Chan Francis Ka Leung, Wong Vincent Wai Sun, Suen Bing Yee, Wu Justin Che Yuen, Ching Jessica Yuet Ling, Hung Lawrence Cheung Tsui, Hui Aric Josun, Leung Vincent King Sun, Lee Vivian Wing Yan, Lai Larry Hin, Wong Grace Lai Hung, Chow Dorothy Kai Lai, To Ka Fa, Leung Wai Keung, Chiu Philip Wai Yan, Lee Yuk Tong, Lau James Yun Wong, Chan Henry Lik Yuen, Ng Enders Kwok Wai, Sung Joseph Jao Yiu
Institute of Digestive Disease, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Lancet. 2007 May 12;369(9573):1621-6. doi: 10.1016/S0140-6736(07)60749-1.
Guidelines 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.
441 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.
Combination 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.
Patients 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.
疼痛管理指南建议，有溃疡风险的患者应服用环氧化酶（COX-2）抑制剂或非甾体抗炎药（NSAID）加质子泵抑制剂（PPI）。这两种治疗方法效果相似，但对于溃疡出血高风险患者的保护作用不足。我们旨在验证以下假设：对于既往因非选择性NSAID导致溃疡出血的患者，联合使用COX-2抑制剂塞来昔布和PPI埃索美拉唑预防复发性溃疡出血的效果优于单用塞来昔布。
441例因关节炎正在服用非选择性NSAID且因上消化道出血入院的患者被纳入我们的单中心、前瞻性、随机、双盲试验。患者在溃疡愈合且幽门螺杆菌组织学检测为阴性后入组。所有患者每日两次服用200mg塞来昔布。137例患者被随机分配至每日两次服用20mg埃索美拉唑组（联合治疗组），136例患者被分配至服用安慰剂组（对照组），为期12个月。主要终点为治疗期间或治疗结束后1个月内复发性溃疡出血。分析采用意向性分析。本试验已在ClinicalTrials.gov注册，注册号为NCT00365313。
联合治疗在预防高危患者溃疡出血方面比单用塞来昔布更有效。联合治疗组主要终点的13个月累积发生率为0%，对照组为12例（8.9%）（95%CI差值，4.1至13.7；p=0.0004）。中位随访时间为13个月（范围0.4 - 13.0）。两个治疗组的治疗中断率和不良事件发生率相似。
对于复发性溃疡出血高风险且需要抗炎镇痛的患者，应接受COX-2抑制剂和PPI的联合治疗。我们的研究结果应促使指南委员会重新审视其针对复发性溃疡出血高风险患者的建议。
