Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: Additive effects of combination treatment on lipid regulation

The most appropriate therapy for combined hyperlipidemia remains to be dete rmined. We compared the lipid-regulating effects of gemfibrozil and lovasta tin in 30 patients with familial combined hyperlipidemia (FCHL) in a random ized, double-blind, placebo-controlled crossover study including 8-week cou rses of one drug followed by a washout period and a crossover phase to the alternate drug. After completion of the trial, open-label combination thera py was given for up to 12 months. Lovastatin was more efficacious than gemf ibrozil in the reduction of total cholesterol (23% v 9%, P <.001) and low-d ensity lipoprotein (LDL) cholesterol (28% v 2%, P <.001), whereas gemfibroz il surpassed lovastatin in the reduction of triglycerides (48% v 0%, P <.00 1) and very-low-density lipoprotein (VLDL) cholesterol (50% v 19%, P =.005) and the increase of high-density lipoprotein (HDL) cholesterol (18% v4%, P =.005). Lovastatin caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug-induced changes in lipoprotein composition indic ated that gemfibrozil reduced both the number and size of VLDL particles an d lovastatin decreased the number of LDL particles, Combined treatment was safe and had additive effects on lipids, causing significant (P <.001) redu ctions in total cholesterol (32%), triglycerides (51%), LDL cholesterol (34 %), and apo B (26%) and an increase in HDL cholesterol (19%). Target LDL ch olesterol levels were achieved only in 11% of patients given gemfibrozil al one and triglycerides decreased to target levels in 22% after lovastatin al one, whereas combined therapy normalized both lipid fractions in 96% of pat ients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels b ut favorably influences the putative atherogenic alterations of lipoprotein composition that are related to hypertriglyceridemia. Conversely lovastati n markedly decreases LDL cholesterol but has little effect on triglyceride- rich lipoproteins. Combination treatment safely corrects all of the lipid a bnormalities in most patients. Copyright (C) 1999 by W.B. Saunders Company.