Abstract 12811: Lipid-Altering Efficacy and Safety Profile of Co-Administered Extended Release Niacin/Laropiprant and Simvastatin Versus Atorvastatin in Patients With Mixed Hyperlipidemia
Purpose: Co-administered niacin and statin offers comprehensive lipid management, but is underutilized due to niacin-induced flushing. A tablet containing extended-release niacin and laropiprant (ERN/LRPT) reduces flushing, while preserving the lipid-modifying effects of ERN. This Phase III study assessed the efficacy and safety of ERN/LRPT co-administered with simvastatin (ERN/LRPT + SIMVA) vs atorvastatin (ATORVA) in patients with mixed hyperlipidemia.
Methods: After a 4-week placebo run-in, 2340 patients with mixed hyperlipidemia (LDL-C ≥130 and ≤190 mg/dL; TG ≥150 and ≤500 mg/dL) and above NCEP ATP III LDL-C goal were randomized to 1 of 6 treatment groups: ERN/LRPT 2 g/20 mg + SIMVA (20 or 40 mg) or ATORVA (10, 20, 40 or 80 mg) once-daily for 12 weeks. Endpoints included changes from baseline to week 12 in LDL-C:HDL-C (primary) and HDL-C, TG, non-HDL-C and LDL-C (key secondary) for ERN/LRPT + SIMVA vs ATORVA.
Results: At week 12, ERN/LRPT + SIMVA was superior to ATORVA in decreasing LDL-C:HDL-C, increasing HDL-C and reducing TG for all pre-specified dose comparisons and in reducing non-HDL-C and LDL-C for ERN/LRPT + SIMVA 20 mg vs ATORVA 10 mg and ERN/LRPT + SIMVA 40 mg vs ATORVA 20 mg, but not ERN/LRPT + SIMVA 40 mg vs ATORVA 40 mg and ATORVA 80 mg (Table). ERN/LRPT + SIMVA had a similar safety profile to ATORVA, except for AEs related to flushing (21.7% vs 3%; p<0.001) and new-onset diabetes (0.9% vs 0.2%; p=0.023). A lower incidence of consecutive ALT/AST elevations ≥3x ULN was observed with ERN/LRPT + SIMVA (pooled) vs ATORVA (pooled) (0.4% vs 1.8%; p=0.008).
Conclusions: ERN/LRPT + SIMVA was superior to ATORVA in decreasing LDL-C:HDL-C, increasing HDL-C and reducing TG after 12 weeks and was generally well-tolerated in patients with mixed hyperlipidemia.
- © 2011 by American Heart Association, Inc.