Cannon Christopher P, Chen Cong, Curtis Sean P, Viscusi John, Ahmed Tuli, Dibattiste Peter M
Arch Drug Inf. 2008 Jul;1(1):4-13. doi: 10.1111/j.1753-5174.2007.00002.x.
Selective cyclooxygenase (COX)-2 inhibitors are effective analgesic and anti-inflammatory agents with improved gastrointestinal safety and tolerability compared with traditional NSAIDs. However, data from long-term, placebo-controlled studies have shown an increased risk of thrombotic cardiovascular (CV) events for COX-2 inhibitors. Changes in levels of CV biomarkers are potentially useful surrogate measures of pathologic changes associated with CV risk. METHODS: We randomized 433 patients with osteoarthritis to etoricoxib 90 mg once daily, celecoxib 200 mg twice daily, ibuprofen 800 mg three times daily, or placebo for 12 weeks. The hypothesis was that etoricoxib would be non-inferior or superior to placebo in effect on C-reactive protein (CRP), LDL-cholesterol, homocysteine, and fibrinogen. RESULTS: Relative to placebo, etoricoxib was noninferior for effect on CRP (decreased 7.8% vs. placebo; 97.5% CI of the difference: -30.5, 22.4), LDL-C (-4.0% vs. placebo; 97.5% CI: -10.6, 3.2), homocysteine (-3.9% vs. placebo; 97.5% CI: -11.6, 4.6), and fibrinogen (-3.7% vs. placebo; 97.5% CI: -9.4, 2.3). Etoricoxib was not different from placebo, celecoxib, or ibuprofen for any biomarker. CONCLUSION: Etoricoxib was comparable to placebo, celecoxib, and ibuprofen for effects on the CV risk markers measured.
与传统非甾体抗炎药相比，选择性环氧化酶（COX）-2抑制剂是有效的镇痛和抗炎药物，具有更好的胃肠道安全性和耐受性。然而，长期安慰剂对照研究的数据显示，COX-2抑制剂会增加血栓性心血管（CV）事件的风险。CV生物标志物水平的变化可能是与CV风险相关的病理变化的有用替代指标。方法：我们将433例骨关节炎患者随机分为四组，分别每日一次服用90毫克依托考昔、每日两次服用200毫克塞来昔布、每日三次服用800毫克布洛芬或服用安慰剂，为期12周。假设是依托考昔在对C反应蛋白（CRP）、低密度脂蛋白胆固醇、同型半胱氨酸和纤维蛋白原的作用上不劣于或优于安慰剂。结果：相对于安慰剂，依托考昔在对CRP（降低7.8% vs.安慰剂；差异的97.5%置信区间：-30.5，22.4）、低密度脂蛋白胆固醇（-4.0% vs.安慰剂；97.5%置信区间：-10.6，3.2）、同型半胱氨酸（-3.9% vs.安慰剂；97.5%置信区间：-11.6，4.6）和纤维蛋白原（-3.7% vs.安慰剂；97.5%置信区间：-9.4，2.3）的作用上不劣于安慰剂。在任何生物标志物方面，依托考昔与安慰剂、塞来昔布或布洛芬均无差异。结论：依托考昔在对所测量的CV风险标志物的作用方面与安慰剂、塞来昔布和布洛芬相当。
