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Updated: Jun 14, 2025

Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
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Zibotentan in Microvascular Angina: A Randomized, Placebo-Controlled, Crossover Trial.

Andrew Morrow1, Robin Young2, George R Abraham3

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Circulation
|September 1, 2024
PubMed
Summary

Zibotentan did not improve exercise duration in patients with microvascular angina. The drug was associated with increased adverse events and did not demonstrate efficacy in this patient population.

Keywords:
angina with no obstructive coronary arteriesendothelin receptor antagonistexercise testgeneticsmicrovascular anginapharmacotherapy

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Area of Science:

  • Cardiology
  • Pharmacology
  • Genetics

Background:

  • Microvascular angina is linked to endothelin system dysregulation, affecting myocardial blood flow and quality of life.
  • The G allele of SNP RS9349379 increases endothelin-1 (ET-1) gene expression, potentially raising ET-1 levels.
  • The efficacy and safety of zibotentan, an ET-A receptor antagonist, for microvascular angina remain uninvestigated.

Purpose of the Study:

  • To evaluate the efficacy and safety of zibotentan in treating microvascular angina.
  • To assess the impact of zibotentan on exercise capacity in patients with microvascular angina.
  • To investigate the relationship between RS9349379 genotype and treatment response.

Main Methods:

  • A double-blind, placebo-controlled, crossover trial involving patients with microvascular angina.
  • Participants were selected for a 50% G allele frequency of the RS9349379 polymorphism.
  • The primary outcome was the change in treadmill exercise duration, with secondary outcomes assessing other clinical measures.

Main Results:

  • Zibotentan (10 mg daily) did not significantly improve exercise duration compared to placebo (difference of -4.26 seconds, P=0.5871).
  • No improvements were observed in secondary efficacy outcomes with zibotentan treatment.
  • Zibotentan led to a higher incidence of adverse events (60.2% vs. 14.4%) and reduced blood pressure.

Conclusions:

  • Short-term treatment with zibotentan (10 mg daily) is not beneficial for patients with microvascular angina.
  • The observed adverse events were common and target-related, suggesting potential safety concerns.
  • Further research may be needed to explore alternative therapeutic strategies for microvascular angina.