Cannon R O, Brush J E, Schenke W H, Tracy C M, Epstein S E
Cardiovascular Diagnosis Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Cardiol. 1990 Jul 1;66(1):37-41. doi: 10.1016/0002-9149(90)90732-g.
Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/- 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST-segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking lidoflazine. Repeat invasive study of coronary flow in 11 patients taking lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias.
利多氟嗪是一种哌嗪衍生物钙拮抗剂，对22例微血管性心绞痛患者（胸痛、冠状动脉造影和左心室正常、服用麦角新碱后起搏时微血管收缩反应以及服用双嘧达莫后冠状动脉血流反应受限）进行了治疗研究。22例患者中有18例报告在每日服用360毫克利多氟嗪时症状有所改善。与基线运动平板试验相比，利多氟嗪使运动持续时间显著改善（812±337秒对628±357秒，p<0.01），胸痛发作时间显著延长（530±343秒对348±246秒，p<0.01）。在基线测试期间有缺血性ST段改变的5例患者在服用利多氟嗪时，ST段压低延迟了近4分钟（3例患者）或无ST段压低（2例患者）。对11例服用利多氟嗪的患者进行冠状动脉血流的重复有创研究表明，与最初的无药研究相比，在静息、起搏、服用麦角新碱后起搏以及服用双嘧达莫后，冠状动脉血管舒张显著增强（所有p<0.03）。在为期7周治疗期的随机、安慰剂对照研究阶段，完成该阶段研究的11例患者中有9例更喜欢利多氟嗪，与安慰剂相比，所有患者服用利多氟嗪后运动能力均有所改善。然而，3例患者出现恶性室性心律失常，1例患者在服用利多氟嗪时死亡，导致研究终止。微血管性心绞痛中有限的冠状动脉血管舒张反应有一个可逆的血管收缩成分，可能是由于收缩期钙水平升高所致。尽管利多氟嗪在血液动力学、症状和运动方面有有益作用，但由于其有导致潜在致命性室性心律失常的倾向，临床使用可能不安全。
