Efficacy and Mechanisms of Macitentan for Non-Coronary Obstructive Angina

Обзор

Angina with non-obstructive coronary arteries (ANOCA) is highly prevalent, impairing quality of life and independently associated with cardiovascular events, yet effective treatments are lacking. The endothelin-1 (ET-1)-endothelin receptor (ETR) system is pivotal in ANOCA pathogenesis. Preclinical studies show that ETR blockade or pericyte-specific knockout of ETA receptor improves coronary microcirculatory function in models of myocardial ischemia-reperfusion and diabetes. Clinical evidence indicates ETR antagonists can enhance microvascular endothelial function and myocardial perfusion in ANOCA patients. However, prior studies diagnosed ANOCA based only on symptoms and angiography without precise microvascular functional assessment. Early ETR antagonists also showed frequent adverse effects (e.g., edema, headache), reducing treatment satisfaction. To address this, the investigators will conduct an open-label, single-center, single-arm trial using invasive coronary microcirculatory function testing to accurately phenotype ANOCA and assess microvascular changes. Patients on standard therapy will receive macitentan-a novel ETR antagonist with improved vasodilatory efficacy and safety-to evaluate its effects on coronary microcirculatory function, angina symptoms, and adverse events. Additionally, the investigators will perform multi-omics profiling (proteomics, transcriptomics, metabolomics) on patient blood samples to identify molecular signatures linked to ANOCA subtypes and treatment response, providing evidence for precision intervention strategies in ANOCA.

Вмешательства

• Препарат Macitentan 10 mg tablet, once daily.
  After the patient signed an informed consent form, Macitentan was given as an oral medication (10 mg once daily) for a period of 4 weeks

Первичные конечные точки

• Changes in coronary microcirculation function parameters assessed by CFR from baseline to week 4 [Срок оценки: the duration of hospital stay, an expected average of 1 week; 4-week follow-up]
• Changes in coronary microcirculation function parameters assessed by IMR from baseline to week 4 [Срок оценки: the duration of hospital stay, an expected average of 1 week; 4-week follow-up]

Вторичные конечные точки (2)

• Change in Score of the Seattle Angina Questionnaire (SAQ) [Срок оценки: Endpoint events before administration of macitentan, 1 week and 4 weeks after administration, and 4 weeks after drug withdrawal.]
• Re-hospitalization due to angina pectoris or heart failure, myocardial infarction, and cardiac death. [Срок оценки: Endpoint events at 1 week and 4 weeks after administration of macitentan, and 4 weeks after drug withdrawal.]

Критерии участия

Критерии включения

• Age 18-75 years old.
• With typical angina symptoms.
• Excluding obstructive coronary lesions (coronary stenosis ≤50% or FFR ≥0.8) by CAG.
• Coronary microcirculatory function was confirmed via pressure wire-based thermodilution technique.（Patients were classified into subtypes based on coronary microcirculatory function indices: 1) Type I: CFR ≥ 2.5 and IMR < 25; 2) Type II: CFR ≥ 2.5 and IMR ≥ 25; 3) Type III: CFR < 2.5 and IMR < 25; 4) Type IV: CFR < 2.5 and IMR ≥ 25.）
• Sign a written informed consent form.

Критерии исключения

• Pregnant or lactating women.
• History of heart attack within the last 90 days.
• Severe heart disease (e.g., moderate to severe heart failure, severe heart valve disease).
• Severe renal impairment (GFR <30 ml/min/1.73m2).
• Severe liver disease (Child-Pugh class C).
• Moderately severe anaemia (haemoglobin concentration <90 g/L).
• Participation in another drug intervention trial study within the last 90 days.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• China-Japan Friendship Hospital — Пекин

Идентификаторы

NCT: NCT07392281 · 2025-KY-351

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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