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CXCR2 Inhibition - a novel approach to treating CoronAry heart DiseAse (CICADA): study protocol for a randomised

Jubin P Joseph1, Eliana Reyes2, Josephine Guzman3

  • 1British Heart Foundation Centre of Excellence, The Rayne Institute, St. Thomas' Hospital, London, SE1 7EH, UK. jpjoseph@gmail.com.

Trials
|October 13, 2017
PubMed

Insights

This study investigates AZD5069, a cysteine-X-cysteine chemokine receptor 2 (CXCR2) inhibitor, for its effects on coronary flow reserve in patients with coronary artery disease. The research aims to understand neutrophil-mediated inflammation

Area of Science:

  • Cardiovascular Medicine
  • Inflammation Research
  • Pharmacology

Background:

  • Neutrophils play a key role in atherosclerotic plaque development and rupture.
  • Lower neutrophil counts post-acute coronary syndrome correlate with better coronary flow reserve.
  • The impact of neutrophil inhibition on cardiovascular outcomes remains largely unexplored.

Purpose of the Study:

  • To evaluate the efficacy of AZD5069, a CXCR2 inhibitor, in improving coronary flow reserve.
  • To assess the effects of AZD5069 on coronary plaque inflammation and diastolic function.
  • To explore the role of neutrophil-mediated inflammation in coronary artery disease.

Main Methods:

  • A phase IIa, randomized, placebo-controlled, double-blind, single-centre study.
  • Ninety patients with coronary artery disease undergoing percutaneous coronary intervention.
  • Treatment with AZD5069 (40 mg twice daily) or placebo for 24 weeks, with coronary flow reserve measured by PET-CT.

Main Results:

  • Primary outcome: Change in coronary flow reserve assessed by 13N-ammonia PET-CT.
  • Secondary outcomes: Changes in the inflammatory component of coronary plaque and backward expansion wave (diastolic function).

Conclusions:

  • Coronary flow reserve may serve as a surrogate marker for the cardiovascular effects of CXCR2 inhibitors.
  • This study will enhance understanding of neutrophil-mediated inflammation in coronary artery disease.
  • The findings may inform future therapeutic strategies targeting neutrophil function in cardiovascular disease.
Abstract

Keywords:
AtherosclerosisCXCR2Coronary flow reserveCoronary physiologyNeutrophil function

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