长效β激动剂：哮喘临床试验中福莫特罗的安全性资料分析
2009/05/18
关键词：哮喘；福莫特罗；长效β2激动剂；发病率；死亡率；安全性
自从研究报告沙美特罗可能增加哮喘患者的呼吸相关性死亡后，长效β激动剂治疗的安全性受到质疑。为了检验福莫特罗的危险性，Sears等系统回顾研究了阿斯利康公司支持的有关福莫特罗治疗哮喘的随机、对照、平行试验。比照研究了福莫特罗对患者的危险性，包括需要关注的治疗次数、死亡率和严重不良事件（SAEs）等，尤其是哮喘相关性死亡。
资料分析表明，在49,906 例随机接受福莫特罗治疗的患者(92% 使用ICS)中有8例（每千人年0.34例）出现哮喘相关性死亡；而在18,098例不随机使用福莫特罗治疗患者(83%使用ICS)中有2例（每千人年0.22例）出现哮喘相关性死亡，两组比较无显著性差异。福莫特罗组的哮喘相关性SAEs的发病率(0.75%)明显低于非福莫特罗组（1.10%)，而且增加福莫特罗剂量也不增加哮喘相关性SAEs的发生率。福莫特罗组和非福莫特罗组患者心源性死亡或非心源性死亡的发生率均无显著性差异。而在起始就接受ICS治疗的患者中，46,003 随机接受福莫特罗治疗的患者中有7例出现哮喘相关性死亡(每千人年0.32例)，而在13,905不接受随机福莫特罗治疗的患者中有1例哮喘相关性死亡(每千人年0.14例)，两者比较也无统计学差异。
综合以上研究结果，福莫特罗并不增加心脏相关性严重不良事件，但也不减少哮喘相关性严重不良事件。
（韩伟 青岛市市立医院东院呼吸科 266071 摘译）
（Eur Respir J. 2009 Jan;33(1):21-32）
Eur Respir J. 2009 Jan;33(1):21-32.
Long-acting beta-agonists: a review of formoterol safety data from asthma clinical trials.
Sears MR, Ottosson A, Radner F, Suissa S.
Keywords: Asthma, formoterol, long-acting β-agonist, morbidity, mortality, safety
The safety of long-acting beta(2)-agonist (LABA) treatment in asthma has been questioned following reported increased respiratory deaths when salmeterol was added to usual pharmacotherapy. The aim of this study was to examine whether asthma, cardiac or all-cause mortality and morbidity were increased with formoterol use. The analysis included all AstraZeneca randomised controlled parallel-group asthma trials of 3-12-months duration involving formoterol. Risks associated with formoterol use compared with non-LABA treatment, overall and in combination with inhaled corticosteroids (ICS), were assessed using an intention-to-treat analysis of the rates and rate ratios of deaths and serious adverse events (SAEs). The main objective of this study was to compare asthma-related mortality in patients using formoterol and those not using formoterol. There were eight asthma-related deaths (0.34 per 1,000 person-yrs) among 49,906 formoterol-randomised patients (92% using ICS), and two (0.22 per 1,000 person-yrs) among 18,098 patients (83% using ICS) not randomised to formoterol, which was nonsignificant. Asthma-related SAEs (>90% of which were hospitalisations) were significantly fewer among formoterol-randomised patients (0.75 versus 1.10%). There was no increase in asthma-related SAEs with increased daily doses of formoterol (9, 18 or 36 microg). There was no significant difference in cardiac mortality or noncardiac nonasthma-related mortality in formoterol-randomised compared to non-LABA-treated patients. All-cause mortality was similar. In the data set in which all subjects were prescribed ICS at baseline, there were seven asthma-related deaths (0.32 per 1,000 person-yrs) among 46,003 formoterol-randomised patients and one (0.14 per 1,000 person-yrs) among 13,905 patients not randomised to formoterol, which was also nonsignificant. There were few asthma-related or cardiac-related deaths among patients randomised to formoterol, and all differences were nonsignificant compared with non-long-acting beta(2)-agonist-randomised patients. However, despite data on >68,000 patients, the power was insufficient to conclude that there was no increased mortality with formoterol. Cardiac-related serious adverse events were not increased, and asthma-related serious adverse events were significantly reduced with formoterol.
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艾美拉唑在未控制哮喘中的治疗作用
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固定剂量糖皮质激素和长效支气管扩张剂联合治疗作为哮喘患者初期维持治疗的效果
