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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Merck, Whitehouse Station, NJ 07065, USA. fabian.chen.md.phd@gmail.com
Fabian
F
Chen
Darbie
D
Maccubbin
Lizhen
L
Yan
Waheeda
W
Sirah
Erluo
E
Chen
Christine McCrary
CM
Sisk
Michael
M
Davidson
Peder
P
Blomqvist
James M
JM
McKenney
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D007211:Indoles; D008055:Lipids; C518174:MK-0524; D011758:Pyrroles; D009525:Niacin; D000069059:Atorvastatin; D019821:Simvastatin