Celecoxib Associated With Lower MACE Risk Than Naproxen and Ibuprofen

Patients taking celecoxib for arthritis who were at risk for cardiovascular events experienced better safety outcomes than with naproxen or ibuprofen.

A study in the Journal of the American College of Cardiology showed that the nonsteroidal anti-inflammatory drug (NSAID) celecoxib imparted better safety outcomes in patients with arthritis who were at risk for cardiovascular events than naproxen or ibuprofen. Specifically, celecoxib without aspirin therapy is associated with fewer gastrointestinal, renal, and cardiovascular events than naproxen or ibuprofen.

In the post hoc analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen; ClinicalTrials.gov Identifier: NCT00346216) trial, investigators evaluated a total of 23,953 patients with osteoarthritis or rheumatoid arthritis who were at risk for cardiac events.

Investigators randomly assigned patients to either 100 to 200 mg twice-daily celecoxib (n=8030), 600 to 800 mg 3-times-daily ibuprofen (n=7990), or 375 to 500 mg twice-daily naproxen (n=7933). Investigators also stratified their analysis by patients who used aspirin (n=11,018) vs those who did not use aspirin (n=12,935) at time of randomization. Outcomes analyzed included a composite of major adverse cardiovascular events (MACE), noncardiovascular death, gastrointestinal or renal events, and composite components.

In the non-aspirin group, patients taking naproxen had a significantly greater risk for the primary composite MACE outcome compared with patients taking celecoxib (adjusted hazard ratio [HR], 1.52; 95% CI, 1.22-1.90; P <.001). This higher MACE risk was also observed in patients taking ibuprofen (adjusted HR, 1.81; 95% CI, 1.46-2.26; P <.001). Ibuprofen was associated with greater numbers of cardiovascular events compared with celecoxib (P <.05), and ibuprofen and naproxen combined resulted in more gastrointestinal (P <.001) and renal (P <.05) events.

Ibuprofen was also associated with a greater risk for the primary composite outcome than celecoxib when aspirin was added to therapy (adjusted HR, 1.27; 95% CI, 1.06-1.51; P <.01). In the pooled analysis, patients taking aspirin experienced similar rates of MACE with all NSAIDs (adjusted HR, 1.10; 95% CI, 0.97-1.25; P =.13). Patients taking aspirin who were randomly assigned to ibuprofen also experienced more gastrointestinal and renal events compared with those taking celecoxib (P <.05), and naproxen resulted in a greater number of gastrointestinal events only (P <.05).

PRECISION was not designed to detect an interaction between the trial NSAIDs and aspirin, and therefore the current analysis should be considered hypothesis generating. The inclusion of only moderate NSAID doses may also limit the analysis.

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Findings from the study indicate “that in many cases, celecoxib would be preferred to naproxen or ibuprofen, especially if the patient is not required to take aspirin.”


Reed GW, Abdallah MS, Shao M, et al. Effect of aspirin coadministration on the safety of celecoxib, naproxen, or ibuprofen. J Am Coll Cardiol. 2018;71(16):1741-1751.