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

Extended-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. After 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 1g/20mg+SIMVA (10 or 20mg), or ATORVA (10, 20, 40, or 80 mg) once daily. At 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 20mg vs. ATORVA 10mg (-13.2%; p<0.001); ERN/LRPT+SIMVA 40 mg vs. ATORVA 20mg (-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 20mg versus ATORVA 10mg 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. ERN/LRPT+SIMVA was generally superior to ATORVA in improving lipid parameters after 12 weeks and was generally well tolerated in patients with mixed hyperlipidemia.

Chen F ，Maccubbin D ，Yan L ，Sirah W ，Chen E ，Sisk CM ，Davidson M ，Blomqvist P ，McKenney JM ... -  《-》

Effects of extended-release niacin/laropiprant, simvastatin, and the combination on correlations between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients with dyslipidemia.

Farnier M ，Chen E ，Johnson-Levonas AO ，McCrary Sisk C ，Mitchel YB ... -  《-》

Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.

Maccubbin D ，Bays HE ，Olsson AG ，Elinoff V ，Elis A ，Mitchel Y ，Sirah W ，Betteridge A ，Reyes R ，Yu Q ，Kuznetsova O ，Sisk CM ，Pasternak RC ，Paolini JF ... -  《-》

Effects of coadministered extended-release niacin/laropiprant and simvastatin on lipoprotein subclasses in patients with dyslipidemia.

The use of extended-release niacin and the prostaglandin D₂ receptor antagonist laropiprant (ERN/LRPT) reduces niacin-induced flushing in patients while preserving its lipid-modifying effects. This predefined exploratory analysis examined the individual and combined effects of ERN/LRPT and simvastatin (SIM) on lipoprotein subclasses. This double-blind study randomized 1398 dyslipidemic patients equally to ERN/LRPT 1 g/20 mg, SIM (10, 20, or 40 mg), or ERN/LRPT 1 g/20 mg + SIM (10, 20, or 40 mg) once daily for 4 weeks. At week 5, doses were doubled, except SIM 40 mg (unchanged) and ERN/LRPT 1 g/20 mg + SIM 40 mg (switched to ERN/LRPT 2 g/40 mg + SIM 40 mg). Cholesterol associated with lipoprotein subclasses was quantified by vertical auto profile II (VAP II). ERN/LRPT + SIM and SIM alone lowered LDL-C 1 and 3, whereas the effects were variable for ERN/LRPT; all three treatments increased LDL-C 4. ERN/LRPT + SIM and ERN/LRPT raised HDL-C 2 and 3, with greater relative percent changes in HDL 2 than HDL 3. ERN/LRPT + SIM for 12 weeks produced substantial reductions in IDL-C, which was additive compared with each monotherapy. Coadministered ERN/LRPT + SIM produced marked reductions in atherogenic lipoproteins, with the greatest effect on IDL-C, and increases in protective HDL subclasses.

Ballantyne C ，Gleim G ，Liu N ，Sisk CM ，Johnson-Levonas AO ，Mitchel Y ... -  《-》

Consistency of extended-release niacin/laropiprant effects on Lp(a), ApoB, non-HDL-C, Apo A1, and ApoB/ApoA1 ratio across patient subgroups.

Bays HE ，Shah A ，Lin J ，Sisk CM ，Dong Q ，Maccubbin D ... -  《-》