Osteoarthritis: COX-2 inhibitors tied to upper GI, cardiovascular risks

  • Curtis E & al.
  • Drugs Aging
  • 1 Apr 2019

  • International Clinical Digest
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.


  • Cyclooxygenase-2 (COX-2) inhibitors for osteoarthritis (OA) are associated with elevated risk for upper gastrointestinal (GI) and cardiovascular adverse events (AEs), with heart failure and edema carrying the greatest increased risk (nearly 70% vs placebo).

Why this matters

  • Authors advise limiting COX-2 inhibitors to intermittent or cyclical use, rather than chronic use.

Study design

  • Meta-analysis of 40 randomized, placebo-controlled trials, after a search of MEDLINE, Cochrane Central Register, and Scopus.
  • Most trials were of celecoxib; fewer investigated etoricoxib (not approved by the FDA) and rofecoxib (FDA approval withdrawn in 2004, as was the European Medicines Agency's approval).
  • Funding: European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Disorders.

Key results

  • COX-2 inhibitors (vs placebo) were associated with increased risk for:
    • Overall AEs (relative risk [RR], 1.26; 95% CI, 1.09-1.46; I2=24%).
    • Upper GI complications (including dyspepsia, gastritis, and heartburn; RR, 1.19; 95% CI, 1.03-1.38; I2=0%), especially abdominal pain (RR, 1.40; 95% CI, 1.08-1.80; I2=0%).
    • Hypertension (RR, 1.45; 95% CI, 1.01-2.10; I2=25%), but not when rofecoxib was excluded from analysis (RR, 1.21; 95% CI, 0.80-1.83; I2=20%).
    • Heart failure and edema (RR, 1.68; 95% CI, 1.22-2.31; I2=0%), which remained similarly significant when rofecoxib was excluded (RR, 1.67; 95% CI, 1.21-2.29; I2=0%).


  • Half of trials did not report AEs.
  • Moderate heterogeneity for some outcomes.
  • Total number of participants not reported.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.