Effect of combined therapy with bezafibrate and cholestyramine on low-density lipoprotein metabolism in type IIa hypercholesterolemia.

This study was designed to examine the influence of combined therapy with bezafibrate and cholestyramine on plasma lipids and on the metabolism of low-density lipoprotein (LDL). Twenty-one type II hyperlipidemic subjects were treated with bezafibrate alone or in combination with cholestyramine. A 17% fall in plasma cholesterol was seen with bezafibrate, and addition of cholestyramine produced an additional 9% reduction in this lipid. The effectiveness of the combination therapy was mediated through a 47% decrement in very-low-density lipoprotein (VLDL) cholesterol, a 37% reduction in LDL cholesterol, and a 15% increase in the level of that lipid in high-density lipoprotein (HDL). Plasma triglyceride fell 43% when bezafibrate was given alone, and did not change further when cholestyramine was added. The metabolism of LDL was examined in nine individuals to determine the mechanism underlying these changes. No significant modification in LDL synthetic rate was incurred with either drug regimen, whereas the fractional catabolic rate of LDL via the receptor pathway rose by 66% with bezafibrate alone and by 79% (compared to baseline) following the addition of cholestyramine. Plasma HDL rose during bezafibrate therapy due to an increase in the HDL3 subfraction. Compositional analysis of LDL showed a reduction in cholesterol ester and an increase in triglyceride and phospholipid during combined drug therapy. These results demonstrate that combined therapy with bezafibrate and cholestyramine markedly improves the lipoprotein profile in type II hyperlipidemia. The drugs appear to be complementary in their actions upon the LDL receptor pathway.