Cazzola M, Imperatore F, Salzillo A, Di Perna F, Calderaro F, Imperatore A, Matera M G
Divisione di Pneumologia e Allergologia and the Settore di Farmacologia Clinica Respiratoria, Ospedale A. Cardarelli, Napoli, Italy.
Chest. 1998 Aug;114(2):411-5. doi: 10.1378/chest.114.2.411.
There are several reports of documented adverse cardiac effects during treatment with beta-agonists. Since one should be aware that this may be a problem in patients with preexisting cardiac disorders, we have conducted a randomized, single-blind, balanced, crossover, placebo-controlled study to assess the cardiac effects of two single doses of formoterol (12 microg and 24 microg) and one single dose of salmeterol (50 microg) in 12 patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia (PaO2<60 mm Hg).
Each patient was evaluated at a screening visit that included spirometry, blood gas analysis, plasma potassium measurement, and 12-lead ECG. In following nonconsecutive days, all patients underwent Holter monitoring 24 h during each of the four treatments. Holter monitoring was started soon before drug administration in the morning. Plasma potassium level was measured before drug inhalation, at 2-h intervals for 6 h, and at 9, 12, and 24 h following administration. None of our patients took rescue medication during the 24-h period.
Holter monitoring showed a heart rate higher after formoterol, 24 microg, than after formoterol, 12 microg, and salmeterol, 50 microg, and supraventricular or ventricular premature beats more often after formoterol, 24 microg. Formoterol, 24 microg, significantly reduced plasma potassium level for 9 h when compared with placebo, whereas formoterol, 12 microg, was different after 2 h and salmeterol, 50 microg, from 4 to 6 h.
The results of this study suggest that if a COPD patient is suffering from preexisting cardiac arrhythmias and hypoxemia, long-acting beta-agonists may have adverse effects on the myocardium, although the recommended single dose of salmeterol and formoterol, 12 microg, allows a higher safety margin than formoterol, 24 microg.
有几份报告记录了使用β受体激动剂治疗期间出现的不良心脏效应。由于人们应该意识到这在已有心脏疾病的患者中可能是个问题，我们开展了一项随机、单盲、均衡、交叉、安慰剂对照研究，以评估两剂单剂量福莫特罗（12微克和24微克）和一剂单剂量沙美特罗（50微克）对12例患有慢性阻塞性肺疾病（COPD）且已有心律失常和低氧血症（动脉血氧分压<60毫米汞柱）患者的心脏效应。
在筛选访视时对每位患者进行评估，包括肺活量测定、血气分析、血浆钾测量和12导联心电图检查。在随后不连续的几天里，所有患者在四种治疗的每一种期间均接受24小时动态心电图监测。动态心电图监测在早晨给药前不久开始。在药物吸入前、给药后6小时内每2小时以及给药后9、12和24小时测量血浆钾水平。我们的患者在24小时期间均未服用急救药物。
动态心电图监测显示，24微克福莫特罗给药后的心率高于12微克福莫特罗和50微克沙美特罗给药后，且24微克福莫特罗给药后室上性或室性早搏更频繁。与安慰剂相比，24微克福莫特罗可使血浆钾水平在9小时内显著降低，而12微克福莫特罗在2小时后以及50微克沙美特罗在4至6小时后与安慰剂有差异。
本研究结果表明，如果COPD患者已有心律失常和低氧血症，长效β受体激动剂可能对心肌有不良影响，尽管推荐的单剂量沙美特罗和12微克福莫特罗比24微克福莫特罗有更高的安全边际。
