Conti C R, Hill J A, Feldman R L, Conti J B, Pepine C J
Am Heart J. 1985 Jul;110(1 Pt 2):251-6. doi: 10.1016/0002-8703(85)90495-8.
The efficacy of isosorbide dinitrate (ISDN) in variant angina is enhanced by the addition of a calcium antagonist. A prospective double-blind, crossover trial of ISDN, 40 to 120 mg/day, and nifedipine, 40 to 120 mg/day, in 19 patients with variant angina and various degrees of coronary atherosclerosis showed that although both agents were equally effective in controlling angina of vasospastic origin, some patients responded better to one or the other drug. Such response could not be predicted by demographic factors, ECG changes, or degree of coronary atherosclerosis. Since quantitative angiography done in a similar group of patients showed that intracoronary nitroglycerin, 200 micrograms, was a more potent vasodilator than sublingual nifedipine, 10 mg (p less than 0.01), the calcium antagonists may have a different mechanism of preventing variant angina attacks and may act in an additive or synergistic fashion when administered in combination with long-acting nitrates. Such a combination will increase coronary blood flow, reduce ventricular volume and end-diastolic pressure, and reduce systemic arterial resistance. Coronary vasospasm may be directly prevented by a general inhibition of smooth muscle contraction by the calcium antagonist. Clinical studies suggest that combination therapy significantly improves the long-term prognosis of patients with variant angina and reduces the need for bypass surgery. Thus combining ISDN with a calcium antagonist is a rational and effective treatment for variant angina.
联用钙拮抗剂可增强硝酸异山梨酯(ISDN)治疗变异型心绞痛的疗效。一项针对19例患有变异型心绞痛且伴有不同程度冠状动脉粥样硬化的患者进行的前瞻性双盲交叉试验,分别给予ISDN每日40至120毫克以及硝苯地平每日40至120毫克,结果显示,尽管两种药物在控制血管痉挛性心绞痛方面同样有效,但部分患者对其中一种药物的反应更佳。此类反应无法通过人口统计学因素、心电图变化或冠状动脉粥样硬化程度来预测。鉴于在一组类似患者中进行的定量血管造影显示,200微克冠状动脉内硝酸甘油比10毫克舌下含服硝苯地平是更强效的血管扩张剂(P<0.01),钙拮抗剂预防变异型心绞痛发作的机制可能不同,并且与长效硝酸盐联合使用时可能具有相加或协同作用。这种联合用药将增加冠状动脉血流量,减少心室容积和舒张末期压力,并降低体循环动脉阻力。钙拮抗剂可通过全面抑制平滑肌收缩直接预防冠状动脉痉挛。临床研究表明,联合治疗可显著改善变异型心绞痛患者的长期预后,并减少搭桥手术的需求。因此,将ISDN与钙拮抗剂联合使用是治疗变异型心绞痛的合理且有效的方法。