Abstract 191: Flushing Profile of ER Niacin/Laropiprant in Patients with Primary Hypercholesterolemia or Mixed Dyslipidemia
PURPOSE: Niacin is underutilized due to prostaglandin D2 (PGD2)-mediated flushing. Laropiprant (LRPT) is a PGD2 receptor antagonist that reduces flushing associated with extended release niacin (ERN). This Phase III double-blind study evaluated flushing and lipid efficacy of a combination tablet of ERN/LRPT.
METHODS: 1613 dyslipidemic patients (pts), 66% of whom were receiving statin treatment, were randomized 3:2:1 to ERN/LRPT 1 g/20 mg, ERN 1 g, or placebo (PBO). After 4 wks, doses were doubled (ERN/LRPT =2 g/40 mg as 2 1g /20 mg tablets) for 20 additional wks. Effects of ERN/LRPT vs ERN on patient-reported flushing severity during therapy initiation (Wk 1) and maintenance (Wks 2–24) were assessed using a validated Global Flushing Severity Score, which patients completed using a daily eDiary.
RESULTS: Pts on ERN/LRPT reported significantly lower flushing intensity during Wk 1 compared to ERN alone (p<0.001). During Wks 2–24, pts on ERN/LRPT had less flushing as measured by (1) % of patients and (2) days/week with “moderate or greater” flushing vs pts taking ERN (Figure⇓). More ERN pts (22%) discontinued due to flushing than ERN/LRPT pts (10%). Relative to PBO, ERN/LRPT 2 g produced significant (p<0.001) LS mean changes in LDL-C (− 18.4%), triglycerides (− 25.8%), non-HDL-C (− 19.8%), apolipoprotein (Apo) B (− 18.8%), HDL-C (18.9%) and Apo A-I (6.9%).
CONCLUSIONS: The improved flushing profile of ERN/LRPT vs ERN, with robust lipid efficacy, supports a simplified 1 g →2 g 4-wk dose escalation regimen and should allow more pts to effectively reach and maintain a 2 g dose of niacin, a therapy proven to reduce cardiovascular risk.