Extended-Release Nicotinic Acid Versus Inositol Hexanicotinate for the Treatment of Dyslipidemia

Abstract

Synopsis: This was a comparison of the efficacy, safety, and tolerability of two forms of nicotinic acid (NA), wax-matrix, extended release, nicotinic acid (WMNA), and Inositol Hexanicotinate (IHN), or “no flush” niacin in persons with dyslipidemia. Purpose: To test and compare the tolerability, efficacy and pharmacokinetics of “no flush” IHN and WMNA. Methods: This was a 6-week, 3 parallel arm (n = 120, 40 subjects per arm), double-blind, randomized clinical trial that used 1500 mg/d (500 mg three times a day with meals) of WMNA, IHN, and placebo. Inclusion criteria were baseline lipid levels of LDL (130–190 mg%); high-density lipoprotein (HDL) <60 mg% and triglycerides (TG) < 400 mg%. Subjects were randomized to the three treatment groups. Subjects had fasting lipids, chemistries (glucose, liver function tests, uric acid and homocysteine), and side-effect questionnaire at baseline, end of week 3, and at the end of the study. Results: WMNA demonstrated efficacy in 3 blood lipids (TC = −11%, (P < .001); low-density lipoprotein (LDL) = −18%, (P < .001), and HDL = + 12% (P < .001), but TG results were not significant (−9%, P = .074). Lipid results for IHN (TC = −1%; LDL = −1%; HDL = +1%; TG = +2%) and placebo (TC = 0%; LDL = 0%; HDL = +2% ; TG = −1%) were not significant. All treatments were well tolerated; only one dropout from the WMNA group was attributable to side effects. Compliance with treatment was good; more than 92% of the treatment doses for all groups and dietary compliance (3-day food records) was good. The WMNA group did show a slight increase in blood glucose, homocystiene, and liver enzyme levels, but levels stayed within the range of normal. A five-person subgroup of the WMNA and IHN subjects had a pharmacokinetic study performed in which blood levels of nicotinic acid and metabolites (nicotinamide, nicotinuric acid) were measured over 8 hours after a 500-mg dose of WMNA and IHN. These kinetics demonstrated good extended release of nicotinic acid over the 8 hours in the WMNA group, but the IHN group demonstrated no evidence of nicotinic acid or metabolites in the blood. Conclusions: WMNA is a beneficial and well-tolerated intervention for dyslipidemia. IHN was well tolerated but appears to be virtually nonbioavailable and no better than placebo for the management of dyslipidemia.