内皮素-1受体拮抗剂马昔腾坦在心外膜和微血管痉挛中的疗效与安全性：一项概念验证研究。
Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study.
作者信息
Feenstra Rutger G T, Jansen Tijn P J, Matthijs Boekholdt S, Brouwer Janet E, Klees Margriet I, Appelman Yolande, Wittekoek Marianne E, van de Hoef Tim P, de Winter Robbert J, Piek Jan J, Damman Peter, Beijk Marcel A M
机构信息
Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
出版信息
Int J Cardiol Heart Vasc. 2023 Jul 16;47:101238. doi: 10.1016/j.ijcha.2023.101238. eCollection 2023 Aug.
BACKGROUND
Treatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment.
METHODS
Patients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase.
RESULTS
28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (durationseverity: -9 [-134 78] vs -45 [-353 11], p = 0.136 and frequencyseverity: -1.7 [-5.8 1.2] vs -1.8 [-6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo.
CONCLUSION
In patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.
背景
对于被诊断为因心外膜或微血管冠状动脉痉挛（CAS）所致心绞痛的患者，治疗颇具挑战性，因为尽管采用了传统药物治疗，患者往往仍有症状。在这项前瞻性、随机、双盲、安慰剂对照、序贯交叉概念验证研究中，我们比较了内皮素-1受体强效抑制剂马西替坦与安慰剂对接受背景药物治疗的有症状CAS患者的疗效和安全性。
方法
考虑纳入尽管接受了药物治疗但经侵入性痉挛激发试验诊断为CAS且每周心绞痛发作超过3次的患者。参与者作为附加治疗，每天接受10毫克马西替坦或安慰剂治疗28天。经过洗脱期后，患者交叉至另一治疗组。主要终点是心绞痛负荷的差异，计算方法为：[1]持续时间（分钟）×严重程度（采用视觉模拟量表（VAS）疼痛评分，范围1 - 10）；[2]用药期间心绞痛发作频率×严重程度，与导入期相比。
结果
28例患者完成了整个研究方案，其中22例为女性（79%），平均年龄55.3±7.6岁（心外膜CAS患者19例（68%），微血管CAS患者9例（32%））。与附加安慰剂治疗相比，附加马西替坦治疗期间心绞痛负荷的两个指标变化无差异（持续时间×严重程度：-9 [-134,78] 对比 -45 [-353,11]，p = 0.136；频率×严重程度：-1.7 [-5.8,1.2] 对比 -1.8 [-6.2,0.3]，p = 0.767）。在马西替坦治疗阶段和安慰剂治疗阶段，自我报告的不良事件的发生情况和性质非常相似。
结论
对于因心外膜或微血管CAS所致心绞痛且接受背景药物治疗的患者，与附加安慰剂治疗相比，每天10毫克马西替坦作为附加治疗28天并未减轻心绞痛负荷。试验注册https://trialsearch.who.int/，标识符：EUCTR2018 - 002623 - 42 - NL。注册日期：2019年2月20日。
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