Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease

Abstract

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.