title: Safety and efficacy of early aggressive versus cholesterol-driven lipid-lowering strategies in heart transplantation: a pilot, randomized, intravascular ultrasound study.
abstract: BACKGROUND
  Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold.
  
  
  METHODS
  This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters.
  
  
  RESULTS
  Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02).
  
  
  CONCLUSIONS
  Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries.
authors.affiliation: Cardiovascular Department, University of Bologna, Bologna, Italy. luciano.potena2@unibo.it
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Francesco
authors.initials: F
authors.lastname: Grigioni
authors.forename: Paolo
authors.initials: P
authors.lastname: Ortolani
authors.forename: Gaia
authors.initials: G
authors.lastname: Magnani
authors.forename: Francesca
authors.initials: F
authors.lastname: Fabbri
authors.forename: Marco
authors.initials: M
authors.lastname: Masetti
authors.forename: Fabio
authors.initials: F
authors.lastname: Coccolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Fallani
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Teresa
authors.initials: T
authors.lastname: Ionico
authors.forename: Francesco
authors.initials: F
authors.lastname: Saia
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.forename: Angelo
authors.initials: A
authors.lastname: Branzi
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012189:Retrospective Studies; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014652:Vascular Diseases / Q000517:prevention & control
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008077:Lipoproteins, LDL; D000077340:Fluvastatin; D002784:Cholesterol; D003402:Creatine Kinase