title: Long-term endothelin receptor antagonism attenuates coronary plaque progression in patients with early atherosclerosis.
abstract: OBJECTIVE
  The purpose of the current study was to determine if long term treatment with an endothelin-A (ETA) receptor antagonist attenuates the progression of coronary plaques in patients with coronary endothelial dysfunction.
  
  
  METHODS
  Thirty-five patients with non-obstructive coronary disease and coronary endothelial dysfunction were randomized in a double blind manner to treatment with placebo or ETA receptor antagonist Atrasentan (10 mg) for six months. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Normalized mean total atheroma volume (TAVMEAN), percent atheroma volume (PAV) and changes of atheroma volume were assessed by intravascular ultrasound (IVUS) at baseline and 6-month follow-up.
  
  
  RESULTS
  In segments with coronary endothelial dysfunction, there was a significant decrease in normalized TAVMEAN and PAV at six months from baseline in the Atrasentan group compared to the placebo group median (IQR) -2.00 mm(3) (-7.28, 2.53.) vs 9.11 mm(3) (1.23, 14.05), p=0.0024 and 0.955% (-3.43, 1.70) vs 3.85% (-0.39, 14.59) p=0.010. There was no change in normalized TAV or PAV in the segments with normal endothelial function.
  
  
  CONCLUSIONS
  This study demonstrates that 6-month treatment with Atrasentan attenuates progression of coronary plaque in segments with endothelial dysfunction.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First Street, SW, Rochester, MN 55905, United States.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Yoon
authors.forename: Martin
authors.initials: M
authors.lastname: Reriani
authors.forename: Gössl
authors.initials: G
authors.lastname: Mario
authors.forename: Charanjit
authors.initials: C
authors.lastname: Rihal
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gulati
authors.forename: Ryan
authors.initials: R
authors.lastname: Lennon
authors.forename: Jonella M
authors.initials: JM
authors.lastname: Tilford
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy*; D000077868:Atrasentan; D018450:Disease Progression; D004311:Double-Blind Method; D042241:Early Diagnosis; D065130:Endothelin A Receptor Antagonists; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D011759:Pyrrolidines / Q000008:administration & dosage*; D044022:Receptor, Endothelin A / Q000502:physiology; D013997:Time Factors
chemical_list: D065130:Endothelin A Receptor Antagonists; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D000077868:Atrasentan
keywords: Endothelial function; Endothelin receptor (ET(A)) antagonist; Intravascular ultrasound (IVUS); Normalized mean total atheroma volume (TAV(MEAN)); Percent atheroma volume (PAV)