A preliminary report of the safety and efficacy of fluvastatin for hypercholesterolemia in renal transplant patients receiving cyclosporine

Abstract

Hypercholesterolemia is common following renal transplantation and undoubtedly contributes to morbidity and mortality due to occlusive atherosclerosis in these patients. Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are more tolerable as low density lipoprotein cholesterol (LDL-C)-lowering agents than other classes of drugs, their use in transplant patients has been limited due to potentially serious interactions with cyclosporine. Fluvastatin is the first wholly synthetic HMG-CoA reductase inhibitor. Because it has a shorter half-life and greater protein-binding capacity than other drugs of this class and has no active circulating metabolites, fluvastatin may be safer than other HMG-CoA reductase inhibitors in this group of patients. To study this question, 19 renal transplant recipients (age, 21-70 years) with hypercholesterolemia (LDL-C > 180 mg/dL; triglycerides < 400 mg/liter) were entered into a 14-week active-treatment period with fluvastatin at 20 mg/day following dietary stabilization and a 3-week placebo washout period. Changes in LDL-C levels were compared with those obtained in control hypercholesterolemic subjects treated in the same way. The lipid-lowering ability of fluvastatin was not imparied in these patients, indicating a lack of interaction with cyclosporine. Mean liver enzyme levels, creatine phosphokinase (CPK), and creatine did not change significantly from baseline. Two subjects experienced myalgias without CPK elevations, and another subject experienced an asymptomatic increase in CPK to > 10 times the upper limit of normal, related to exercise. In conclusion, fluvastatin safely and effectively lowers elevated LDL-C levels in renal transplant recipients.