NSAIDs and cox-2 inhibitors

The unexpected withdrawal of Vioxx in September 2004, followed by Bextra in April 2005, has led many physicians to reassess the place of selective cox-2 inhibitors in pain management. These concerns were heightened last spring when the FDA applied the same "black box warning" to all NSAIDs as well, cautioning that they each can increase the risk of cardiovascular events. What is really known about the comparative efficacy and safety of these drugs?

The overwhelming evidence from clinical trials shows that selective cox-2 inhibitors do not have any stronger analgesic efficacy than conventional NSAIDs such as noproxen or ibuprofen.1

The main advantage of drugs like rofecoxib (Vioxx) or celecoxib (Celebrex) was the expectation that they would lower the risk of gastrointestinal bleeding compared to older NSAIDs. However,

  • this protection was relative, not absolute,2,3
  • concurrent use of low-dose aspirin for cardioprotection can sharply reduce the g.i. protection offered by these drugs,2
  • only a small portion of patients who will need chronic analgesics are at high risk of NSAID-induced g.i. bleeding in the first place,4
  • there are other effective ways of protecting patients from analgesic-induced g.i. side effects, such as adding a proton pump inhibitor to a conventional NSAID.5

Which patients are at most risk for g.i. side effects?

  • older age,
  • history of peptic ulcer disease,
  • using oral steroids,
  • taking warfarin (Coumadin) or another anticoagulant.

Pain specialists and rheumatologists recommend the following approach for pain management:6

  • Start with acetaminophen.
  • Naproxen is probably the safest NSAID in terms of cardiac risk.
  • All patients who require cardioprotective use of low-dose aspirin should receive it regardless of their NSAID regimen.
  • Whatever regimen is chosen, prescribe the lowest dose that will control pain, and the shortest duration of therapy. Monitor patients for side effects including fluid retention, hypertension, reduction in renal function, and evidence of gastrointestinal toxicity.

Who really needs a cox-2 inhibitor?

  • The approach recommended above will work best for most patients.
  • Data suggest that Celebrex be reserved for patients who require an NSAID, are at increased risk of g.i. complications, and cannot tolerate the suggested regimens.7

For patients with chronic arthritis pain, rheumatologists recommend several additional strategies to avoid having to commit a patient to years of high-dose NSAID therapy.6

  • Protect the affected joints with a cane, brace, weight loss, and lower extremity exercise programs.
  • Evaluate the need for controlled opioid analgesics in carefully selected patients.
  • Don't wait too long before surgery in patients with severe osteoarthritis, for which the most effective treatment may be joint replacement.

These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient's clinical condition.


  1. Helfand M, Peterson K, Carson SM. Drug class review on NSAIDs. Final Report: http://www.ohsu.edu (updated November 2006).
  2. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial.  Journal of the American Medical Association. 2000;284(10):1247-1255.
  3. Bombardier C, Laine L, Reicin A, et al. VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. New England Journal of Medicine. 2000;343(21):1520-1528.
  4. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Annals of Internal Medicine. 1991;115(10):787-796.
  5. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. New England Journal of Medicine. 2002;347(26):2104-2110.
  6. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis and Rheumatism. 2000;43(9):1905-1915.
  7. Solomon DH. Selective cyclooxygenase 2 inhibitors and cardiovascular events. Arthritis and Rheumatism. 2005;52(7):1968-1978.