Effects of HMG-CoA reductase inhibitors in hypercholesterolemic patients on hemodialysis

Effects of HMG-CoA reductase inhibitors in hypercholesterolemic patients on hemodialysis. The efficacy of lovastatin and simvastatin, competitive inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 40 hemodialysis (HD) patients displaying hypercholesterolemia and moderate hypertriglyceridemia (selection of 40 patients required screening of 700 hemodialysis patients). After a four-week placebo period, lovastatin or simvastatin was administered to two groups of 20 patients in increasing doses over a period of three months Thirty-six patients completed the study. Lovastatin (1st month 20 mg; 2nd and 3rd months 40mg day-1) and simvastatin (1st month 10 mg, 2nd month 20mg and 3rd month 40mg day-1) reduced total serum cholesterol from 280.3 ± 9.4 to 213.0 ± 6.7 (-24%) and 295.0 ± 12.2 to 202.3 ± 8.9 mg/dl (-31.4%), LDL cholesterol from 161.9 ± 10.7 to 112.1 ± 7.9 (-30.8%) and 181.8 ± 14.7 to 107.4 ± 8.1 mg/dl (-40.9%), as well as apolipoprotein B (apo B) from 116.0 ± 6.6 to 83.3 ± 3.7 (-28.2%) and 134.4 ± 8.2 to 84.1 ± 5.3 mg/dl (-37.4%), respectively. Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.63 ± 0.02 vs. 0.71 ± 0.05 and 0.63 ± 0.02 vs. 0.66 ± 0.02, respectively). Another remarkable effect was the reduction of cholesterol concentration in VLDL (72.4 ± 8.9 vs. 47.3 ± 6.8 [lovastatin] and 78.3 ± 11.1 vs. 50.7 ± 8.8 mg/dl [simvastatin], respectively). Therefore, the ratio of triglycérides/cholesterol in VLDL increased (3.2 ± 0.2 vs. 3.8 ± 0.3 and 3.2 ± 0.2 vs. 4.0 ± 0.2, respectively), indicating VLDL formation poor in cholesterol and rich in triglycerides. The main difference between the two drugs was that only simvastatin significantly reduced triglycerides but increased HDL cholesterol and apolipoprotein A-I. Although one patient developed a moderate increase in hepatic transaminases, the other 35 patients had no notable side effects. Measurement of simvastatin plasma levels 13.4 hours after drug administration showed plasma values between 4 and 45 ng/ml (in controls not detectable after 12 hr). At present, it appears that there are only a few selected patients with high serum cholesterol level among all HD patients who could be candidates for the treatment with HMG-CoA reductase inhibitors