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).
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%).