Related Experiment Video
Updated: Sep 25, 2025
Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders
Published on: February 3, 2021
Efficacy of Diltiazem to Improve Coronary Vasomotor Dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial
Tijn P J Jansen1, Regina E Konst1, Annemiek de Vos2
1Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Insights
Diltiazem did not improve coronary vasomotor dysfunction (CVDys) or symptoms in patients with angina and nonobstructive coronary artery disease (ANOCA). However, diltiazem therapy did reduce the prevalence of epicardial spasm.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Diltiazem is commonly prescribed for angina with nonobstructive coronary artery disease (ANOCA), often linked to coronary vasomotor dysfunction (CVDys).
- Evidence substantiating diltiazem's efficacy in ANOCA patients with CVDys is limited.
Purpose of the Study:
- To evaluate the effect of diltiazem on CVDys using coronary function testing (CFT).
- To assess changes in angina symptoms and quality of life in patients with ANOCA treated with diltiazem.
Main Methods:
- A randomized, placebo-controlled trial (EDIT-CMD) involving 126 ANOCA patients undergoing CFT.
- 99 patients with confirmed CVDys were randomized to diltiazem or placebo for 6 weeks, followed by repeat CFT.
Main Results:
- No significant difference in overall CFT improvement between diltiazem and placebo groups (21% vs 29%, P=0.46).
- Diltiazem significantly reduced epicardial spasm progression compared to placebo (47% vs 6%, P=0.006).
- No differences observed in microvascular dysfunction, angina symptoms, or quality of life.
Conclusions:
- Six weeks of diltiazem therapy did not substantially improve CVDys, symptoms, or quality of life in ANOCA patients.
- Diltiazem therapy was effective in reducing the prevalence of epicardial spasm in this patient group.
Background:
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.
Objectives:
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.
Methods:
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).
Results:
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.
Conclusions:
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).
Related Concept Videos
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
01:16Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
01:23Antihypertensive Drugs: Vasodilators
01:27Coronary Artery Disease V: Interprofessional Care
01:30Coronary Artery Disease III: Clinical Manifestations