Peptic ulcer and bleeding events associated with rofecoxib in a 3-year colorectal adenoma chemoprevention trial
Peptic ulcer and bleeding events associated with rofecoxib in a 3-year colorectal adenoma chemoprevention trial
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DOI：
10.1053/j.gastro.2006.11.012
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发表时间：
2007-02-01
期刊：
影响因子：
29.4
通讯作者：
Bresalier, Robert
中科院分区：
文献类型：
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作者：
Lanas, Angel;Baron, John A.;Bresalier, Robert
背景和目标：我们的目的是确定与使用标准临床剂量的选择性环氧合酶-2抑制剂相比，与使用安慰剂相关的症状性上消化道溃疡、溃疡穿孔、溃疡阻塞或出血发作（PUBS）的发生率。我们在此报告了一项为期3年、多中心、双盲、安慰剂对照试验中与使用罗非昔布25 mg相关的PUB结局，该试验旨在确定罗非昔布对结肠肿瘤性息肉复发风险的影响。方法：共有2587例有结直肠腺瘤病史的患者随机接受25 mg/天的罗非昔布或安慰剂治疗。由外部设盲委员会裁定制造商报告的PUBS。Kaplan-Meier和考克斯比例风险技术用于在意向治疗分析中估计PUB的发生率和相对风险。结果如下：接受罗非昔布治疗的患者比随机接受安慰剂治疗的患者有更高的PUB发生率（每100患者-年0.88 vs 0.18事件;相对危险度为4.9; 95%可信区间为1.98-14.54）。经证实的复杂PUB（溃疡穿孔、梗阻或出血）的发生率较低，但罗非昔布组在数值上高于安慰剂组（0.23 vs 0.06事件/100患者-年;相对风险为3.8; 95%置信区间为0.72 -37.46; P = 0.14）。在低剂量阿司匹林使用者和非使用者中，与安慰剂相比，罗非昔布增加了经证实的PUB的发生率。结论：在有结直肠腺瘤病史的患者中，与安慰剂相比，长期使用25 mg/天的罗非昔布与临床相关上消化道事件的风险增加相关。
Background & Aims: Our aim was to establish the incidence of symptomatic upper gastrointestinal ulcers, ulcer perforation, ulcer obstruction, or bleeding episodes (PUBS) associated with the use of selective cyclooxygenase-2 inhibitors at standard clinical doses compared with placebo. We report here on the PUB outcomes associated with the use of rofecoxib 25 mg in a 3-year, multicenter, double-blind, placebo-controlled trial designed to determine the effect of rofecoxib on the risk of recurrent neoplastic polyps of the colon. Methods: A total of 2587 patients with a history of colorectal adenomas underwent randomization to 25 mg/day of rofecoxib or to placebo. investigator-reported PUBS were adjudicated by an external blinded committee. Kaplan-Meier and Cox proportional hazards techniques were used to estimate incidence and relative risks of PUBs in an intention-to-treat analysis. Results: Patients assigned to rofecoxib had a higher incidence of confirmed PUBs than those randomized to placebo (.88 vs .18 events per 100 patient-years; relative risk, 4.9; 95% confidence interval, 1.98-14.54). The incidence of confirmed complicated PUBs (ulcer perforation, obstruction, or bleeds) was low, but was numerically higher in the rofecoxib than in the placebo group (.23 vs .06 events per 100 patient-years; relative risk, 3.8; 95% confidence interval, .72-37.46; P = .14). Rofecoxib increased the incidence of confirmed PUBs vs placebo in both low-dose aspirin users and nonusers. Conclusions: Among patients with a history of colorectal adenomas, the long-term use of 25 mg/day of rofecoxib was associated with an increased risk of clinically relevant upper gastrointestinal events when compared with placebo.