Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia

BackgroundExtended-release niacin/laropiprant (ERN/LRPT) reduces flushing and preserves the lipid-modifying effects of ERN. This study compared the efficacy and safety of ERN/LRPT plus simvastatin (ERN/LRPT + SIMVA) with atorvastatin (ATORVA) in patients with mixed hyperlipidemia.MethodsAfter a 4-week placebo run-in, 2340 patients (LDL-C ≥ 130 and ≤ 190 mg/dL, TG ≥ 150 and ≤ 500 mg/dL and above NCEP ATP III risk-based LDL-C goal) were randomized to 1 of 6 treatment arms: ERN/LRPT 1 g/20 mg + SIMVA (10 or 20 mg), or ATORVA (10, 20, 40, or 80 mg) once daily.ResultsAt Week 12, ERN/LRPT + SIMVA was superior to ATORVA in decreasing LDL-C/HDL-C (primary endpoint) at each pre-specified dose comparison: ERN/LRPT + SIMVA 20 mg vs. ATORVA 10 mg (− 13.2%; p < 0.001); ERN/LRPT + SIMVA 40 mg vs. ATORVA 20 mg (− 10.8%; p < 0.001); ATORVA 40 mg (− 5.1%; p < 0.001); and ATORVA 80 mg (− 4.2%; p = 0.007). At Week 12, ERN/LRPT + SIMVA was superior to ATORVA in increasing HDL-C and reducing TG for all pre-specified treatment comparisons, and reducing non-HDL-C and LDL-C for the ERN/LRPT + SIMVA 20 mg versus ATORVA 10 mg and ERN/LRPT + SIMVA 40 mg versus ATORVA 20-mg dose comparisons, but not the ERN/LRPT + SIMVA 40 mg versus ATORVA 40- and 80-mg dose comparisons. Adverse experiences (AEs) typically associated with niacin (flushing, pruritus, increased glucose, increased uric acid) were more common with ERN/LRPT + SIMVA, and hepatic-related laboratory AEs were more common with ATORVA.ConclusionERN/LRPT + SIMVA was generally superior to ATORVA in improving lipid parameters after 12 weeks and was generally well tolerated in patients with mixed hyperlipidemia.