Low-dose colestipol plus fenofibrate: effects on plasma lipoproteins, lecithin:cholesterol acyltransferase, and postheparin lipases in familial hypercholesterolemia

Effects on plasma lipoproteins, lecithin:cholesterol acyltransferase (LCAT), and postheparin lipase (LPL and HTGL) activities were studied in 18 patients with familial hypercholesterolemia during 8-week treatment periods with colestipol (15 g/d), fenofibrate (0.25 g/d), and colestipol plus fenofibrate. Lipoprotein lipids and apolipoproteins were determined by standard procedures, LCAT by a self-substrate method, and lipases by nonradioisotopic methods. Colestipol and fenofibrate, each given independently, caused similar percentage decreases in LDL cholesterol and apolipoprotein B: -18.4% and -8.6% v -17.4% and -10.6% Colestipol increased the VLDL cholesterol concentration, whereas fenofibrate reduced this parameter but increased HDL cholesterol and apolipoprotein A-I levels. The combination of both drugs led to a substantial fall in LDL cholesterol (-36.8%) and in apolipoprotein B (-28.3%) and maintained the other effects of fenofibrate on VLDL and HDL. Colestipol, given independently or with fenofibrate, produced an increase of the fractional esterification rate of the LCAT enzyme (+25.3% and +36.2%). Fenofibrate stimulated the postheparin LPL enzyme by +16.1% and +21.7%, respectively. This study indicates the complementarity in effectiveness when both drugs were administered together. The appropriate reduction in LDL was combined with the favorable effects on HDL in familial hypercholesterolemia.