Low-dose simvastatin is safe in hyperlipidaemic renal transplant patients

Hyperlipidaemia is common after renal transplantation, and becauseof its association with atherosclerosis, interest has increasedin the use of lipid-lowering drugs in transplant patients. Dietaryapproaches have not been consistently successful, and multiplepharmacotherapy and drug interactions have led to difficultiesin establishing lipid-lowering drug regimes. The statins reduceplasma cholesterol by inhibiting the rate-limiting step in cholesterolsynthesis, and although some side-effects have been reportedin their use after transplantation, the efficacy and safetyof low doses has not been formally established. A randomized single-blind placebo crossover study designed todetermine the safety and effectiveness of simvastatin in a singledaily 5-mg evening dose was therefore conducted in 26 stablerenal transplant patients, 14 of whom were receiving cyclosporinA. The results demonstrated no difference between total cholesterollevels in the baseline simvastatin and placebo periods: 7.97± 1.2 and 7.59±1.5 mmol/l respectively. After8 weeks of simvastatin, the total cholesterol declined significantlyto 6.72±0.87 mmol/l (P<0.001). A significant differencewas found when the placebo and simvastatin cholesterol levelswere compared at 4 and 8 weeks (P<0.01). LDL cholesterol decreased from 4.74 ± 0.87 to 3.78 ±0.78 mmol/l after 8 weeks on simvastatin (P<0.001), and apoB fell from 142 ± 31 to 112 ± 22 mg/dl (P<0.001).The difference in LDL cholesterol and apo B after 8 weeks ofsimvastatin when compared with the corresponding values on placebowas also significant (P<0.01). A slight but not significantincrement in HDL cholesterol from 1.10 ± 0.47 to 1.13± 55 mmol/l (NS) was seen after 8 weeks on simvastatin. Triglycerides and serum creatinine did not change during thestudy in any of the groups. Creatine kinase (CK.) remained inthe normal range (0–200 U/l), except for one patient nottaking cyclosporin who had a CK value slightly above the upperlimit of normal during the simvastatin period, without abnormalclinical signs. Repeated cyclosporin measurements remained withinthe therapeutic range (50–150 ng/ml). These results suggestthat low-dose simvastatin is effective and safe in reducingtotal cholesterol and LDL cholesterol in renal transplant patients.