Background: Long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are the mainstay of maintenance therapy for chronic obstructive pulmonary disease (COPD). Although previous studies have supported inhaled long-acting bronchodilators (ILABs) for overall cardiovascular safety, the risk of specific cardiovascular outcomes such as arrhythmia, heart failure and stroke is still unknown. Materials and methods: We systematically searched from PubMed, the Embase database and the Cochrane Library for published studies on ILABs and COPD, from its inception to November 10, 2018, with no language restrictions. The RRs and corresponding 95% CIs were pooled to evaluate ILAB/placebo. Results: Finally, 43 randomized controlled trials were included. Compared with placebo, ILABs do not increase the risk of overall and specific cardiovascular adverse events (AEs); on the contrary, they can reduce the incidence of hypertension (RR 0.73, 95% CI 0.55-0.98;I219.9%; P= 0.221). However, when stratified according to the specific agents of ILABs, olodaterol might reduce the risk of overall cardiovascular adverse events (OCAEs) (RR 0.65, 95% CI 0.49-0.88;I227.5%; P= 0.000), and the protective effect of lowing blood pressure disappeared. Similarly, the use of inhaled LABA might increase the risk of cardiac failure (RR 1.71, 95% CI 1.04-2.84;I20%; P= 0.538), but this risk disappeared when stratified according to the specific agents of LABA. Besides, formoterol might decrease the risk of cardiac ischemia (RR 0.53, 95% CI 0.32-0.91; I20%; P= 0.676). Conclusions: Overall, the use of ILABs was not associated with overall cardiovascular AEs in patients with stable COPD. When stratified according to the specific agents of LABA, olodaterol might reduce the risk of OCAE; and formoterol might decrease the risk of cardiac ischemia. LABA might reduce the incidence of hypertension, but might increase the risk of heart failure. Therefore, COPD patients with a history of heart failure should use it with caution.

译文

背景:长效毒蕈碱拮抗剂(LAMAs)和长效β2-激动剂(LABAs)是慢性阻塞性肺疾病(COPD)维持治疗的主要手段。尽管先前的研究已经支持吸入长效支气管扩张剂(ILABs)来提高整体心血管安全性,但尚不清楚具体的心血管结局(如心律不齐,心力衰竭和中风)的风险。资料和方法:我们从PubMed,Embase数据库和Cochrane图书馆系统地搜索了从成立到2018年11月10日的关于ILAB和COPD的已发表研究,没有语言限制。汇总RR和相应的95%CI,以评估ILA​​B /安慰剂。结果:最后,包括43个随机对照试验。与安慰剂相比,ILAB不会增加整体和特定心血管不良事件(AE)的风险;相反,它们可以降低高血压的发生率(RR 0.73,95%CI 0.55-0.98; I219.9%; P = 0.221)。但是,按照ILABs的特定药物进行分层时,奥洛他特罗可能会降低整体心血管不良事件(OCAE)的风险(RR 0.65,95%CI 0.49-0.88; I227.5%; P = 0.000),并具有保护作用血压降低消失了。同样,吸入LABA的使用可能会增加心力衰竭的风险(RR 1.71,95%CI 1.04-2.84; I20%; P = 0.538),但是根据LABA的特定药物分层后,这种风险消失了。此外,福莫特罗可能会降低心脏缺血的风险(RR 0.53,95%CI 0.32-0.91; I20%; P = 0.676)。结论:总的来说,在COPD稳定的患者中,使用ILABs与整体心血管AE无关。当按照LABA的具体药物进行分层时,奥洛他特罗可能会降低OCAE的风险。福莫特罗可能会降低心脏缺血的风险。 LABA可能会降低高血压的发生率,但可能会增加心力衰竭的风险。因此,有心力衰竭史的COPD患者应谨慎使用。

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