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Combination Drug Therapy for Familial Combined Hyperlipidemia

Cara East, MD; David W. Bilheimer, MD; and Scott M. Grundy, MD, PhD
[+] Article and Author Information

Grant Support: Partial support by National Institutes of Health grants HL 29252 and MO1-RR00633 (General Clinical Research Center); Public Health Service training grant AM 07307; the Southwestern Medical Foundation; the Moss Heart Foundation; and Parke-Davis, a division of Warner-Lambert Company.

Requests for Reprints: Scott M. Grundy, MD, PhD, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235.

Current Author Addresses: Drs. East and Grundy: Department of Internal Medicine and Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas TX 75235.

Dr. Bilheimer: Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75235.


Ann Intern Med. 1988;109(1):25-32. doi:10.7326/0003-4819-109-1-25
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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 hypertriglyceridemia and familial combined hyperlipidemia, the combination of gemfibrozil and lovastatin appeared superior overall.

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