在心绞痛和非阻塞性冠状动脉疾病(ANOCA)患者中推荐使用地尔硫,怀疑冠状动脉血管舒缩功能障碍(CVDys)。然而,证实其效果的研究是该患者组缺乏。
随机化,安慰剂对照EDIT-CMD(地尔硫改善冠状动脉微血管功能障碍的功效:一项随机临床试验)评估了地尔硫对CVDys,通过重复冠状动脉功能测试(CFT)评估,心绞痛,和生活质量。
共纳入126例ANOCA患者并接受CFT。CVDys,定义为存在血管痉挛(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),在99名患者中得到证实,其中85人随机接受口服地尔硫卓或安慰剂,最高剂量为360mg/d。6周后,进行了第二次CFT。主要终点是成功治疗的患者比例,定义为CVDys的1个异常参数的归一化,没有正常参数变得异常。次要终点是血管痉挛从基线到6周随访的变化,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(研究与发展问卷36)。
总共,73例患者(38例地尔硫卓与35例安慰剂)接受了第二次CFT。两组之间CFT的改善没有差异(地尔硫卓与安慰剂:21%对29%;P=0.46)。然而,更多接受地尔硫卓治疗的患者从心外膜痉挛发展为微血管痉挛或无痉挛(47%vs6%;P=0.006).地尔硫和安慰剂组在微血管功能障碍方面没有观察到显著差异,西雅图心绞痛问卷,或研究与发展问卷36。
这是第一次随机进行,在ANOCA患者中的安慰剂对照试验表明,使用地尔硫治疗6周,与安慰剂相比,没有实质性改善CVDys,症状,或生活质量,但是地尔硫卓治疗确实降低了心外膜痉挛的患病率。(地尔硫改善冠状动脉微血管功能障碍的功效:一项随机临床试验[EDIT-CMD];NCT04777045)。
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).