Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands.
JACC Cardiovasc Imaging. 2022 Aug;15(8):1473-1484. doi: 10.1016/j.jcmg.2022.03.012. Epub 2022 Apr 2.
Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of coronary vasomotor dysfunction (CVDys). However, studies substantiating its effect is this patient group are lacking.
The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on CVDys, as assessed by repeated coronary function testing (CFT), angina, and quality of life.
A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36).
In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36.
This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045).
地尔硫䓬在心绞痛和非阻塞性冠状动脉疾病（ANOCA）患者中被推荐并经常使用，这些患者疑似存在冠状动脉血管舒缩功能障碍（CVDys）。然而，在该患者群体中，缺乏证实其疗效的研究。
随机、安慰剂对照的 EDIT-CMD（地尔硫䓬改善冠状动脉微血管功能障碍的疗效：一项随机临床试验）评估了地尔硫䓬对通过重复冠状动脉功能测试（CFT）、心绞痛和生活质量评估的 CVDys 的影响。
共纳入 126 例 ANOCA 患者，并进行了 CFT。99 例患者确诊存在 CVDys，定义为存在血管痉挛（经冠状动脉内乙酰胆碱激发后）和/或微血管功能障碍（冠状动脉血流储备：<2.0，微血管阻力指数：≥25），其中 85 例患者被随机分配接受口服地尔硫䓬或安慰剂，剂量高达 360mg/d。6 周后进行第二次 CFT。主要终点是治疗成功的比例，定义为 CVDys 的 1 项异常参数正常化且无正常参数变为异常。次要终点是从基线到 6 周随访时血管痉挛、微血管阻力指数、冠状动脉血流储备、症状（西雅图心绞痛问卷）或生活质量（研究和开发问卷 36）的变化。
共有 73 例患者（38 例地尔硫䓬组和 35 例安慰剂组）接受了第二次 CFT。两组之间 CFT 的改善无差异（地尔硫䓬组与安慰剂组：21%与 29%；P=0.46）。然而，更多接受地尔硫䓬治疗的患者从心外膜痉挛进展为微血管痉挛或无痉挛（47%与 6%；P=0.006）。地尔硫䓬组和安慰剂组之间的微血管功能障碍、西雅图心绞痛问卷或研究和开发问卷 36 无显著差异。
在 ANOCA 患者中首次进行的随机、安慰剂对照试验表明，与安慰剂相比，6 周的地尔硫䓬治疗并未显著改善 CVDys、症状或生活质量，但地尔硫䓬治疗确实降低了心外膜痉挛的发生率。（地尔硫䓬改善冠状动脉微血管功能障碍的疗效：一项随机临床试验[EDIT-CMD]；NCT04777045）
