Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia. Additive effects of compactin and cholestyramine.

We studied the effects of the bile acid sequestrant cholestyramine, alone and in combination with the experimental agent compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum levels of lipoproteins in 10 heterozygous patients with familial hypercholesterolemia. After cholestyramine treatment alone for 2 to 16 months, serum total and low-density lipoprotein cholesterol decreased by 20 and 28 per cent, respectively. With the addition of compactin for 12 weeks there was a 39 per cent total decrease in serum cholesterol from the control value--from 356 +/- 14 to 217 +/- 10 mg per deciliter (9.27 +/- 0.36 to 5.64 +/- 0.26 mmol per liter [mean +/- S.E.M.]; P less than 0.001)--and a 53 per cent decrease in low-density lipoprotein cholesterol--from 263 +/- 13 to 125 +/- 10 mg per deciliter (6.84 +/- 0.34 to 3.25 +/- 0.26 mmol per liter; P less than 0.001). High-density lipoprotein cholesterol, which had increased during cholestyramine treatment, remained at its higher level. No adverse effects were observed. If long-term safety can be demonstrated, the compactin-cholestyramine regimen may prove useful in heterozygous familial hypercholesterolemia. prove useful in heterozygous familial hypercholesterolemia.