Issue 176 Item 15 Gemcabene Safely Increases HDL, Decreases LDL Levels

Patients with baseline triglyceride levels of 200 mg/dL or more who were treated with 150 mg gemcabene daily had an 18% increase in serum HDL cholesterol levels and a 27% reduction in serum triglyceride levels.

A new lipid-altering agent, gemcabene, safely increases HDL cholesterol levels and decreases LDL cholesterol and triglyceride levels in patients with low HDL cholesterol, according to a report in the September 1st issue of The American Journal of Cardiology.

Gemcabene, whose mechanism of action has yet to be established, raises HDL cholesterol level and lowers LDL cholesterol, triglyceride, and apolipoprotein C-III levels in rats, the authors report, and phase I studies showed the drug to be well-tolerated at doses up to 1500 mg/day.

Dr. Harold E. Bays from Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky and colleagues in the Gemcabene Study Group investigated the efficacy and tolerability of gemcabene at doses ranging from 150 to 900 mg daily in 161 patients with HDL cholesterol levels below 35 mg/dL in a 12-week placebo-controlled trial.

"The primary efficacy parameter evaluated was the percent change from baseline in serum HDL cholesterol levels," the investigators write, "because clinical improvement in HDL cholesterol levels may further reduce coronary heart disease risk above that achieved with LDL cholesterol lowering."

Patients with baseline triglyceride levels of 200 mg/dL or more who were treated with 150 mg gemcabene daily had an 18% increase in serum HDL cholesterol levels and a 27% reduction in serum triglyceride levels, the authors report.

Patients treated with higher doses of gemcabene did not experience significant increases in HDL cholesterol, the report indicates, and patients with baseline triglyceride levels below 200 mg/dL experienced no significant changes in HDL cholesterol or triglyceride level with treatment.

Regardless of baseline triglyceride level, the researchers report, gemcabene at higher doses (600- and 900-mg daily doses) significantly reduced serum LDL cholesterol, apolipoprotein B, and non-HDL cholesterol levels.

Adverse event profiles were similar for gemcabene and placebo, the investigators report, and all dose regimens of gemcabene were well tolerated.

"An intriguing result of this trial is the potential benefit that gemcabene may have in patients with elevated non-HDL cholesterol," the authors conclude. "Due to the inclusion of more atherogenic particles, some studies have suggested that non-HDL cholesterol may be a better predictor of coronary heart disease risk than LDL cholesterol alone." Am J Cardiol 2003;92:538-543.