Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial
Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial
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DOI：
10.1016/s0140-6736(04)16893-1
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发表时间：
2004-08-21
期刊：
影响因子：
168.9
通讯作者：
Hawkey, CJ
中科院分区：
文献类型：
--
作者：
Schnitzer, TJ;Burmester, GR;Hawkey, CJ
背景与非选择性非甾体抗炎药相比，选择性环氧合酶2(COX2)抑制剂应该可以减少溃疡并发症，但证据有限，而且这些抑制剂增加心血管事件的可能性已经被提出。治疗关节炎研究和胃肠道事件试验(TARGET)旨在评估COX2抑制剂鲁米拉昔布与两种非类固醇抗炎药萘普生和布洛芬的胃肠和心血管安全性。方法18 325名50岁或50岁以上的骨关节炎患者随机分为卢米拉昔布400 mg每日1次(n=9156)、萘普生500 mg每日2次(4754)或布洛芬800 mg每日3次(4415)，为期52周。对小剂量阿司匹林的使用和年龄进行了分层随机分组。主要终点是上消化道溃疡并发症(出血、穿孔或梗阻)的事件发生时间分布的差异；分析采用改良的治疗意图。不良心血管事件的主要衡量标准是抗血小板试验的协作终点(心肌梗死、中风或心血管死亡)；这项分析是为了治疗。结果81名患者(0.44%)没有开始治疗，7120名(39%)没有完成研究。在未服用阿司匹林的患者中，服用非类固醇抗炎药(事件)的患者1年内溃疡并发症的累积发生率为1.09%(95%可信区间0.82~1.36)，而服用鲁米拉昔布的患者(发生14起事件，风险比0.21[95%可信区间0.12~0.37]，P<0.05)。
Background Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with nonselective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen.Methods 18 325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib vs ibuprofen or naproxen). Randomisation was stratified for low-dose aspirin use and age. The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction); analysis was by modified intention to treat. The principle measure of adverse cardiovascular events was the Antiplatelet Trialists' Collaboration endpoint (myocardial infarction, stroke, or cardiovascular death); this analysis was intention to treat.Findings 81 (0.44%) patients did not start treatment and 7120 (39%) did not complete the study. In patients not taking aspirin, the cumulative 1-year incidence of ulcer complications was 1.09% (95% Cl 0.82-1.36) with nonsteroidal anti-inflammatory drugs (64 events) versus 0.25% (95% CI 0.12-0.39) with lumiracoxib (14 events; hazard ratio 0.21 [95% CI 0.12-0.37], p