Cardiovascular Safety of Tiotropium in Patients With COPD
Cardiovascular Safety of Tiotropium in Patients With COPD
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DOI：
10.1378/chest.09-0011
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发表时间：
2010-01-01
期刊：
影响因子：
9.6
通讯作者：
Tashkin, Donald P.
中科院分区：
文献类型：
--
作者：
Celli, Bartolome;Decramer, Marc;Tashkin, Donald P.
背景资料：通过在COPD患者中进行为期4年的试验，噻托溴铵的临床试验安全性数据库得到了扩充，这为更好地评估噻托溴铵的心血管（CV）特征提供了机会。方法：考虑符合以下标准的试验：>= 4周、随机、双盲、平行组、安慰剂对照。入选/排除标准相似，包括肺量测定证实的COPD，>= 10包年吸烟，年龄>= 40岁。使用标准化病例报告表在每次试验中收集不良事件。发生率（IR）由发生事件的患者总数除以总风险时间确定。计算噻托溴铵/安慰剂的率比（RR）和95% CI。确定全因死亡率和选定CV事件的IR，包括复合CV终点，包括CV死亡、非致死性心肌梗死（MI）、非致死性卒中以及术语猝死、心源性猝死和心源性death.Results：共有19，545例患者随机分组：来自30项试验的10，846例（噻托溴铵）和8，699例（安慰剂）。平均FEV 1 = 1.15 +/- 0.46 L（41 +/- 14%预测值），76%男性，平均年龄= 65 +/- 9岁。研究药物的累积暴露量分别为13，146（噻托溴铵）和11，095（安慰剂）患者-年。对于全因死亡率，IR为3.44（噻托溴铵）和4.10（安慰剂）/100患者-年（RR [95% CI] = 0.88 [0.77-0.999]）。CV终点的IR为2.15（噻托溴铵）和2.67（安慰剂）/100患者-年（RR [95% CI] = 0.83（0.71-0.98]）。不包括非致死性MI和卒中的CV死亡率的IR为0.91（噻托溴铵）和1.24（安慰剂）/100患者-年（RR [95% CI] = 0.77 [0.60-0.98]）。对于总MI、心力衰竭和卒中，RR（95%CI）分别为0.78（0.59-1.02）、0.82（0.69-0.98）和1.03（0.79-1.35）。结论：噻托溴铵与全因死亡率、CV死亡率和CV事件的风险降低相关。胸部2010; 137（1）：20-30
Background: The clinical trial safety database for tiotropium has been augmented with a 4-year trial in patients with COPD, which provides an opportunity to better evaluate the cardiovascular (CV) profile of tiotropium.Methods: Trials with the following criteria were considered: >= 4 weeks, randomized, double-blind, parallel-group, placebo-controlled. Inclusion/exclusion criteria were similar, including spirometry-confirmed COPD, >= 10 pack-year smoking, and age >= 40 years. Adverse events were collected throughout each trial using standardized case report forms. Incidence rates (IRs) were determined from the total number of patients with an event divided by total time at risk. Rate ratios (RRs) and 95% CI for tiotropium/placebo were calculated. IRs were determined for all-cause mortality and selected CV events, including a composite CV end point encompassing CV deaths, nonfatal myocardial infarction (MI), nonfatal stroke, and the terms sudden death, sudden cardiac death, and cardiac death.Results: There were 19,545 patients randomized: 10,846 (tiotropium) and 8,699 (placebo) from 30 trials. Mean FEV1 = 1.15 +/- 0.46 L (41 +/- 14% predicted), 76% men, mean age = 65 +/- 9 years. Cumulative exposure to study drug was 13,146 (tiotropium) and 11,095 (placebo) patient-years. For all-cause mortality, the IR was 3.44 (tiotropium) and 4.10 (placebo) per 100 patient-years (RR [95% CI] = 0.88 [0.77-0.999]). IR for the CV end point was 2.15 (tiotropium) and 2.67 (placebo) per 100 patient-years (RR [95% CI] = 0.83 (0.71-0.98]). The IR for the CV mortality excluding nonfatal MI and stroke was 0.91 (tiotropium) and 1.24 (placebo) per 100 patient-years (RR [95% CI] = 0.77 [0.60-0.98]). For total MI, cardiac failure, and stroke the RRs (95% CI) were 0.78 (0.59-1.02), 0.82 (0.69-0.98), and 1.03 (0.79-1.35), respectively.Conclusion: Tiotropium was associated with a reduction in the risk of all-cause mortality, CV mortality, and CV events. CHEST 2010; 137(1):20-30