Level 1: Likely reliable evidence
The Adenoma Prevention with Celecoxib (APC) trial evaluated 2,035 patients with a prior history of colorectal adenoma who were randomized to placebo vs. celecoxib (Celebrex) 200 mg vs. celecoxib 400 mg twice daily for three years (N Engl J Med. 2006;355:873-884). Rates of colonoscopy were 89% at one year and 76% at three years; 10.5% of patients did not complete the study.
Celecoxib reduced the rate of recurrent adenomas. The estimated incidence of recurrent adenomas at three years was 60.7% with placebo vs. 43.2% with celecoxib 200 mg twice daily (NNT 6) vs. 37.5% with celecoxib 400 mg twice daily (NNT 5). In an intention-to-treat analysis assuming no adenomas when no colonoscopy was done, the rates were 52.1% with placebo vs. 36.8% with celecoxib 200 mg twice daily (NNT 7) vs. 31.7% with celecoxib 400 mg twice daily (NNT 5).
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Despite the seemingly positive effects of celecoxib, the study was terminated early due to increased risk for cardiovascular (CV) events with the COX-2 inhibitor. The composite CV end point (death from CV causes, MI, stroke, or heart failure) was reached in 1% of placebo patients compared with 2.6% of patients taking celecoxib 200 mg twice daily (NNH 62) and 3.4% of patients taking celecoxib 400 mg twice daily (NNH 41). Using a more broadly defined CV end point (also including angina, peripheral vascular disease, vascular procedures, and venous thromboembolism), the rates were 4.4% in placebo patients vs. 6.6% in celecoxib 200 mg twice-daily patients (not statistically significant) vs. 8.1% in celecoxib 400 mg twice daily patients (NNH 27). The rate of overall death did not reach statistical significance but was higher with celecoxib (0.9% vs. 1.2% vs. 1.5%).
