尽管有充分的证据支持β2-激动剂在哮喘和慢性阻塞性肺疾病(COPD)中的疗效,心脏中β1-和β2-肾上腺素受体的出现提示β2-激动剂可能具有有害的心脏效应.我们调查了长效或短效β2激动剂(LABA或SABA)或ICS(吸入性皮质类固醇)/LABA的新使用者与主要不良心血管事件(MACE)之间的关联。
使用英国临床实践研究数据链对哮喘患者进行巢式病例对照分析,COPD或哮喘-COPD与LABA的初始治疗重叠,SABA,ICS/LABA,ICS,1998年1月1日至2018年7月31日期间的长效或短效毒蕈碱拮抗剂(LAMA或SAMA)。主要结果是MACE,定义为中风的第一次出现,心力衰竭,心肌梗塞,心律失常,或心血管死亡。每个病例都与多达10个年龄对照相匹配,性别,队列进入的日期,和随访时间。在控制潜在的混杂因素后,使用条件逻辑回归估计与β2激动剂相关的MACE风险。
该队列包括180,567个新的β2-激动剂用户,ICS,SAMA,或者LAMA.在哮喘患者中,β2-激动剂与MACE的风险无关(SABA与ICS:HR1.29[0.96-1.73];ICS/LABA与ICS,HR0.75[0.33-1.73])。相比之下,在COPD患者中,LABA(HR,2.38[1.04-5.47]),SABA(HR,2.02[1.13-3.59])和ICS/LABA(HR,2.08[1.04-4.16])用户与SAMA用户相比,MACE的风险增加。在哮喘-COPD重叠患者中,SABA(HR,与ICS相比,2.57[1.26-5.24])与MACE风险增加相关。
总之,引发LABA,SABA,COPD中的ICS/LABA或哮喘-COPD中的SABA重叠与MACE风险增加相关。哮喘患者之间未观察到相关性。
Despite ample evidence underpinning the efficacy of β2-agonists in asthma and chronic obstructive pulmonary disease (COPD), the occurrence of β1- and β2-adrenoceptors in the heart suggests that β2-agonists may have deleterious cardiac effects. We investigated the association between new users of long-or short-acting β2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA and major adverse cardiovascular events (MACE).
A nested
case-control analysis was conducted using the UK Clinical Practice Research Datalink of patients with asthma, COPD or asthma-COPD overlap with initial treatment of LABA, SABA, ICS/LABA, ICS, long-or short-acting muscarinic antagonist (LAMA or SAMA) between 01 January 1998 and 31 July 2018. The primary outcome was MACE, defined as the first occurrence of stroke, heart failure, myocardial infarction, arrhythmia, or cardiovascular death. Each
case was matched with up to 10 controls on age, sex, date of cohort-entry, and duration of follow-up. The risk of MACE associated with β2-agonists was estimated using conditional logistic regression after controlling for potential confounders.
The cohort included 180,567 new users of β2-agonists, ICS, SAMA, or LAMA. Among asthmatics, β2-agonists were not associated with the risk of MACE (SABA vs ICS: HR 1.29 [0.96-1.73]; ICS/LABA vs ICS, HR 0.75 [0.33-1.73]). In contrast, among COPD patients, LABA (HR, 2.38 [1.04-5.47]), SABA (HR, 2.02 [1.13-3.59]) and ICS/LABA (HR, 2.08 [1.04-4.16]) users had an increased risk of MACE compared with SAMA users. Among patients with asthma-COPD overlap, SABA (HR, 2.57 [1.26-5.24]) was associated with an increased risk of MACE compared with ICS.
In conclusion, initiation of LABA, SABA, or ICS/LABA in COPD or SABA in asthma-COPD overlap is associated with increased risk of MACE. No associations were observed among patients with asthma.