Efficacy and muscle safety of fluvastatin in cyclosporine-treated cardiac and renal transplant recipients: an exercise provocation test.
BACKGROUND
Dyslipidemia is found in the majority of renal and cardiac transplant recipients. Although 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors significantly lower low-density lipoprotein cholesterol (LDL-C) levels, such treatment has been associated with muscle toxicity, especially when used in combination with cyclosporine (CsA). We investigated the efficacy and muscle safety of fluvastatin, a new 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, in CsA-treated transplant recipients.


METHODS
The efficacy was determined by measuring the lipid profile before and after 8 weeks of fluvastatin therapy. As parameter for possible muscle damage, the rise in serum levels of the muscle proteins creatine kinase and myoglobin was measured after an exercise provocation test (30 min on a bicycle ergometer at 60% of their maximal work load) before and during fluvastatin therapy. Nineteen CsA-treated renal and cardiac transplant recipients with hypercholesterolemia were selected.


RESULTS
After 8 weeks of treatment with a dose of fluvastatin necessary to reduce LDL-C below 3.5 mmol/L (20 mg for 3 and 40 mg for 16 patients), total cholesterol was lowered by 20% and LDL-C by 30%, and HDL2-C was increased by 35% (all P<0.01). The rise in creatine kinase after exercise before and during fluvastatin therapy was, respectively, 40% and 51%, and the rise in myoglobin was 64% and 50%. These rises were not significantly different. Hence, there was no indication for subclinical muscle pathology by fluvastatin use. Fluvastatin was well tolerated, and no adverse effects on liver or kidney function were found.


CONCLUSIONS
Fluvastatin can effectively lower LDL-C in CsA-treated renal and cardiac transplant recipients, without demonstrable adverse effects.
Schrama
Y C
YC
Department of Nephrology, University Hospital Utrecht, The Netherlands. Y.C.Schrama@digd.azu.nl
Hené
R J
RJ
de Jonge
N
N
Joles
J A
JA
Van Rijn
H J
HJ
Bär
D R
DR
Ververs
T F
TF
Van Tol
A
A
Koomans
H A
HA
D000328:Adult; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005080:Exercise Test / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D000077340:Fluvastatin; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects*; D009135:Muscular Diseases / Q000139:chemically induced
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007166:Immunosuppressive Agents; D007211:Indoles; D000077340:Fluvastatin; D016572:Cyclosporine