Joseph M. Keenan
University of Minnesota, USA
Dr. Joseph M. Keenan is a professor at University of Minnesota, USA.
Background: Nicotinic acid (NA), long used for the treatment of dyslipidemia, has shown problems with undesirable side eff ects and safety issues. Wax-matrix, extended-release niacin (WMER) and inositol hexanicotinate (IHN) have both been formulated to increase patient tolerability. Several trials of WMER demonstrated good effi cacy in improving dyslipidemia; however, there are few scientifi c data on the use of IHN. Objective: Th is study was designed to compare the effi cacy and tolerability of WMER and IHN to each other and placebo to help clinicians make an informed choice of NA agents. Methods: Th is was a 6-week blinded, placebo-controlled trial comparing 1500 mg/d of WMER with 1500 mg/d IHN. Subjects with mild-to-moderate dyslipidemia (low-density lipoprotein 130- 190/dL) were randomized, aft er a 4-week diet lead-in period, to three parallel study arms (40 subjects/ arm). Diet, pill compliance, and side eff ects were monitored as well as lipid and blood chemistry profi les (baseline, 6 weeks). A dose-reduction protocol was included for subjects who did not tolerate the 1500-mg dose of NA. A pharmacokinetic substudy was conducted on subjects from the WMER (n=5) and IHN (n=5) groups. Results: WMER demonstrated signifi cant improvements in total cholesterol-11%, lowdensity lipoprotein-18%, highdensity lipoprotein+12%, and non-high-density lipoprotein-15% (P<0.001), whereas IHN and placebo showed no signifi cant improvement in lipids. All groups had good medication compliance and treatment tolerance with only one dropout in the WMER group as the result of fl ushing. Blood chemistries showed small (24%-27%) mean increases in hepatic transaminases; six subjects completed the study at reduced dosage protocol with good lipid results. Pharmacokinetics demonstrated an intermediate release and absorption rate for WMER over 6 hours and IHN showed no evidence of bioavailability. Conclusion: WMER demonstrated good tolerance and effi cacy and extended-release kinetics. IHN was well tolerated but was no better than placebo in lipid improvement and showed no evidence of bioavailability.