NSAIDs and cardiovascular risk


Clinical question: Which NSAID confers the least cardiovascular risk?

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation by decreasing prostaglandin production through cyclo-oxygenase (COX) inhibition. However, the COX enzyme stimulates protective prostaglandins for the GI mucosa. The development of cyclo-oxygenase-2 (COX-2) inhibitors did reduce the gastrointestinal side effects of NSAIDs, but subsequent trials pointed to increased cardiovascular events and resulted in rofecoxib being removed from the market. Celecoxib remained on the market as the only COX-2 inhibitor, but the Food and Drug Administration required a cardiovascular safety trial.

Study design: Prospective randomized, double-blind noninferiority study.

Setting: International (926 centers in 13 countries).

Synopsis: The PRECISION trial enrolled 24,081 patients who required NSAIDs for arthritis pain and who either had established cardiovascular disease or an increased risk of CV disease. Patients were randomized to celecoxib 100 mg twice a day, ibuprofen 600 mg three times a day, or naproxen 375 mg twice a day. Patients were allowed to continue taking low-dose aspirin (325 mg or less daily). The primary composite outcome was cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. A secondary composite outcome was major adverse CV events (the primary outcome plus coronary revascularization or hospitalization for unstable angina or transient ischemic attack) and significant gastrointestinal events.

The primary outcome occurred in 188 patients in the celecoxib group (2.3%), 201 in the naproxen group (2.5%), and 218 in the ibuprofen group (2.7%). Celecoxib, as compared with either naproxen or ibuprofen, met all four prespecified noninferiority requirements (P less than .01 for noninferiority in both comparisons. Ibuprofen, as compared with naproxen, just met the noninferiority criteria (P = .025).

Bottom line: The PRECISION trial provides statistically strong evidence that the cardiovascular risk associated with moderate doses of celecoxib is not greater than that associated with nonselective NSAIDs (ibuprofen and naproxen).

Citations: Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis.” N Engl J M. 2016;375(26):2519-2529.

Dr. Cerceo is an assistant professor in the Division of Hospital Medicine, and associate director of the internal medicine residency program at Cooper Medical School of Rowan University, Camden, N.J.

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