The effect of atorvastatin on serum lipids and lipoproteins in patients with homozyous familial hypercholesterolemia undergoing LDL-apheresis therapy

The efficacy of atorvastatin, a new hydroxymethylglutaryl (HMG)-CoA reducta se inhibitor, in reducing serum lipid levels, modifying lipoprotein composi tion, and suppressing cholesterol synthesis was evaluated in patients with homozygous familial hypercholesterolemia (homozygous FH) undergoing LDL-aph eresis therapy. Atorvastatin was given in escalating doses (10, 20, and 40 mg/day) to nine patients with homozygous FH. Five of nine patients responde d well to atorvastatin; four of these patients were receptor-defective and the remaining one was receptor-negative. The change in LDL-cholesterol in t he receptor-defective patients averaged -20.6% compared to the baseline lev el at the highest dose of atorvastatin. Of five receptor-negative type pati ents, only one showed good response to atorvastatin therapy with a LDL-chol esterol reduction of 14.9%. Although the other four receptor-negative patie nts did not show a change in LDL-cholesterol, all of them exhibited a consi derable increase in HDL-cholesterol. All patients showed reduced urinary ex cretion of mevalonic acid, suggesting that atorvastatin decreases LDL-chole sterol by inhibiting cholesterol biosynthesis even where LDL-receptor activ ity is not present. Atorvastatin also decreased serum triglycerides in both receptor-negative and defective patients, especially in the latter. As cho lesterol level rebounds quickly after each apheresis procedure, a combinati on therapy using atorvastatin and apheresis may increase the efficacy of th e apheresis treatment, improving cost-benefit effectiveness by reducing the frequency of the apheresis treatment. (C) 2000 Elsevier Science Ireland Lt d. All rights reserved.