Mevinolin plus colestipol in therapy for severe heterozygous familial hypercholesterolemia.
Twelve patients with severe heterozygous familial hypercholesterolemia, in whom other hypolipidemic drug therapy had failed to reduce serum cholesterol levels to less than 300 mg/dL, were sequentially treated with mevinolin (a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis) and colestipol. In ten patients receiving 80 mg/d of mevinolin, plasma cholesterol concentrations decreased 33%, from 487 +/- 27 (SE) mg/dL to 326 +/- 16 mg/dL. Additional therapy with colestipol resulted in a further 18% decrease, to 269 +/- 13 mg/dL. Concentrations of low density lipoprotein (LDL) cholesterol decreased in parallel (54% decrease on combined drug therapy). Plasma concentrations of high density lipoprotein cholesterol did not change significantly, but the LDL:HDL ratio decreased from 8.2 in patients on diet only to 3.8 in patients treated with mevinolin and colestipol. In seven patients treated with 40 mg/d of mevinolin, concentrations of LDL cholesterol decreased by 33%; combined therapy resulted in a further 20% decrease (46% reduction from the level achieved with diet only). No consistent side effects have been noted in up to 24 months of therapy. Combined therapy with mevinolin and colestipol promises to be effective for heterozygous familial hypercholesterolemia.