Short-term effects of extended-release niacin with and without the addition of laropiprant on endothelial function in individuals with low HDL-C: a randomized, controlled crossover trial.
BACKGROUND
Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation.


OBJECTIVE
This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C.


METHODS
Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2.


RESULTS
Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD.


CONCLUSIONS
In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil.
Valeria
V
Nasser Figueiredo
Lipids Laboratory, State University of Campinas Medical School, São Paulo, Brazil.
Felipe
F
Vendrame
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil.
Bruno A
BA
Colontoni
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil.
Thiago
T
Quinaglia
Department of Internal Medicine, State University of Campinas Medical School, São Paulo, Brazil.
Jose
J
Roberto Matos-Souza
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil.
Filipe
F
Azevedo Moura
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil.
Otavio R
OR
Coelho
Lipids Laboratory, State University of Campinas Medical School, São Paulo, Brazil.
Eliana C
EC
de Faria
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil. Electronic address: andreisposito@gmail.com.
Andrei C
AC
Sposito
D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D014665:Vasodilator Agents; D009525:Niacin
HDL; endothelial function; laropiprant; niacin