Efficacy of mevinolin as adjuvant therapy for refractory familial hypercholesterolaemia.

Mevinolin, a potent inhibitor of cholesterol synthesis, was used as a therapeutic adjuvant in patients with refractory familial hypercholesterolaemia for an average period of 13 months. Sustained decreases in serum cholesterol of 23 and 31 per cent were achieved by doses of 20 mg and 40 mg/day respectively in 13 heterozygotes already on cholestyramine or after partial ileal bypass. Administration of 80 mg/day to three patients undergoing plasma exchange reduced peak serum cholesterol levels by 11.5 per cent in two homozygotes and by 17 per cent in a double heterozygote for familial hypercholesterolaemia and type III hyperlipoproteinaemia. The decrease in cholesterol was largely confined to low-density lipoprotein and no significant changes occurred in serum triglyceride or high-density lipoprotein cholesterol. Mevinolin was well-tolerated except in one patient who developed myositic symptoms; asymptomatic, transient elevations of serum enzymes were observed in five others. Short and long Synacthen tests showed no evidence that the drug impaired adrenocortical response to ACTH. These results indicate that mevinolin provides a safe and highly effective means of reducing LDL levels in patients with heterozygous familial hypercholesterolaemia refractory to conventional treatment but is less useful in homozygotes.