There have been concerns that the risk of cardiovascular thrombotic events may be higher with
cyclooxygenase (COX)-2-specific inhibitors than nonselective nonsteroidal antiinflammatory drugs (
NSAIDs). We evaluated cardiovascular event data for
valdecoxib, a new COX-2-specific inhibitor in approximately 8000 patients with
osteoarthritis and
rheumatoid arthritis treated with this agent in randomized clinical trials. The incidence of cardiovascular thrombotic events (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was determined by analyzing pooled
valdecoxib (10-80 mg daily), nonselective
NSAID (
diclofenac 75 mg bid,
ibuprofen 800 mg tid, or
naproxen 500 mg bid) and placebo data from 10 randomized
osteoarthritis and
rheumatoid arthritis trials that were 6-52 weeks in duration. The incidence rates of events were determined in all patients (n = 7934) and in users of low-dose (< or =325 mg daily)
aspirin (n = 1051) and nonusers of
aspirin (n = 6883). Crude and exposure-adjusted incidences of thrombotic events were similar for
valdecoxib,
NSAIDs, and placebo. The risk of serious thrombotic events was also similar for each
valdecoxib dose. Thrombotic risk was consistently higher for users of
aspirin users than nonusers of
aspirin (placebo, 1.4% vs. 0%;
valdecoxib, 1.7% vs. 0.2%;
NSAIDs, 1.9% vs. 0.5%). The rates of events in users of
aspirin were similar for all 3 treatment groups and across
valdecoxib doses. Short- and intermediate-term treatment with therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily)
valdecoxib doses was not associated with an increased incidence of thrombotic events relative to nonselective
NSAIDs or placebo in
osteoarthritis and
rheumatoid arthritis patients in controlled clinical trials.