Tiotropium Respimat Inhaler and the Risk of Death in COPD
Tiotropium Respimat Inhaler and the Risk of Death in COPD
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DOI：
10.1056/nejmoa1303342
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发表时间：
2013-10-17
影响因子：
158.5
通讯作者：
Calverley, Peter
中科院分区：
文献类型：
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作者：
Wise, Robert A.;Anzueto, Antonio;Calverley, Peter
背景：在涉及慢性阻塞性肺疾病（COPD）患者的安慰剂对照试验中，使用Respimat吸入器给药5 g噻托溴铵的疗效与使用HandiHaler吸入器给药18 g噻托溴铵的疗效相似。虽然tiotropium HandiHaler与死亡率降低相关，但与安慰剂相比，tiotropium Respimat的死亡报告多于安慰剂。方法：在这项随机、双盲、平行组试验中，我们评估了每日一次剂量为2.5 g或5 g的噻托溴铵呼吸剂与每日一次剂量为18 g的噻托溴铵汉迪哈勒的安全性和有效性。主要终点是死亡风险（非劣效性研究，Respimat剂量为5 g或2.5 g vs. HandiHaler）和首次COPD加重风险（优势研究，Respimat剂量为5 g vs. HandiHaler）。我们还评估了心血管安全性，包括稳定性心脏病患者的安全性。ResultsDuring平均2.3年的随访中,Respimat HandiHaler是一系列关于死亡的风险(Respimat 5 g的剂量与HandiHaler:风险比,0.96;95%可信区间(CI), 0.84到1.09;Respimat 2.5 g的剂量与HandiHaler:风险比,1.00;95%可信区间,0.87至1.14),而不是优于HandiHaler对第一恶化的风险(Respimat 5 g的剂量与HandiHaler:风险比,0.98;95%可信区间,0.93 - 1.03)。三组患者的死亡原因和主要心血管不良事件发生率相似。结论5 g或2.5 g噻托溴铵对慢性阻塞性肺病患者的安全性和加重疗效与18 g噻托溴铵相似。（由勃林格殷格翰公司资助；TIOSPIR ClinicalTrials.gov编号：NCT01126437）
BackgroundTiotropium delivered at a dose of 5 g with the Respimat inhaler showed efficacy similar to that of 18 g of tiotropium delivered with the HandiHaler inhalation device in placebo-controlled trials involving patients with chronic obstructive pulmonary disease (COPD). Although tiotropium HandiHaler was associated with reduced mortality, as compared with placebo, more deaths were reported with tiotropium Respimat than with placebo.MethodsIn this randomized, double-blind, parallel-group trial involving 17,135 patients with COPD, we evaluated the safety and efficacy of tiotropium Respimat at a once-daily dose of 2.5 g or 5 g, as compared with tiotropium HandiHaler at a once-daily dose of 18 g. Primary end points were the risk of death (noninferiority study, Respimat at a dose of 5 g or 2.5 g vs. HandiHaler) and the risk of the first COPD exacerbation (superiority study, Respimat at a dose of 5 g vs. HandiHaler). We also assessed cardiovascular safety, including safety in patients with stable cardiac disease.ResultsDuring a mean follow-up of 2.3 years, Respimat was noninferior to HandiHaler with respect to the risk of death (Respimat at a dose of 5 g vs. HandiHaler: hazard ratio, 0.96; 95% confidence interval [CI], 0.84 to 1.09; Respimat at a dose of 2.5 g vs. HandiHaler: hazard ratio, 1.00; 95% CI, 0.87 to 1.14) and not superior to HandiHaler with respect to the risk of the first exacerbation (Respimat at a dose of 5 g vs. HandiHaler: hazard ratio, 0.98; 95% CI, 0.93 to 1.03). Causes of death and incidences of major cardiovascular adverse events were similar in the three groups.ConclusionsTiotropium Respimat at a dose of 5 g or 2.5 g had a safety profile and exacerbation efficacy similar to those of tiotropium HandiHaler at a dose of 18 g in patients with COPD. (Funded by Boehringer Ingelheim; TIOSPIR ClinicalTrials.gov number, NCT01126437.)