title: Cardiac allograft vasculopathy by intravascular ultrasound in heart transplant patients: substudy from the Everolimus versus mycophenolate mofetil randomized, multicenter trial.
abstract: OBJECTIVE
  A pre-planned substudy of a larger multicenter randomized trial was undertaken to compare the efficacy of everolimus with reduced-dose cyclosporine in the prevention of cardiac allograft vasculopathy (CAV) after heart transplantation to that of mycophenolate mofetil (MMF) with standard-dose cyclosporine.
  
  
  BACKGROUND
  CAV is a major cause of long-term mortality following heart transplantation. Everolimus has been shown to reduce the severity and incidence of CAV as measured by first year intravascular ultrasound (IVUS). MMF, in combination with cyclosporine, has also been shown to have a beneficial effect in slowing the progression of CAV.
  
  
  METHODS
  Study patients were a pre-specified subgroup of the 553-patient Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial who underwent heart transplantation and were randomized to everolimus 1.5 mg or MMF 3 g/day. IVUS was performed at baseline and at 12 months. Evaluable IVUS data were available in 189 patients (34.6%).
  
  
  RESULTS
  Increase in average maximal intimal thickness (MIT) from baseline to month 12 was significantly smaller in the everolimus 1.5 mg group compared with the MMF group (0.03 mm vs. 0.07 mm, p < 0.001). The incidence of CAV, defined as an increase in MIT from baseline to month 12 of greater than 0.5 mm, was 12.5% with everolimus versus 26.7% with MMF (p = 0.018). These findings remained irrespective of sex, age, diabetic status, donor disease, and across lipid categories.
  
  
  CONCLUSIONS
  Everolimus was significantly more efficacious than MMF in preventing CAV as measured by IVUS among heart-transplant recipients after 1 year, a finding, which was maintained in a range of patient subpopulations. CV surgery: transplantation, ventricular assistance, cardiomyopathy.
authors.affiliation: Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: Kobashigawaj@cshs.org.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Kobashigawa
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: Division of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Howard
authors.initials: H
authors.lastname: Eisen
authors.affiliation: Division of Experimental Therapeautics, Toronto Medical Hospital, Toronto, Ontario, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Ross
authors.affiliation: Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shoei-Shen
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Lipid Research Center, Laval University Medical Center, Quebec, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Cantin
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: James A
authors.initials: JA
authors.lastname: Hill
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Gaohong
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
mesh_terms: D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000517:prevention & control*; D000068338:Everolimus; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000000981:diagnostic imaging* / Q000517:prevention & control*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018084:Ultrasonography, Interventional
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus
keywords: cardiac allograft vasculopathy; everolimus; heart transplant; intravascular ultrasound