Simvastatin and cholestyramine in the long-term treatment of hypercholesterolaemia

After 6 weeks on a lipid-lowering diet, 20 outpatients with type II hyperlipoproteinaemia (18 type IIa) were randomized to treatment with cholestyramine 12 g b.i.d. (5 patients) or simvastatin (a new HMG-CoA reductase inhibitor) 40 mg q.p.m. (15 patients) for 12 weeks. From week 13 to week 20 nine patients in the simvastatin group and all patients in the cholestyramine group were treated with the combination of the two drugs. From week 21 to week 52 all patients were on monotherapy with simvastatin. Simvastatin treatment reduced low-density lipoprotein (LDL) cholesterol by 40% after 12 weeks, compared with 33% in the cholestyramine group. This difference was not significant. The total reductions of LDL-cholesterol on combination therapy were respectively 60% and 56% in each group. After 52 weeks LDL-cholesterol was still reduced by 36% (P less than 0.001) on monotherapy with simvastatin. Simvastatin also reduced triglycerides (TG) by 17% (P less than 0.05) and high-density lipoprotein (HDL) cholesterol was increased by 19% (P less than 0.01). No serious side effects were observed, and the new HMG-CoA reductase inhibitors may offer a new approach to the treatment of hypercholesterolaemia.