Rationale and design of the vericiguat in vasospastic angina (ViVA) trial: A double-blind placebo-controlled randomized cross-over study.

BACKGROUND

Coronary vasospasm is highly prevalent in patients with angina and no obstructive coronary arteries (ANOCA). In the pathophysiology of coronary vasospasm, endothelial dysfunction and vascular smooth muscle cell hyperreactivity may cause an imbalance between vasodilation and vasoconstriction. Within this pathophysiology, nitric oxide is crucial. Nitric oxide activates soluble guanylate cyclase, which through the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, reduces intracellular calcium levels in vascular smooth muscle cells, resulting in vasodilation. sGC stimulators, such as vericiguat, enhance the sensitivity of soluble guanylate cyclase to nitric oxide. Vericiguat was shown to be well tolerated, safe, and clinically effective in both heart failure patients as well as in patients with coronary artery disease. We hypothesize that vericiguat restores the balance between vasodilation and vasoconstriction and thereby reduces coronary spasm episodes in ANOCA patients.

METHODS

In the Vericiguat in Vasospastic Angina trial, we will assess the impact of vericiguat on endothelial function and microvascular vasodilator responses, angina and quality of life. Additionally, we will evaluate the tolerability and safety of vericiguat in patients with coronary vasospasm as the pathophysiological substrate of ANOCA. 50 patients will be included in the trial, and will be randomized in a 1:1 ratio to placebo treatment first, followed by vericiguat treatment, or vericiguat treatment first, followed by placebo treatment.

TRIAL REGISTRATION: The Vericiguat in Vasospastic Angina trial is registered at ClinicalTrials.gov ID NCT06415227.