title: Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival.
abstract: OBJECTIVE
  We sought to evaluate the relative effects of low doses of pravastatin (20 mg/day) and simvastatin (10 mg/day) on indices of cardiac allograft rejection. We further examined the relative efficacy and safety of these two drugs on lipid-lowering in heart transplantation.
  
  
  BACKGROUND
  The immunomodulatory effects of hydroxy methyl glutaryl-coenzyme A reductase inhibitors have been increasingly recognized. Previous studies have demonstrated an ameliorative influence of pravastatin on hemodynamically compromising rejection after heart transplantation. A recent observational trial suggested that simvastatin 20 mg/day was associated with trends to lower survival and more adverse effects than pravastatin 40 mg/day.
  
  
  METHODS
  In a 12-month prospective, open-label study, 50 heart transplant recipients received either open-label pravastatin 20 mg daily (n = 24) or simvastatin 10 mg daily (n = 26) within four weeks of transplantation. Indices of allograft rejection including treated rejection, rejection with hemodynamic compromise, noncellular rejection, and mean one-year biopsy score were compared between the two cohorts, as well as with a statin-naive control population (n = 37). Lipid levels, safety, and post-transplant outcomes were also assessed as secondary end points.
  
  
  RESULTS
  We found no significant differences in any allograft rejection parameter between the two groups. However, total low-density lipoprotein (LDL), but not high-density lipoprotein cholesterol or triglycerides, were lower in the simvastatin arm (-23% vs. -11%, p = 0.02). No cases of rhabdomyolysis or myositis occurred in either group. Survival at one year was similar in both treatment groups (91% for patients on pravastatin and 92% for patients on simvastatin). Both groups had better survival compared with the statin-naive control group (80%, p = 0.04).
  
  
  CONCLUSIONS
  Simvastatin (10 mg/day) and pravastatin (20 mg/day) are associated with similar beneficial effects on cardiac allograft rejection and one-year survival. At these doses, simvastatin decreases LDL cholesterol more so than pravastatin with no increase in adverse effects in heart transplantation.
authors.affiliation: Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA. mmehra@ochsner.org
authors.forename: Mandeep R
authors.initials: MR
authors.lastname: Mehra
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Uber
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Vivekananthan
authors.forename: Sergio
authors.initials: S
authors.lastname: Solis
authors.forename: Robert L
authors.initials: RL
authors.lastname: Scott
authors.forename: Myung H
authors.initials: MH
authors.lastname: Park
authors.forename: Richard V
authors.initials: RV
authors.lastname: Milani
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Lavie
mesh_terms: D000293:Adolescent; D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000628:therapy; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000401:mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D017035:Pravastatin