Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial
Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial
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DOI：
10.1016/s0140-6736(04)16894-3
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发表时间：
2004-08-21
期刊：
影响因子：
168.9
通讯作者：
Chesebro, JH
中科院分区：
文献类型：
--
作者：
Farkouh, ME;Kirshner, H;Chesebro, JH
背景 环加氧酶 2 (COX2) 选择性抑制剂增加心肌梗死风险的可能性存在争议。治疗性关节炎研究和胃肠道事件试验 (TARGET) 旨在评估 COX2 抑制剂 lumiracoxib 与两种非甾体类抗炎药（萘普生和布洛芬）相比的胃肠道和心血管安全性。方法 18 325 名 50 岁或以上患有骨关节炎的患者被随机分配至 lumiracoxib 400 mg 每天一次 (n=9156)、萘普生在两项设计相同的子研究中，每天两次 500 毫克 (4754) 或每天三次 800 毫克布洛芬 (4415)。根据低剂量阿司匹林的使用和年龄对随机分组进行分层。主要心血管终点是非致命性和无症状心肌梗塞、中风或心血管死亡的抗血小板试验者合作终点。按意向治疗进行分析。结果显示，81 名患者 (0.44%) 没有开始治疗，7120 名患者 (39%) 没有完成研究。 1 年随访时，罗美昔布（59 起事件 [0.65%]）和非甾体类抗炎药（50 起事件 [0.55%]；风险比 1.14 [95% CI 0.78-1.66]，p=0.5074）的主要终点发生率较低。在各个亚组研究中，总人群中心肌梗死（临床和无症状）的发生率为 0.38%（18 起），而萘普生（10 起）为 0.21%，罗美昔布（5 起）为 0.11%，布洛芬（7 起）为 0.16%。在萘普生子研究中，与罗美昔布相比，在未服用低剂量阿司匹林的人群中，心肌梗死（临床和无症状）发生率没有显着差异（风险比为 2.37 [95% CI 0.74-7.55]，p=0.1454），总体（1.77 [0.82-3.84]，p=0.1471），以及在服用低剂量阿司匹林的患者中阿司匹林（1.36 [0.47-3.93]，p=0.5658）。在布洛芬子研究中，在未服用低剂量阿司匹林的人群中（0.75 [0.20-2.79]，p=0.6669）、总体人群（0.66 [0.21-2.09]，p=0.4833）和服用阿司匹林的患者中（0.47），罗美昔布和布洛芬之间的这些比率没有差异。 [0.04-5.14]，p=0.5328）。解释 无论是否使用阿司匹林，罗美昔布与布洛芬或萘普生之间的主要终点（包括心肌梗塞发生率）没有差异。这一发现表明，罗美昔布是骨关节炎患者的适当治疗方法，这些患者通常具有较高的心血管风险并服用小剂量阿司匹林。
Background The potential for cyclo-oxygenase 2 (COX2)-selective inhibitors to increase the risk for myocardial infarction is controversial. 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) in two substudies of identical design. Randomisation was stratified for low-dose aspirin use and age. The primary cardiovascular endpoint was the Antiplatelet Trialists' Collaboration endpoint of non-fatal and silent myocardial infarction, stroke, or cardiovascular death. Analysis was by intention to treat.Findings 81 (0.44%) patients did not start treatment and 7120 (39%) did not complete the study. At 1-year follow-up, incidence of the primary endpoint was low, both with lumiracoxib (59 events [0.65%]) and the non-steroidal anti-inflammatory drugs (50 events [0.55%]; hazard ratio 1.14 [95% CI 0.78-1.66], p=0.5074). Incidence of myocardial infarction (clinical and silent) in the overall population in the individual substudies was 0.38% with lumiracoxib (18 events) versus 0.21% with naproxen (ten) and 0.11% with lumiracoxib (five) versus 0.16% with ibuprofen (seven). In the naproxen substudy, rates of myocardial infarction (clinical and silent) did not differ significantly compared with lumiracoxib in the population not taking low-dose aspirin (hazard ratio 2.37 [95% CI 0.74-7.55], p=0.1454), overall (1.77 [0.82-3.84], p=0.1471), and in patients taking aspirin (1.36 [0.47-3.93], p=0.5658). In the ibuprofen substudy, these rates did not differ between lumiracoxib and ibuprofen in the population not taking low-dose aspirin (0.75 [0.20-2.79], p=0.6669), overall (0.66 [0.21-2.09], p=0.4833), and in patients taking aspirin (0.47 [0.04-5.14], p=0.5328).Interpretation The primary endpoint, including incidence of myocardial infarction, did not differ between lumiracoxib and either ibuprofen or naproxen, irrespective of aspirin use. This finding suggests that lumiracoxib is an appropriate treatment for patients with osteoarthritis, who are often at high cardiovascular risk and taking low-dose aspirin.