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

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

  • International Clinical Digest
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Takeaway

  • 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  • Most trials were of celecoxib; fewer investigated etoricoxib (not approved by the FDA) and rofecoxib (FDA approval withdrawn in 2004, as was the European Medicines Agency's approval).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%).

Limitations

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

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