Abstract 683: Lipid-Altering Efficacy and Safety Profile of Co-administered Extended Release Niacin/Laropiprant and Simvastatin in Patients with Dyslipidemia
Objectives: Large intervention studies suggest that while lowering LDL-C is beneficial, it is insufficient to prevent the majority of CHD events. Coadministration of niacin with a statin offers the potential for additional lipid management, but sustained use of niacin is limited due to flushing, mediated by prostaglandin D2 (PGD2). A combination tablet containing 1 g of extended-release niacin and 20 mg of laropiprant (ERN/LRPT), a PGD2 receptor antagonist, offers improved tolerability, supporting a simplified 1 g → 2 g dosing regimen and improved adherence. This Phase III factorial study assessed the efficacy and safety of ERN/LRPT (2 g/40 mg) coadministered with simvastatin (ERN/LRPT + SIMVA) in patients (pts) with primary hypercholesterolemia or mixed dyslipidemia.
Methods: After a 6- to 8-wk washout and 4-wk diet/placebo run-in, 1398 pts were randomized equally to ERN/LRPT 1 g/20 mg, SIMVA (10, 20, or 40 mg), or ERN/LRPT 1 g/20 mg + SIMVA (10, 20, or 40 mg) once-daily for 4 wks. At Wk 5, all doses were doubled except SIMVA 40 mg (unchanged) and ERN/LRPT 1 g/20 mg + SIMVA 40 mg (switched to ERN/LRPT 2 g/40 mg + SIMVA 40 mg) for 8 wks. The primary endpoint was mean % change from baseline to Wk 12 in LDL-C for ERN/LRPT + SIMVA (pooled across SIMVA doses) vs. ERN/LRPT. Secondary endpoints included changes in TG, HDL-C, non-HDL-C and apo B.
Results: ERN/LRPT + SIMVA (pooled across doses) significantly improved all lipid parameters compared with ERN/LRPT alone and pooled SIMVA alone (Table⇓). At each dose, ERN/LRPT + SIMVA significantly improved lipids compared to the corresponding SIMVA dose. ERN/LRPT + SIMVA was generally well tolerated with a safety profile similar to ERN/LRPT alone.
Conclusions: ERN/LRPT + SIMVA significantly improved the overall lipid profile and was generally well tolerated in pts with dyslipidemia. These data support the use of LRPT to improve the tolerability and therapeutic dosing of niacin, alone and with a statin-therapies proven to reduce cardiovascular risk.