對於膀胱過動症的藥物治療，抗膽鹼藥物是目前最常見的使用藥物，但其常有令病患困擾的副作用，包括口乾、便祕、甚至在老年族群可能發生認知障礙等情形，因此造成病患服藥順從性不高，以致膀胱過動症的治療效果不佳。Mirabegron是選擇性的β3腎上腺素受體促效劑(β3-adrenoreceptor agonist)，是用於治療膀胱過動症的新一代藥物，而日本是全世界第一個核准使用的國家，其於2011年開始使用，台灣則是在2014年開始引進並納入健保給付。對於膀胱過動症的治療，mirabegron與抗膽鹼藥物的療效相當，但其上述常見抗膽鹼藥物副作用的比例是較低的，因此病人的服藥順從性較高。然而，由於mirabegron是β3腎上腺素受體促效劑，儘管其受體選擇性高，但對於心血管的副作用以及併發症，包括心跳加速、血壓升高、心律變異、甚至是其他嚴重心臟疾患的發生，是臨床醫師在使用上觀察的重點，而使用在膀胱過動症同時合併有心血管疾患的病患上，其安全性更是臨床醫師所擔心的部分。因有此安全性顧慮，故此篇研究發表在2016年International Journal of Urology 期刊，報告mirabegron在日本上市後的藥品試驗安全性。

此研究是從一大型的藥品上市後研究報告所衍生的子研究報告，原報告是評估9795位膀胱過動症患者在經過mirabegron治療四周後的安全性，整體的副作用發生率是6.07%(Nozawa Y, et al. 2016 Low Urin Tract Symptoms)。此子研究報告收集了236位同時具有輕中度心血管疾病(即NYHA class I-II)的膀胱過動症患者，其中61.9%是男性，60.2%是年紀≥75歲，93.6%同時有合併心血管疾患(包括心律不整67.8%、以及心絞痛19.1%)。在此病患族群中，mirabegron的每日使用劑量25mg及50mg分別佔19.9%及80.1%。在藥物治療四周後，83.3%的病人在醫師評估下是有療效的，然而有5.51%病人產生心血管相關的副作用反應，其大部分都是輕度症狀，在停藥觀察後即改善，並無產生任何嚴重併發症情形。在治療後，病患平均心跳數顯著上升，但幅度僅每分增加1.24下，而在心電圖上的PR, QRS 或是QT interval皆無產生明顯延長或其他變化。治療後的心跳數增加與年紀、性別、治療前的心電圖參數、或是治療前的心跳數皆無顯著相關。

總結，根據此大型的日本上市後研究報告，使用mirabegron於膀胱過動症同時合併有輕中度心血管疾患的患者是有效且安全的，並不會產生嚴重的心血管併發症。因此，只要謹慎篩選病人，排除掉嚴重心血管疾患病患，臨床醫師是可以安心地使用mirabegron，提供膀胱過動症病人一長期有效的藥物治療選擇。

OBJECTIVES:
To assess the effect of 25 or 50 mg mirabegron on cardiovascular end-points and adverse drug reactions in real-world Japanese patients with overactive bladder and cardiovascular disease.

METHODS:
Participants had overactive bladder, a history of/coexisting cardiovascular disease and a 12-lead electrocardiogram carried out ≤7 days before initiating 4 weeks of mirabegron treatment. Patients with "serious cardiovascular disease" (class III or IV on the New York Heart Association functional classification and further confirmed by expert analysis) were excluded. Patient demographics, physical characteristics and cardiovascular history were recorded. After 4 weeks, patients underwent another electrocardiogram. Incidence of cardiovascular adverse drug reactions and change from baseline in electrocardiogram parameters (RR, PR, QRS intervals, Fridericia's corrected QT and heart rate) were assessed.

RESULTS:
Of 316 patients registered, 236 met criteria and had baseline/post-dose electrocardiograms: 61.9% male; 60.2% aged ≥75 years; 93.6% with coexisting cardiovascular disease, notably, arrhythmia (67.8%) and angina pectoris (19.1%). Starting mirabegron daily doses were 25 mg (19.9%) or 50 mg (80.1%). The incidence of cardiovascular adverse drug reactions was 5.51%. After 4 weeks, the mean heart rate increased by 1.24 b.p.m. (statistically significant, but clinically acceptable as per previous trials). No significant changes were observed in PR, QRS or Fridericia's corrected QT. No significant correlations in the total population or age-/sex-segregated subgroups were observed between baseline Fridericia's corrected QT and change at 4 weeks. No correlation for heart rate versus change from baseline heart rate with treatment was observed.

CONCLUSIONS:
Mirabegron was well tolerated in real-world Japanese patients with overactive bladder and coexisting cardiovascular disease. No unexpected cardiovascular safety concerns were observed.