Low-dose lovastatin safely lowers cholesterol after cardiac transplantation.
Hypercholesterolemia occurs in many cardiac transplant patients and may aggravate graft coronary arteriopathy as well as contributing to peripheral vascular disease. Lovastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase, in doses of 40-80 mg/day effectively lowers cholesterol in the general cardiac population but has been associated with rhabdomyolysis in cardiac transplant recipients. To determine whether lower doses of lovastatin would be effective and safe for lowering cholesterol after cardiac transplantation, 44 patients with blood cholesterol greater than 200 mg/dl at least 6 months after cardiac transplantation received 10-20 mg lovastatin daily. In addition, lovastatin enzyme inhibitor level was assayed in six patients to determine whether metabolism of the drug was abnormal. Lovastatin decreased total cholesterol by 28% from 282 +/- 54 to 208 +/- 62 mg/dl (p less than 0.005), primarily because of reduction in the low-density lipoprotein fractions, and was well-tolerated without any symptoms or abnormal creatine phosphokinase levels in 43 of 44 patients. One patient developed rhabdomyolysis and reversible renal failure when lovastatin was increased to 40 mg daily. Enzyme inhibitor levels in the six transplant patients were 4.2-7.8 times higher than those measured in normal volunteers. Low-dose lovastatin effectively lowers cholesterol in patients after transplantation, but metabolism is altered, perhaps by cyclosporine. Monitoring of enzyme inhibitor levels may be required to allow safe administration of this drug to cardiac transplant recipients.
Kobashigawa
J A
JA
Division of Cardiology, UCLA School of Medicine 90024-1679.
Murphy
F L
FL
Stevenson
L W
LW
Moriguchi
J D
JD
Kawata
N
N
Kamjoo
P
P
Brownfield
E
E
Wilmarth
J
J
Leonard
L
L
Chuck
C
C
D002784:Cholesterol / Q000097:blood; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D006937:Hypercholesterolemia / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008148:Lovastatin / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
D007166:Immunosuppressive Agents; D002784:Cholesterol; D008148:Lovastatin