CLINICAL-EXPERIENCE WITH SIMVASTATIN COMPARED WITH CHOLESTYRAMINE

Simvastatin (MK733), derived from lovastatin by substituting CH3 for H at the 2′ position, is a potent hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor. Its cholesterol-lowering effect in 40 patients with heterozygous familial hypercholesterolaemia was more pronounced (an LDL-cholesterol reduction of 43%) than that of cholestyramine monotherapy in a matched group of 20 patients (30% reduction). The combination of the 2 drugs for 50 patients who tolerated cholestyramine was even more effective (a 54% reduction of LDL-cholesterol). The other changes were as follows: total cholesterol (simvastatin [S] −36%, cholestyramine [C] −23%, both drugs in combination [S+C] −45%); HDL-cholesterol (S +16%, C +9%, S+C +20%); triglyceride (S −21%, C +11%, S+C −17%); and the apolipoprotein B/apolipoprotein A ratio (S −51%, C −39%, S+C −67%). Cholestyramine caused more gastrointestinal adverse effects (12 of 20 patients), whereas a transaminase increase was seen both with cholestyramine (2 of 20 patients) and simvastatin (3 of 40 patients) and with the combination (6 of 50 patients).