Flushing Profile of Extended-Release Niacin/Laropiprant at Initiation of Therapy in Asian Lipid Clinic Patients

Abstract

Objective: Niacin is underutilized due to flushing, which occurs in over 90% of niacin-treated patients. Laropiprant (LRPT) reduces flushing associated with niacin. This study compared flushing with a combination tablet of extended-release (ER) niacin (ERN)/LRPT to niacin ER (N-ER; without LRPT) during the first week of therapy among patients in Asia. Methods: Following a 1-week placebo run-in, 332 patients with dyslipidemia from China, Korea and Singapore were randomized to ERN/LRPT 1 g/20 mg, N-ER 1 g (given as Niaspan®) or placebo in a 2:2:1 ratio for 1 week. Patient-reported flushing severity was assessed using the Global Flushing Severity Score (GFSS; none/mild = 0–3; moderate = 4–6; severe = 7–9; extreme = 10). Results: Compared with N-ER, the ERN/LRPT group experienced significantly less flushing (p < 0.001), as measured by maximum GFSS categorized as none/mild, moderate, severe or extreme. Overall, 23.8% of patients in the ERN/LRPT group and 50.0% in the N-ER group (p < 0.001), versus 12.1% in the placebo group, had moderate or greater flushing (GFSS ≥4). Except for flushing, which occurred more frequently in the N-ER group, ERN/LRPT had a safety/tolerability profile similar to that of N-ER. Conclusion: ERN/LRPT produced significantly less flushing than N-ER during the initiation of therapy and was generally well tolerated in Asian patients with dyslipidemia.

Extended Release Niacin-Laropiprant in Patients with Hypercholesterolemia or Mixed Dyslipidemias Improves Clinical Parameters

“…35.7% of the patients receiving ERN alone discontinued: this is not unexpected and is in line with previous studies assessing the tolerability of this agent (this compared with a dropout rate of 11.5% for the placebo group). However, the dropout rate for the group receiving ERN/laropiprant was still 28.5%, which is conistent with other studies that suggest that the dropout rate due to flushing with laropiprant is still around 25% 9,106,107…”

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

“…By comparison, a 1-week acute study designed specifically to assess the flushing profile of ERN/ LRPT in an Asian population demonstrated significant reductions in the ERN/LRPT group vs the niacin extendedrelease treatment group in treatment-related flushing AEs (9.8% vs 25.4%, respectively) and flushing-related discontinuations (0.8% vs 3.7%, respectively). 17 The flushing efficacy observed in an Asian population 17 were consistent with the results from a large, multinational Phase III clinical trial. 16 Niacin is known to cause increases in liver transaminases (ALT/AST) in some patients and rarely has been associated with clinical hepatotoxicity.…”

“…16 In a study of Asian patients referred to a lipid clinic, ERN/ LRPT produced significantly less flushing than niacin extended-release during the initiation of therapy. 17 The present Phase III, randomized, double-blind study evaluated the lipid-modifying efficacy of ERN/LRPT 2 g given as monotherapy or coadministered with statins in dyslipidemic patients in Asia, bridging the efficacy of ERN/LRPT in Asian patients to the previous efficacy results from a large-scale, multinational study in non-Asian patients. 16 …”

Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed&nbsp; dyslipidemias and primary hypercholesterolemia

“…In a randomized controlled trial which consisted of three arms: placebo, ER niacin, and the combination of ER niacin with laropiprant, the combination lowered LDL-C by 18%, triglycerides by 25% and increased HDL-C by 20%, which was similar to ER niacin only 96. This trial, along with several others,98,99 clearly demonstrated the attenuation of flushing with laropiprant. In this 24-week study the discontinuation due to flushing was 10% in the combination group versus 22% in the ER niacin group without laropiprant, compared to 0.7% in the placebo group 96…”