive evidence as to the magnitude of cardiac risk with NSAIDs -- naproxen is probably the best choice if a NSAID is needed when cardiovascular risk is a concern.

_Sources:

_{Graham DJ. COX-2 Inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA2006; DOI:10.1001/JAMA.296.13.jed60058. See: http://www.jama.com.}

_{Ray WA, Varas-Lorenzo C, Chung CP, et al. Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes 2009; 2:155-163.}

_{McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase-2. JAMA2006; DOI: 10.1001/JAMA.296.13.jrv60011. See: http://www.jama.com.}