Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Risk of NSAID Toxicity in Patients with Arthritis

Am J Med; ePub 2017 Jul 26; Solomon, et al

Patients with symptomatic arthritis with moderate to high risk of cardiovascular events and taking a nonsteroidal anti-inflammatory (NSAID) had an increased risk of major toxicity, with users of naproxen or ibuprofen experiencing a significantly higher risk than users of celecoxib. This according to a secondary analysis of the PRECISION randomized controlled clinical trial that included 24,081 patients with osteoarthritis or rheumatoid arthritis at moderate or high CV risk. Patients were randomized to receive celecoxib 100-200 mg twice daily, ibuprofen 600-800 mg thrice daily, or naproxen 375-500 mg twice daily. All patients were provided with a proton pump inhibitor. Researchers found:

  • Overall, ∼1 in 20 patients experienced major toxicity over 1 to 2 years.
  • During follow-up, 4.1% of patients in the celecoxib arm sustained any major toxicity, 4.8% in the naproxen arm, and 5.3% in the ibuprofen arm.
  • Adjustment for aspirin use and geographic region found that participants in the naproxen arm had a 19% higher risk of major toxicity than celecoxib users and ibuprofen users had a 41% higher risk.


Solomon DH, Husni ME, Libby PA, et al. The risk of major NSAID toxicity with celecoxib, ibuprofen or naproxen: a secondary analysis of the PRECISION randomized controlled clinical trial. [Published online ahead of print July 26, 2017]. Am J Med. doi:10.1016/j.amjmed.2017.06.028.


NSAIDs are among the most commonly used medications, so knowing the differences in the risk of varying medications in this class is important. This study was a secondary analysis of the PRECISION trial, which looked at patients with osteoarthritis and rheumatoid arthritis who were at moderate CV risk or had established CV disease who were then randomized to celecoxib, ibuprofen or naproxen. The PRECISION trial concluded that celecoxib did not cause more CV events than ibuprofen or naproxen.1 This subgroup analysis looked at total major toxicity, which in addition to major cardiovascular events, included clinically important gastrointestinal events (GI bleeds or symptomatic ulcers), renal events (development of renal insufficiency or failure), and all-cause mortality. This trial shows the non-selective NSAIDs naproxen and ibuprofen had significantly higher risk of major NSAID toxicity than celecoxib. —Neil Skolnik, MD

  1. Becker MC, Wang TH, Wisniewski L, et al. Rationale, design, and governance of prospective randomized evaluation of celecoxib integrated safety versus ibuprofen or naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal anti-inflammatory agents in patients with arthritis. Am Heart J. 2009;157(4):606-612. doi:10.1016/j.ahj.2008.12.014.