Rationale and Design of the Vasospastic Angina Treatment by Endothelin Receptor Antagonism (VERA) Trial

Abstract Background Pharmacological treatment of patients diagnosed with vasospastic angina (VSA) or microvascular angina (MVA) is challenging and often patients remain symptomatic. Endothelin (ET)-1 plays an important role in the regulation of the vascular tone and stimulation of ET-1 receptors can induce a potent and long-lasting vasoconstriction. Macitentan is a potent, inhibitor of the ETA receptor. Purpose This prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept trial is designed to investigate macitentan as a potential novel treatment for patients with VSA due to epicardial spasm or MVA due to microvascular spasm, together defined as coronary artery spasm (CAS).Methods and Results A total of 30 patients with CAS will receive treatment with either 10 mg of macitentan daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in random order. The primary outcome is the reduction in angina, calculated as (1) the frequency of angina attacks * severity (on a VAS scale 1-10); and (2) the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10) during medication use (macitentan or placebo) up to 2 weeks after discontinuation of the study medication. The primary analysis will assess the within-subject differences in the burden of anginal symptoms following treatment with macitentan versus placebo.Conclusions The VERA trial will be the first to evaluate the efficacy of the ETA receptor antagonist, macitentan, in the treatment of VSA due to epicardial spasm and MVA due to microvascular spasm.Trial Registration trialregister.nl, Identifier: NL7546. Registration date: 20 February 2019.