Cardiovascular Safety of Celecoxib

Summary and Comment |
November 14, 2016

Cardiovascular Safety of Celecoxib

  1. Allan S. Brett, MD

In a randomized trial, 100 mg (taken twice daily) was not inferior to naproxen and ibuprofen for cardiovascular safety.

  1. Allan S. Brett, MD

In previous randomized trials, daily doses of 400 mg to 800 mg of the selective cyclooxygenase (COX)-2 inhibitor celecoxib (Celebrex and generic) raised risk for adverse cardiovascular (CV) events compared with placebo (NEJM JW Gen Med Mar 15 2005 and N Engl J Med 2005; 352:1071; NEJM JW Gen Med Sep 15 2006 and N Engl J Med 2006; 355:873). In contrast, naproxen is believed to have the safest CV profile among nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). In this randomized, double-blind study, researchers compared celecoxib (100 mg twice daily), naproxen (375 mg twice daily), and ibuprofen (600 mg thrice daily) in 24,000 patients with osteoarthritis or rheumatoid arthritis. All patients had known CV disease, diabetes, or multiple CV risk factors. The study was designed to test whether celecoxib was noninferior to the other two drugs for a primary outcome of CV death, nonfatal myocardial infarction, or nonfatal stroke. The manufacturer of Celebrex sponsored this trial.

Mean treatment duration was 20 months; mean follow-up was 34 months. In intent-to-treat analysis, the incidence of the primary CV outcome was 2.3%, 2.5%, and 2.7% in the celecoxib, naproxen, and ibuprofen groups, respectively — demonstrating noninferiority of celecoxib. On-treatment analysis yielded similar results. For symptomatic gastrointestinal events (i.e., gastroduodenal ulcer and complications), intent-to-treat analysis showed no significant differences between groups, but celecoxib recipients were less likely to develop iron-deficiency anemia of gastrointestinal origin (about 4 fewer cases per 1000 patients).


At a dose of 100 mg twice daily, celecoxib did not confer greater CV risk than naproxen or ibuprofen. However, this outcome should not be interpreted as proving CV safety, because no untreated control group was available for comparison. Therefore, the trial shouldn't change clinical practice: Patients at high CV risk generally should avoid use of celecoxib or traditional NSAIDs. When these drugs must be used, either a nonselective NSAID plus a proton-pump inhibitor or celecoxib is appropriate in patients at risk for gastrointestinal complications — but keep in mind that the cash cost of celecoxib (both Celebrex and generic) is still several hundred dollars monthly. A detailed commentary on PRECISION, written by a highly regarded authority on NSAIDs and published in Circulation, explains the history of this trial and gives additional compelling reasons why its results should not be construed as necessarily favorable to celecoxib.

Editor Disclosures at Time of Publication

  • Disclosures for Allan S. Brett, MD at time of publication Nothing to disclose


Reader Comments (2)

Lawrence Cohn Physician, Psychiatry, OFFICE PINECREST, FL


Jorge Bejarano Physician, Internal Medicine, Medellin Colombia

Celecoxib is quite useful medicación, but it is difficult for me to believe this , knowing in advance this trial is sponsored by its manufacturer, can we have another source?

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