Schnitzer Thomas J, Burmester Gerd R, Mysler Eduardo, Hochberg Marc C, Doherty Michael, Ehrsam Elena, Gitton Xavier, Krammer Gerhard, Mellein Bernhard, Matchaba Patrice, Gimona Alberto, Hawkey Christopher J
Office of Clinical Research and Training, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Lancet. 2004;364(9435):665-74. doi: 10.1016/S0140-6736(04)16893-1.
Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective 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.
18325 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.
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% CI 0.82-1.36) with non-steroidal 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<0.0001). Reductions in ulcer complications were also significant in the overall population (0.34 [0.22-0.52], p<0.0001) but not in those taking aspirin (0.79 [0.40-1.55], p=0.4876). In the overall population, 0.55% (50/9127) of those on non-steroidal anti-inflammatory drugs and 0.65% (59/9117) of those on lumiracoxib reached the cardiovascular endpoint (1.14 [0.78-1.66], p=0.5074).
Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis.
与非选择性非甾体抗炎药相比，环氧化酶2（COX2）选择性抑制剂应能降低溃疡并发症的发生，但证据有限，且有人提出这些抑制剂可能会增加心血管事件的发生风险。治疗性关节炎研究与胃肠道事件试验（TARGET）旨在评估COX2抑制剂鲁米昔布与两种非甾体抗炎药萘普生和布洛芬相比的胃肠道及心血管安全性。
18325例年龄在50岁及以上的骨关节炎患者被随机分为三组，分别每日一次服用鲁米昔布400mg（n = 9156）、每日两次服用萘普生500mg（4754例）或每日三次服用布洛芬800mg（4415例），疗程为52周，共进行两项设计相同的亚研究（鲁米昔布分别与布洛芬或萘普生对比）。随机分组根据低剂量阿司匹林使用情况和年龄进行分层。主要终点为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差异；分析采用改良意向性治疗。不良心血管事件的主要衡量指标为抗血小板试验协作组终点（心肌梗死、中风或心血管死亡）；此分析为意向性治疗。
81例（0.44%）患者未开始治疗，7120例（39%）未完成研究。在未服用阿司匹林的患者中，非甾体抗炎药组溃疡并发症的累积1年发生率为1.09%（95%可信区间0.82 - 1.
