Lipid-modifying efficacy of extended release niacin/laropiprant in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia

Background

Niacin has proven lipid-modifying efficacy and cardiovascular benefit; however, it is underused because of skin flushing, a process mediated primarily by prostaglandin D₂ (PGD₂). Laropiprant (LRPT), a PGD₂ receptor (DP1) antagonist that mitigates niacin-induced flushing, has been combined with extended-release niacin (ERN) into a fixed-dose tablet containing 1g of ERN and 20mg of LRPT (ERN/LRPT 1g). In a large-scale (n=∼1600), multinational, 6-month study in dyslipidemic patients, ERN/LRPT 2g produced superior lipid-modifying efficacy vs placebo, whether administered alone or with concomitant statins.

Objective

This Phase III, randomized, double-blind study evaluated the lipid-modifying efficacy of ERN/LRPT alone or added to ongoing statins in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia.

Methods

After a 4-week placebo run-in, patients were randomized to ERN/LRPT 1g (n=322) or placebo (PBO; n=324). After 4 weeks, the dose was advanced to 2 tablets/d (ERN/LRPT 2g or PBO) for 8 additional weeks. End points included effects of ERN/LRPT 2g vs PBO on low-density lipoprotein cholesterol (LDL-C; primary), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and other lipids/lipoproteins.

Results

Relative to PBO, ERN/LRPT 2g produced significant (P < .001) changes in LDL-C (−14.7%), HDL-C (15.9%), TG (−23.4%), LDL-C:HDL-C (−25.5%), non-HDL-C (−16.4%), apolipoprotein (Apo) B (−15.4%), and Apo A-I (5.3%) from baseline to week 12 in the total population. Similar results were observed in patients treated with ERN/LRPT alone or added to ongoing statin.

Conclusion

ERN/LRPT 2g, administered alone or with a statin, produced significant improvements in multiple lipid/lipoprotein parameters in dyslipidemic Asian patients.

Keywords: Extended-release niacin, Flushing, Laropiprant, Primary hypercholesterolemia, Mixed hyperlipidemia