Bøtker H E, Sonne H S, Schmitz O, Nielsen T T
Department of Cardiology, Skejby Hospital, University Hospital in Aarhus, Denmark.
Am J Cardiol. 1998 Dec 1;82(11):1352-6. doi: 10.1016/s0002-9149(98)00640-7.
A significant proportion of patients with cardiac syndrome X have impaired coronary vasodilator capacity, which is thought to be caused by an increased sympathetic drive. The alpha1-adrenoceptor blocker, doxazosin, increases the coronary vasodilator reserve in patients with syndrome X. To study whether the augmentation is associated with clinical improvement in patients, we conducted a double-blind, placebo controlled, crossover study with doxazosin 1 to 4 mg once daily for 10 weeks in 16 patients with syndrome X (14 women and 2 men; mean +/- SD age 56+/-5 years). Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depression during bicycle exercise testing were compared after treatment with doxazosin 2 mg or placebo for 5 weeks and again after treatment with doxazosin 4 mg or placebo for 10 weeks. Insulin sensitivity was assessed by the minimal model after 10 weeks of doxazosin or placebo treatment. Twelve patients completed the protocol. Doxazosin 4 mg/day decreased systolic blood pressure at rest (109+/-16 vs 125+/-18 mm Hg, p <0.05) and increased basal heart rate (85+/-9 vs 76+/-11 beats/min, p <0.05), whereas hemodynamics were unaffected during exercise. Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depression were similar during treatment with doxazosin and placebo irrespective of the doxazosin dose. Insulin sensitivity was not different with doxazosin and placebo. In conclusion, alpha1 blockade does not significantly improve exercise duration, angina pectoris, and ST-segment depression despite a favorable vasodilator effect in patients with syndrome X. The absent clinical efficacy of doxazosin may challenge the use of the coronary vasodilator capacity as an appropriate method to subclassify patients with syndrome X.
相当一部分心脏综合征X患者存在冠状动脉扩张能力受损的情况，这被认为是由交感神经驱动增加所致。α1肾上腺素能受体阻滞剂多沙唑嗪可增加综合征X患者的冠状动脉扩张储备。为研究这种增加是否与患者的临床改善相关，我们进行了一项双盲、安慰剂对照、交叉研究，对16例综合征X患者（14例女性和2例男性；平均±标准差年龄56±5岁）每日一次给予1至4毫克多沙唑嗪，持续10周。在分别接受2毫克多沙唑嗪或安慰剂治疗5周后以及接受4毫克多沙唑嗪或安慰剂治疗10周后，比较自行车运动试验期间的心绞痛发作时间、运动持续时间、出现0.1毫伏ST段压低的时间以及最大ST段压低情况。在多沙唑嗪或安慰剂治疗10周后，通过最小模型评估胰岛素敏感性。12例患者完成了研究方案。每日4毫克多沙唑嗪可降低静息收缩压（109±16比125±18毫米汞柱，p<0.05）并增加基础心率（85±9比76±11次/分钟，p<0.05），而运动期间血流动力学未受影响。无论多沙唑嗪剂量如何，在多沙唑嗪和安慰剂治疗期间，心绞痛发作时间、运动持续时间、出现0.1毫伏ST段压低的时间以及最大ST段压低情况均相似。多沙唑嗪和安慰剂治疗后的胰岛素敏感性无差异。总之，尽管α1受体阻滞对综合征X患者有良好的血管扩张作用，但并未显著改善运动持续时间、心绞痛和ST段压低情况。多沙唑嗪缺乏临床疗效可能会对将冠状动脉扩张能力作为综合征X患者亚分类的合适方法提出挑战。
