Celecoxib for the prevention of sporadic colorectal adenomas
Celecoxib for the prevention of sporadic colorectal adenomas
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DOI：
10.1056/nejmoa061355
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发表时间：
2006-08-31
影响因子：
158.5
通讯作者：
Hawk, Ernest T.
中科院分区：
文献类型：
--
作者：
Bertagnolli, Monica M.;Eagle, Craig J.;Hawk, Ernest T.
背景：研究表明，抑制环氧化酶 - 2（COX - 2）的药物可减少动物以及家族性腺瘤性息肉病患者的结直肠腺瘤数量，这提示COX - 2抑制剂可能也能预防散发性结直肠肿瘤。
方法：我们将在研究入组前已切除腺瘤的患者随机分组，分别接受安慰剂（679例患者），或每日两次服用200毫克（685例患者）或400毫克（671例患者）的塞来昔布。随机分组根据低剂量阿司匹林的使用情况进行分层。在随机分组后的1年和3年进行结肠镜随访检查。采用Mantel - Haenszel检验的寿命表扩展法比较各组新发现的结直肠腺瘤的发生情况。
结果：89.5%的随机分组患者在第1年完成了结肠镜随访检查，75.7%的患者在第3年完成。到第3年时，估计安慰剂组患者检测到1个或多个腺瘤的累积发生率为60.7%，而每日两次服用200毫克塞来昔布的患者为43.2%（风险比为0.67；95%置信区间为0.59 - 0.77；P < 0.001），每日两次服用400毫克塞来昔布的患者为37.5%（风险比为0.55；95%置信区间为0.48 - 0.64；P < 0.001）。安慰剂组18.8%的患者发生严重不良事件，低剂量塞来昔布组为20.4%（风险比为1.1；95%置信区间为0.9 - 1.3；P = 0.5），高剂量组为23.0%（风险比为1.2；95%置信区间为1.0 - 1.5；P = 0.06）。与安慰剂相比，塞来昔布与心血管事件风险增加相关（低剂量组风险比为2.6；95%置信区间为1.1 - 6.1；高剂量组风险比为3.4；95%置信区间为1.5 - 7.9）。
结论：这些研究结果表明塞来昔布是一种预防结直肠腺瘤的有效药物，但由于潜在的心血管事件，不能常规推荐用于该适应证。
Background: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia.Methods: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test.Results: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P < 0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P < 0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9).Conclusions: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication.