• Francis Ka Leung Chan, Vincent Wai Sun Wong, Bing Yee Suen, Justin Che Yuen Wu, Jessica Yuet Ling Ching, Lawrence Cheung Tsui Hung, Aric Josun Hui, Vincent King Sun Leung, Vivian Wing Yan Lee, Larry Hin Lai, Grace Lai Hung Wong, Dorothy Kai Lai Chow, Ka Fa To, Wai Keung Leung, Philip Wai Yan Chiu, Yuk Tong Lee, James Yun Wong Lau, Henry Lik Yuen Chan, Enders Kwok Wai Ng, and Joseph Jao Yiu Sung.
• Institute of Digestive Disease, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. fklchan@cuhk.edu.hk
• Lancet. 2007 May 12;369(9573):1621-6.

BackgroundGuidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding.Methods441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00365313.FindingsCombination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI difference, 4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups.InterpretationPatients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.

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