The efficacy of
simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl
glutaryl coenzyme A reductase, was investigated in 12 patients treated with
continuous ambulatory peritoneal dialysis (
CAPD), displaying
hypercholesterolemia and moderate
hypertriglyceridemia. After a 4-week placebo period,
simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1).
Simvastatin reduced total serum
cholesterol (300.0 +/- 15.5 vs. 193.0 +/- 8.0; -35%),
LDL cholesterol (203.8 +/- 13.0 vs. 104.7 +/- 6.0; -48.0%) as well as
apolipoprotein B (132.3 +/- 6.6 vs. 77.8 +/- 2.7 mg/dl; -40%). Furthermore, the ratio of
LDL apo B/
LDL cholesterol increased significantly (0.55 +/- 0.016 vs. 0.64 +/- 0.027). Another remarkable effect was the reduction of
cholesterol concentration in VLDL (47.8 +/- 5.6 vs. 30.4 +/- 5.2; -35%). Therefore, the ratio of
triglycerides/
cholesterol in VLDL increased (3.57 +/- 0.3 vs. 4.28 +/- 0.29), indicating VLDL formation poor in
cholesterol and rich in
triglycerides. However,
HDL cholesterol increased significantly from 48.6 +/- 4.4 to 57.9 +/- 5.3 mg/dl (23%).
Lipoprotein(a) levels were increased as compared to controls (420 +/- 73 vs. 145 +/- 26 U/l), but were not influenced significantly by
simvastatin treatment (539 +/- 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of
simvastatin plasma levels 12 h after
drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that
CAPD patients with high serum
cholesterol are good candidates for the treatment with
HMG-CoA reductase inhibitors.