OBJECTIVES: Selective
cyclooxygenase (COX)-2 inhibitors are effective
analgesic and
anti-inflammatory agents with improved gastrointestinal safety and tolerability compared with traditional
NSAIDs. However, data from long-term, placebo-controlled studies have shown an increased risk of thrombotic cardiovascular (CV) events for
COX-2 inhibitors. Changes in levels of CV
biomarkers are potentially useful surrogate measures of pathologic changes associated with CV risk. METHODS: We randomized 433 patients with
osteoarthritis to
etoricoxib 90 mg once daily,
celecoxib 200 mg twice daily,
ibuprofen 800 mg three times daily, or placebo for 12 weeks. The hypothesis was that
etoricoxib would be non-inferior or superior to placebo in effect on
C-reactive protein (CRP),
LDL-cholesterol,
homocysteine, and
fibrinogen. RESULTS: Relative to placebo,
etoricoxib was noninferior for effect on CRP (decreased 7.8% vs. placebo; 97.5% CI of the difference: -30.5, 22.4),
LDL-C (-4.0% vs. placebo; 97.5% CI: -10.6, 3.2),
homocysteine (-3.9% vs. placebo; 97.5% CI: -11.6, 4.6), and
fibrinogen (-3.7% vs. placebo; 97.5% CI: -9.4, 2.3).
Etoricoxib was not different from placebo,
celecoxib, or
ibuprofen for any
biomarker. CONCLUSION:
Etoricoxib was comparable to placebo,
celecoxib, and
ibuprofen for effects on the CV risk markers measured.