Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery
Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery
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DOI：
10.1056/nejmoa050330
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发表时间：
2005-03-17
影响因子：
158.5
通讯作者：
Verburg, KM
中科院分区：
文献类型：
--
作者：
Nussmeier, NA;Whelton, AA;Verburg, KM
背景：伐地昔布及其静脉注射前体药物帕雷昔布用于治疗术后疼痛，但可能涉及冠状动脉旁路移植术(CABG)后的风险。我们进行了一项随机试验，以评估这些药物在冠状动脉搭桥术后的安全性。方法：在这项包括10天治疗和30天随访的随机双盲研究中，1671名患者被随机分配到接受静脉注射帕罗昔布至少3天，然后口服伐地昔布10天；静脉注射安慰剂后口服伐地昔布；或安慰剂10天。所有患者都可以获得标准的阿片类药物。主要终点是预先定义的不良事件的发生频率，包括心血管事件、肾功能衰竭或功能障碍、胃十二指肠溃疡和伤口愈合并发症。结果：与仅给予安慰剂的组相比，服用帕瑞昔布和伐地昔布的组以及给予安慰剂和伐地昔布的组至少有一项确认不良事件的患者比例更高(这两组中的每一组均为7.4%，而安慰剂组为4.0%；每次比较的风险比为1.9；95%的可信区间为1.1至3.2；与安慰剂组的每次比较P=0.02)。特别是，在服用帕瑞昔布和伐地昔布的患者中，心血管事件(包括心肌梗死、心脏骤停、中风和肺栓塞)比服用安慰剂的患者更常见(2.0%比0.5%；风险比3.7；95%可信区间1.0到13.5；P=0.03)。结论：冠脉搭桥术后使用帕瑞昔布和伐地昔布与心血管事件的发生率增加有关，这引起了人们对在这种情况下使用这些药物的严重关注。
BACKGROUND:Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG.METHODS:In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications.RESULTS:As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03).CONCLUSIONS:The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.