Extended-release wax-matrix nicotinic acid superior to “flush free” niacin, study shows

Summary

This randomized, double-blind, placebo-controlled trial, completed by University of Minnesota researcher Joseph Keenan, M.D., compares extended-release wax-matrix nicotinic acid (WMNA) to inositol hexanicotinate (IHN), the so-called “flush free” niacin, for the treatment of dyslipidemia. Separately, a sub-study was completed to compare the pharmacokinetics of WMNA and flush free niacin.

For this study, 121 otherwise healthy participants with untreated dyslipidemia were recruited from the university community and surround area. Blood lipids had to indicate eligibility for therapeutic lifestyles changes as outlined in the National Cholesterol Education Program (NCEP) guidelines. Participants met the following blood lipid criteria: HDL-cholesterol no more than (60 mg/dl); LDL-cholesterol no more than 130-190 mg/dl, and triglycerides no more than 400 mg/dl).

One participant decided not to participate before randomization. The remaining 120 participants were randomly assigned to one of three groups: WMNA (1,500 mg/day), IHN (1,500 mg/day), or placebo for 6 weeks.

Instructions were provided for a one-week step-up phase during which participants had the option to take aspirin (325 mg) 30 minutes before the initial daily treatment to reduce flushing and were allowed this option throughout the study. Over the first week, the dose schedule increased from one daily dose (500 mg) at breakfast on Days 1-3, then two daily doses with meals on Days 4-6 and finally three daily doses with meals for the remainder of the study.

Results indicate WMNA significantly (P<.001), improved total cholesterol (-11%), low-density lipoprotein (-18%), high-density lipoprotein (+12%) and non-high-density lipoprotein (-15%). No significant improvements were found with either placebo or IHN. The pharmacokinetic sub-study revealed WMNA had an intermediate release and absorption rate over 6 hours, while IHN showed no evidence of bioavailability.

All groups had good medication compliance and treatment tolerance with only one dropout in the WMNA group as the result of flushing. Six participants in the WMNA group completed the study at reduced dosage protocol (500-1,000 mg/day) with good lipid results (LDL reductions of 22% to 41%; HDL increases of 5% to 37%). Blood chemistries showed small mean increases in hepatic transaminases (24%-27%) and blood glucose (+3%).

The pharmacokinetic sub-study revealed absorption of WMNA was primarily during the first 2-3 hours after ingestion with absorption essential complete within 6 hours. IHN showed no evidence of bioavailability.