Effects of simvastatin on plasma lipid, lipoprotein and apolipoprotein concentrations in hypercholesterolaemia

The effect of 24 weeks of treatment with simvastatin, a newHMG coenzyme A reductase inhibitor (dosages of 20 and40 mg day^–1)on serum lipid, lipoprotein and apolipoprotein A-I and B concentrationsas well as safety parameters and subjective side effects werestudied in 11 patients with familial (FH) and 10 patients withpolygenic hypercholesterolaemia (P-HC). The effects on plasmalipoprotein and apolipoprotein concentrations had already beenachieved after four weeks in both groups and then remained duringthe study. In FH, mean fasting plasma total cholesterol concentrationdecreased from 10·51 to 6·71 mmol l^–1 (36%),and in P-HC from 6·55 to 4·54 mmol l^–1 (31%)at 24 weeks (P<0·001). Mean plasma low density lipoprotein(LDL) cholesterol concentrations also decreased, in FH from8·87 to 5·05 mmol l^–1 (43%) and in P-HCfrom 4–97 to 3–12 mmol l^–1 (37%) at 24 weeks(P<0·001). Furthermore, apolipoprotein B concentrationsdecreased significantly from 2·21 to 1·57 g l^–1(29%)(P<0·001) in FH and from 1·53 to 1·09g l^–1 (29%) (P<0·01) in P-HC. Plasma high densitylipoprotein (HDL) cholesterol increased in both FH and P-HCduring treatment. Increases were seen in both the subfractionsHDL₂ and HDL₃. Simvastatin was well tolerated. No serious clinicalor laboratory adverse effects were observed. It is concludedthat 24 weeks of treatment with simvastatin in doses up to 40mg day^–1 effectively reduces plasma total and LDL cholesterolconcentrations without causing subjective or significant objectiveside effects. Thus, simvastatin may be of great interest infuture studies for prevention of coronary heart disease dueto hypercholesterolaemia.