Design and rationale of the efficacy of endothelin receptor antagonism in treatment of coronary artery spasm: a randomized controlled trial (EDIT-CAS)

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Epicardial vasospasm in angina with no obstructive coronary artery disease (ANOCA) (n=100). Intervention: Bosentan vs. Placebo. Primary outcome: Absence of epicardial spasm at repeat spasm provocation testing.

Caïa Crooijmans; Tijn P.J. Jansen; Tim P. van de Hoef; Valeria Paradies; Annemiek de Vos; B Yosofi; Aysun Cetinyurek‐Yavuz; Hester M. den Ruijter; Marcel A.M. Beijk; Martijn Meuwissen; Niels van Royen; Suzette Elias‐Smale; Aukelien C. Dimitriu‐Leen; Peter Damman

doi:10.1016/j.ahj.2025.04.022

April 22, 2025American Heart JournalOpen Access

Design and rationale of the efficacy of endothelin receptor antagonism in treatment of coronary artery spasm: a randomized controlled trial (EDIT-CAS)

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Key result

EDIT-CAS trial tests whether 10-week bosentan prevents epicardial spasm in angina without obstructive CAD.

n=100

Why the study?

Targeted therapies for angina with vasomotor dysfunction are unavailable, and epicardial spasm is hypothesized to respond to endothelin receptor antagonism.

Does bosentan prevent epicardial spasm and improve symptoms in patients with epicardial vasospasm and continuing angina despite optimal medical treatment?

Study Design

Type

RCT (n=100)

Blinding

Double-blind

Randomization

1:1

Multicenter

Yes

Structured PICO

Does bosentan prevent epicardial spasm and improve symptoms in patients with epicardial vasospasm and continuing angina despite optimal medical treatment?

P

Population

100 patients with previously diagnosed epicardial vasospasm on a maximal triggering dose of 100 micrograms of acetylcholine and continuing angina(-like) symptoms at least once weekly despite optimal medical treatment (previous treatment with ≥2 daily anti-anginal medications, current treatment with at least 1).

I

Intervention

Bosentan 62.5 mg oral twice daily for 4 weeks, then up-titrated to 125 mg twice daily for 6 weeks (total 10 weeks duration), added to optimal regular care.

C

Comparator

Matching placebo oral twice daily for 10 weeks, added to optimal regular care.

O

Outcome

Successful treatment defined as the absence of epicardial spasm at repeat spasm provocation testing at 10 weeks.surrogate

The EDIT-CAS trial will evaluate whether the endothelin receptor antagonist bosentan can effectively prevent epicardial spasm and reduce symptoms in patients with refractory vasospastic angina.

Limitations

Only patients with epicardial spasm with maximal triggering dose of 100mcg acetylcholine at index coronary function test will be included, which may affect generalisability.
Bosentan is tested as an add-on therapy to at least one current anti-anginal drug.
Safety monitoring of patients on chronic bosentan therapy is quite extensive, meaning it will remain a second- or third-line therapy.
Only patients with epicardial spasm with maximal triggering dose of 100mcg acetylcholine at index CFT will be included, which may affect generalizability
Bosentan is tested as an add-on therapy
Extensive safety monitoring required for chronic bosentan therapy means it will remain a second- or third-line therapy

Implication

RCT tests bosentan for epicardial spasm prevention in refractory vasospastic angina; extends endothelin antagonism evaluation in non-obstructive CAD.

Abstract

BACKGROUND: Patients with angina and no obstructive coronary artery disease frequently have vasomotor dysfunction as the underlying mechanism for symptoms. Patients with vasomotor dysfunction have a high angina burden and their treatment frequently fails to reduce complaints sufficiently. Targeted therapies are currently unavailable due to heterogeneity in the patient population and incomplete understanding of the underlying pathophysiological mechanisms. One of the vasomotor dysfunction endotypes, epicardial spasm, is hypothesized to be a possible target for endothelin receptor antagonism treatment. METHODS: The EDIT-CAS trial is a registry based, double blind, randomised, placebo-controlled clinical trial and aims to compare the efficacy of 10 weeks of add-on bosentan treatment versus placebo to prevent epicardial spasm at repeat spasm provocation test. Secondary and explorative outcomes are the effect on anginal complaints, safety of bosentan treatment, changes in coronary reactivity and the relationship between baseline endothelin levels and treatment success. We will include 100 patients with previously diagnosed epicardial vasospasm on a maximal triggering dose of 100 micrograms of acetylcholine and continuing angina(-like) symptoms at least weekly despite optimal medical treatment. TRIAL REGISTRATION: The is registered in Clinical Trials Information System (2023-507782-25-00) and ClinicalTrials.gov (NCT06432452).

Discussion

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Cite This Study

Crooijmans et al. (2025) conducted an RCT in Epicardial vasospasm in angina with no obstructive coronary artery disease (ANOCA) (n=100). Bosentan vs. Placebo was evaluated on Absence of epicardial spasm at repeat spasm provocation testing.

synapsesocial.com/papers/6a1c549a27b545b111a9c014 https://doi.org/10.1016/j.ahj.2025.04.022

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Design and rationale of the efficacy of endothelin receptor antagonism in treatment of coronary artery spasm: a randomized controlled trial (EDIT-CAS)

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Design and rationale of the efficacy of endothelin receptor antagonism in treatment of coronary artery spasm: a randomized controlled trial (EDIT-CAS)

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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