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- Most trials were of celecoxib; fewer investigated etoricoxib (not approved by the FDA) and rofecoxib (FDA approval withdrawn in 2004, as was the European Medicines Agency's approval).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