A multicenter comparison of lovastatin and cholestyramine therapy for severe primary hypercholesterolemia. The Lovastatin Study Group III.

This study compares lovastatin and cholestyramine resin therapy in patients with severe primary hypercholesterolemia. Two hundred sixty-four patients on lipid-lowering diets were randomized equally to receive 12 g of cholestyramine resin, 20 mg of lovastatin, or 40 mg of lovastatin, each twice a day. The mean reductions among the three groups after 12 weeks' treatment in levels of total plasma cholesterol (-17%, -27%, and -34%, respectively) and low-density lipoprotein cholesterol (-23%, -32%, and -42%, respectively) and the median reductions in apolipoprotein B levels (-21%, -28%, and -33%, respectively) were all significantly different between groups. Similar mean increases in high-density lipoprotein cholesterol levels (8%, 9%, and 8%, respectively) and median increases in apolipoprotein A-1 levels (7%, 6%, and 11%, respectively) were observed in all treatment groups. Cholestyramine resin treatment had no significant effect on very low-density lipoprotein cholesterol and apolipoprotein A-II levels and produced a median 11% increase in plasma triglyceride concentration; in contrast, administration of either 20 or 40 mg of lovastatin twice a day was associated with median reductions in very low-density lipoprotein cholesterol levels (-34% and -31%, respectively) and plasma triglyceride levels (-21% and -27%, respectively) and median increases in levels of apolipoprotein A-II (8% and 13%, respectively). Adverse events in all treatment groups were preponderantly in the gastrointestinal tract; gastrointestinal tract symptoms that could be attributed to therapy with a specific drug occurred in 58% of the cholestyramine resin group, 13% of the 20-mg lovastatin group, and 14% of the 40-mg lovastatin group. The only drug-attributable serious adverse event was a reversible myopathy in a patient taking 40 mg of lovastatin twice a day. We conclude that lovastatin is both more effective and better tolerated than cholestyramine resin in the treatment of primary hypercholesterolemia.