Abstract 188: The Safety and Efficacy of a Combination of Extended-Release Niacin and Simvastatin in Patients With Dyslipidemia (SEACOAST): A Dose-Ranging Study
Introduction: Combining niacin with a statin provides beneficial effects on a broad range of lipid particles, further reducing CV risk when compared with statins. This 24-week RCT compared simvastatin (S) to a novel combination of extended-release niacin with S (NS) in patients (Pts) with elevated non-HDL-C (type II hyperlipidemia or mixed dyslipidemia).
Methods: Following an S run-in phase (variable dose), Pts were assigned to either an S low-dose (SLD; 20 mg S) or an S high-dose (SHD; 80 mg S) group based on final run-in S dose. Pts in SLD were randomized to NS 2000/20, NS 1000/20, or S 20, while Pts in SHD were randomized to NS 2000/40, NS 1000/40 or S 80. S control groups received 50 mg niacin IR to maintain blinding. Target NS dose was attained by Week 12. The primary endpoint was median % change from baseline to Week 24 in non-HDL-C.
Results: For SLD, NS demonstrated dose-related improvements in all lipid parameters (Table⇓). For SHD, both NS doses with 40 mg S were non-inferior (comparable) to S 80 in non-HDL-C reduction while demonstrating dose-related improvements in HDL-C, Lp(a) and TG. Treatment-related AEs (TRAEs) occurred in 30% and 24% of Pts receiving NS (n = 403) and S (n = 238), respectively; discontinuation due to a TRAE occurred in 12.4% and 5.5% of Pts. Serious TRAEs occurred in 0.2% and 0.8% of Pts. Flushing occurred in 59% and 47% of Pts; 6% and 0.8% of Pts discontinued due to flushing. No Pt had consecutive AST or ALT >3X upper limit of normal (ULN); 1 Pt (S 80) had CK >10X ULN.
Conclusion: NS demonstrated dose-dependent improvements in lipids. In the SLD group, NS improved all lipid parameters compared with the same S dose (S 20). In the SHD group, both NS doses resulted in similar improvements in non-HDL-C and LDL-C, and significantly greater improvements in HDL-C, Lp(a) and TG, compared with double the S dose (S 80). Treatment with 4 different doses of NS for 24 weeks was well tolerated with no unexpected AEs. There was no evidence for increased risk of hepatotoxicity or myopathy with NS.