Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival.
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.
Mehra
Mandeep R
MR
Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA. mmehra@ochsner.org
Uber
Patricia A
PA
Vivekananthan
Krishnamoorthy
K
Solis
Sergio
S
Scott
Robert L
RL
Park
Myung H
MH
Milani
Richard V
RV
Lavie
Carl J
CJ
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
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D017035:Pravastatin