Hanrahan John P, Grogan Donna R, Baumgartner Rudolf A, Wilson Amy, Cheng Hailong, Zimetbaum Peter J, Morganroth Joel
From Sepracor Inc. (JPH, DRG, RAB, AW, HC), Marlborough, Massachusetts; Beth Israel Deaconess Medical Center (PJZ), Harvard Medical School, Boston, Massachusetts; University of Pennsylvania School of Medicine (JM) and eResearch Technology, Inc. (JM), Philadelphia, Pennsylvania.
Medicine (Baltimore). 2008 Nov;87(6):319-328. doi: 10.1097/MD.0b013e31818fcc02.
Beta-adrenergic stimulation may increase heart rate and the potential for cardiac arrhythmias. The effect of inhaled long-acting beta2-agonists (LABAs) on these outcomes was evaluated in patients with chronic obstructive pulmonary disease (COPD) in 2 double-blind randomized clinical trials. The pretreatment arrhythmia occurrence frequency in these patients was also described. In this analysis, 24-hour Holter monitoring data were pooled from 2 identically designed Phase III trials. Patients were randomized to LABA treatment or placebo for 12 weeks: a) nebulized arformoterol 15 microg BID, b) 25 microg BID, or c) 50 microg QD; d) salmeterol metered dose inhaler 42 microg BID; or e) placebo. The 24-hour Holter monitoring was performed pretreatment and at Weeks 0 (first day of dosing), 6, and 12. We assessed the proportion of patients with each of 4 arrhythmias: atrial tachycardia, atrial fibrillation/flutter, and "nonsustained"; (4-10 beats) and "sustained"; (>10 beats) ventricular tachycardia. There were 5226 Holter recordings in 1429 treated patients. At baseline, there was a low frequency of occurrence of atrial fibrillation/flutter (0.1%), nonsustained ventricular tachycardia (3.1%), and >10 beat ventricular tachycardia (0.3%). Atrial tachycardia occurred frequently (41.8%). The proportion of patients with treatment-emergent atrial tachycardia ranged from 27% to 32% and was non-significantly higher, by approximately 2%-5% (p = 0.70), in the LABA groups compared with the placebo group. The rates of the other more serious arrhythmias did not increase with LABA treatment and were similar to placebo. All treatment groups (LABA and placebo) had consistent small decreases from baseline in mean 24-hour and maximum hourly heart rate. In conclusion, in this large cohort of COPD patients with no or stable cardiac comorbidities, a high proportion ( approximately 40%) of patients were observed to have atrial tachycardia before treatment, which increased by 2%-5% with LABA treatment. More serious arrhythmias were infrequent and did not increase with inhaled LABA therapy. LABA administration did not increase mean heart rate.
β-肾上腺素能刺激可能会增加心率以及发生心律失常的可能性。在两项双盲随机临床试验中，对慢性阻塞性肺疾病（COPD）患者吸入长效β2受体激动剂（LABA）对这些结果的影响进行了评估。还描述了这些患者治疗前心律失常的发生频率。在该分析中，汇总了两项设计相同的III期试验的24小时动态心电图监测数据。患者被随机分配接受LABA治疗或安慰剂治疗12周：a）雾化吸入阿福特罗15微克，每日两次；b）25微克，每日两次；或c）50微克，每日一次；d）沙美特罗定量气雾剂42微克，每日两次；或e）安慰剂。在治疗前以及第0周（给药第一天）、第6周和第12周进行24小时动态心电图监测。我们评估了出现以下4种心律失常的患者比例：房性心动过速、心房颤动/扑动，以及“非持续性”（4 - 10次心跳）和“持续性”（>10次心跳）室性心动过速。1429例接受治疗的患者中有5226份动态心电图记录。在基线时，心房颤动/扑动的发生率较低（0.1%），非持续性室性心动过速的发生率为（3.1%），>10次心跳的室性心动过速发生率为（0.3%）。房性心动过速发生率较高（41.8%）。出现治疗引发房性心动过速的患者比例在27%至32%之间，与安慰剂组相比，LABA组的该比例非显著升高，约高2% - 5%（p = 0.70）。其他更严重心律失常的发生率并未因LABA治疗而增加，且与安慰剂相似。所有治疗组（LABA组和安慰剂组）的24小时平均心率和每小时最高心率较基线均有一致的小幅下降。总之，在这一大群无心脏合并症或心脏合并症稳定 的COPD患者中，观察到治疗前有高比例（约40%）的患者存在房性心动过速，LABA治疗后增加了2% - 5%。更严重的心律失常并不常见，吸入LABA治疗后也未增加。LABA给药并未增加平均心率。
