Diltiazem did not improve coronary vasomotor dysfunction (CVDys) versus placebo for angina and no obstructive coronary artery disease (ANOCA) patients treated for 6 weeks, despite frequently being recommended for these patients. These were the findings of EDIT-CMD – the first randomized clinical trial in this population – presented Saturday at the American College of Cardiology’s 71st Annual Scientific Session in Washington, D.C., by lead author Tijn P.J. Jansen, MD, Radboud University Medical Center, the Netherlands. The results were published simultaneously online in JACC Cardiovascular Imaging. Despite a lack of well-powered, modern, randomized studies to support the effectiveness of the calcium channel blocker diltiazem in ANOCA patients suspected of CVDys, the drug is recommended and frequently prescribed in the population, the authors noted. CVDys is the underlying pathology in around 60% to 90% of ANOCA patients, they added. In turn, ANOCA patients make up a large proportion (up to 40%) of patients undergoing coronary angiography (CAG) for stable angina. In CVDys, ischemia is caused by vascular vasospasm and/or coronary microvascular dysfunction (CMD), “comprising impairment of vasodilation and increased microvascular resistance,” the authors reported in their manuscript. Patients with CVDys have worse cardiovascular prognoses and often have continuing episodes of chest pain leading to frequent emergency room and hospital visits, associated with raised healthcare costs, the researchers said. “Therefore, proper diagnosis and adequate treatment are of paramount importance,” the authors wrote. The current study was, therefore, established to assess the effects of diltiazem for these patients through repeat coronary function testing (CFT) – the gold standard to diagnose CVDys – as well as to evaluate the effects on angina symptoms and quality of life. A total 126 ANOCA patients were included and underwent CFT, and CVDys – defined as the presence of vasospasm after intracoronary acetylcholine provocation, and/or microvascular dysfunction – was confirmed in 99 patients. Those included were over 18 years of age, experienced chronic angina symptoms twice or more per week, had been classed as having ANOCA for less than 5 years, and had not used calcium channel blockers within the past 2 weeks. Those unable to undergo CFT were excluded, as were those contraindicated for calcium channel blockers. At baseline in both the placebo and treatment arms, patients’ mean age was 58 years, the majority were female (36% male in placebo vs. 31% male on diltiazem), while 23% and 22%, respectively, had a history of percutaneous coronary intervention, Jansen noted in his slides. In placebo, 52% had an angina score of III or IV under the Canadian Cardiovascular Society (CCS) classification at baseline vs. 44% on diltiazem, 89% on placebo and 85% on diltiazem had angina symptoms at rest and 77% vs. 76%, respectively, had angina symptoms during exercise, he added. Of the 99 patients, 85 were randomized to receive up to 360 mg/day of either oral diltiazem or placebo for 6 weeks, after which a second CFT was performed in 73 of the patients (38 on diltiazem and 35 on placebo). The researchers found that CFT improvement did not differ between the two groups, with diltiazem improving by 21% and placebo 29% (p = 0.46). However, more patients on diltiazem did progress from epicardial spasm to microvascular or no spasm (47% vs. 6%; p = 0.006). Nevertheless, no significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, symptom assessment questionnaire, or RAND-36 quality of life scoring. “This study underlines the paucity and thus necessity of large randomized clinical placebo-controlled trials in this rather underexplored patient population in order to acquire evidence based and patient-tailored treatment,” the researchers said. They called for larger clinical trials to further explore the effect of calcium channel blockers on specific endotypes of CVDys, symptoms, quality of life and prognosis.