Randomized controlled trial of vericiguat in patients with coronary microvascular dysfunction causing stable chest pain (V-COM): study protocol for a randomized control trial.

BACKGROUND: Previous studies have shown that ∼50% of patients with stable chest pain have no obstructive coronary artery disease (CAD), yet remain at higher risk of major adverse cardiovascular events (MACE) compared to patients without chest pain. Coronary microvascular dysfunction (CMD) is a major cause of ischemia with no obstructive coronary arteries (INOCA). While therapies for CMD are lacking, Vericiguat, a soluble guanylate cyclase stimulator, has shown improvement in coronary microvascular circulation in animal studies. Quantitative stress cardiovascular magnetic resonance (CMR) allows the quantification of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). This study aims to conduct a randomized controlled trial to determine if Vericiguat improves MBF and MPR in patients with stable chest pain and INOCA caused by CMD.

METHODS/DESIGN: V-COM is a single-blind, randomized controlled trial. Ninety-four patients aged 40-80 years with recurrent stable chest pain, nonobstructive coronary arteries on recent coronary computed tomography (CT) or invasive angiography, and CMD defined by stress CMR (MPR <2.19 or stress MBF <2.19 mL/g/min) will be recruited across six centers in Hong Kong. Participants will be randomized 1:1 to vericiguat plus optimal medical therapy (intervention) or optimal medical therapy alone (control). Vericiguat will be prescribed once daily for 6 months, starting at 2.5 mg and titrated up to a target dose of 10 mg based on systolic blood pressure and tolerability. CMR (including quantitative stress perfusion) will be performed at baseline and 6 months. The primary outcome is the between-group difference in change in stress MBF and MPR from baseline to 6 months. Secondary outcomes include change in six-minute walk distance and Seattle Angina Questionnaire-7 (SAQ-7) scores.

DISCUSSION: This study will provide evidence on whether Vericiguat can improve myocardial perfusion in patients with CMD and offer insights into its potential as a novel therapy for CMD.