Anti-anginal Effect of Fasudil, a Rho-Kinase Inhibitor, in Patients With Stable Effort Angina: A Multicenter Study
Anti-anginal Effect of Fasudil, a Rho-Kinase Inhibitor, in Patients With Stable Effort Angina: A Multicenter Study
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Rho 激酶抑制剂 Fasudil 对稳定型心绞痛患者的抗心绞痛作用：一项多中心研究
DOI：
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发表时间：
2002
影响因子：
3
通讯作者：
Kazuzo Kato
中科院分区：
文献类型：
--
作者：
H. Shimokawa;K. Hiramori;H. Iinuma;S. Hosoda;H. Kishida;H. Osada;T. Katagiri;K. Yamauchi;Y. Yui;T. Minamino;M. Nakashima;Kazuzo Kato
Rho-激酶在血管平滑肌 (VSMC) 收缩的钙敏化中发挥重要作用，并且可能参与运动引起的心肌缺血期间不适当的冠状血管收缩。在这项多中心 II 期研究中，在稳定型劳力性心绞痛患者中检查了法舒地尔的抗心绞痛作用，法舒地尔口服后代谢为特定的 Rho 激酶抑制剂羟基法舒地尔。在 IIa 期试验中，经过 2 周的抗心绞痛药物清除期后，45 名患者接受了逐渐增加剂量的法舒地尔（每 2 周 5、10 和 20 mg TID）。法舒地尔治疗显着延长了最大运动时间和跑步机运动试验中 ST 段压低 1 mm 的时间（均 p < 0.01），而运动期间的血压和心率在治疗前后没有变化。随后以相同方式在 22 名患者中测试了更高剂量的法舒地尔（20 和 40 mg TID），并获得了相似的阳性结果。在IIb期试验中，经过2周的抗心绞痛药物洗脱期后，125名患者以双盲方式接受为期4周的不同剂量法舒地尔（5、10、20或40 mg TID）的口服治疗，并在治疗前后进行平板运动试验。同样，所有组中的最大运动时间和 ST 段压低 1 毫米的时间都延长了。各治疗组的运动耐量指数均存在显着的剂量反应关系，该指数由运动时间和 ST 段压低的综合效应决定（p = 0.006）。法舒地尔在两项试验中均具有良好的耐受性，没有任何严重的不良反应。这些结果表明法舒地尔（新型血管扩张剂中的第一种药物）用于治疗稳定型劳力性心绞痛的有效性和足够的安全性。
Rho-kinase plays an important role in calcium sensitization for vascular smooth muscle (VSMC) contraction and may be involved in the inappropriate coronary vasoconstriction during exercise-induced myocardial ischemia. In this multicenter phase II study, the anti-anginal effect of fasudil, which is metabolized to a specific Rho-kinase inhibitor hydroxyfasudil after oral administration, was examined in patients with stable effort angina. In the phase IIa trial, after a 2-week washout period of anti-anginal drugs, 45 patients received increasing doses of fasudil (5, 10, and 20 mg TID for every 2 weeks). The fasudil treatment significantly prolonged the maximum exercise time and the time to the onset of 1-mm ST segment depression on treadmill exercise test (both p < 0.01), whereas blood pressure and heart rate during exercise were unchanged before and after the treatment. Higher doses of fasudil (20 and 40 mg TID) were subsequently tested in 22 patients in the same manner with similar positive results. In the phase IIb trial, after a 2-week washout period of anti-anginal drugs, 125 patients were assigned, in a double-blind manner, to a 4-week oral treatment with a different dose of fasudil (5, 10, 20, or 40 mg TID) and treadmill exercise test was performed before and after the treatment. Again, both maximum exercise time and time to the onset of 1-mm ST segment depression were prolonged in all groups. A significant dose-response relation was noted across the treatment groups for the exercise tolerance index that was determined by the combined effect of exercise time and ST segment depression (p = 0.006). Fasudil was well tolerated in both trials without any serious adverse reactions. These results suggest the efficacy and adequate safety profile of fasudil, the first drug in a novel class of vasodilators, for the treatment of stable effort angina.
影响因子：
18.2
作者：
Kamm,KE;Stull,JT
通讯作者：
Stull,JT