Combination drug therapy for familial combined hyperlipidemia

Study objective: To compare the efficacy of gemfibrozil and colestipol with gemfibrozil and lovastatin in patients with familial combined hyperlipidemia. Design: A prospective, randomized trial. Setting: An outpatient clinical research center in a tertiary care center. Patients: Seventeen patients with familial combined hyperlipidemia documented by studies of first-degree relatives; nine patients with type 2b hyperlipoproteinemia, and eight patients with type 4 hyperlipoproteinemia. Interventions: Baseline lipid, lipoprotein, and apolipoprotein levels were obtained during control periods on diet alone and on gemfibrozil therapy. Patients then received gemfibrozil and colestipol or gemfibrozil and lovastatin in a randomized order. Measurements and main results: In patients with type 2b hyperlipoproteinemia, gemfibrozil alone significantly reduced total cholesterol by 11%, and low density lipoprotein (LDL)-apolipoprotein B by 18%, did not change LDL-cholesterol, and raised high density lipoprotein (HDL)-cholesterol levels by 26%. Addition of either colestipol or lovastatin reduced LDL-cholesterol levels by 17% and 25%, respectively, compared to gemfibrozil alone. However, colestipol mitigated the HDL-cholesterol raising effect of gemfibrozil and did not further reduce LDL-apolipoprotein B levels. In contrast, addition of lovastatin caused an additional reduction of LDL-apolipoprotein B 19% compared with gemfibrozil alone. In patients with type 4 hyperlipoproteinemia, gemfibrozil alone reduced triglycerides by 40%, raised HDL-cholesterol by 26%, and increased LDL-cholesterol levels by 29%. The addition of either colestipol or lovastatin reduced LDL-cholesterol levels by 34% and 33%, respectively (compared with gemfibrozil alone), but greater reductions of LDL-apolipoprotein B (30% with lovastatin compared with 15% with colestipol, compared with gemfibrozil alone), and increases in HDL-cholesterol levels (8% increase with lovastatin compared with 10% decrease with colestipol, compared to gemfibrozil alone) were seen with the lovastatin combination. Conclusions: Although gemfibrozil with either colestipol or lovastatin favorably altered lipoprotein levels in patients with hypertriglyceriidemia and familial combined hyperlipidemia, the combination of gemfibrozil and lovastatin appeared superior overall.