Comparison of the efficacy and safety of a combination tablet of niacin extended-release and simvastatin with simvastatin 80 mg monotherapy: the SEACOAST II (high-dose) study.

BACKGROUND

The number of patients with multiple lipid abnormalities is increasing. Lipid treatment guidelines are established for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). The importance of treating HDL-C and triglycerides is gaining recognition.

OBJECTIVE

To determine, in patients who had been treated previously with simvastatin 40 mg/day, the efficacy, safety, and tolerability of two regimens of a combination of proprietary niacin, extended-release core, coated with 40 mg/day simvastatin (NER/S), compared to 80 mg/day simvastatin monotherapy (S80).

METHODS

High-risk patients (n = 343) with dyslipidemia were treated for 24 weeks with NER/S (1000/40 mg/day or 2000/40 mg/day) or S80.

RESULTS

Median percentage change from baseline to week 24 in non-HDL-C in either NER/S group was noninferior to S80 (-11.3%, -17.1%, and -10.1%, respectively). Changes in LDL-C were comparable (-8.6%, -11.6%, and -12.7%, respectively). Doubling the dose of simvastatin (S80) did not alter HDL-C, triglycerides, or lipoprotein(a); however, both NER/S doses resulted in significant improvements in all three parameters (+21.9%, -31.8%, and -21.0%, respectively, for NER/S 2000/40 mg/day). The safety of NER/S was consistent with the safety profile of each individual component. Treatment with both doses of NER/S was well tolerated; 59% of patients experienced flushing, 78% of flushing was mild or moderate in intensity, 49% of those who flushed during dose titration did not flush during weeks 13 to 24, and only 4.6% of patients discontinued because of flushing.

CONCLUSION

NER/S provides similar reductions in non-HDL-C and LDL-C compared to doubling the simvastatin dose to 80 mg; however, only NER/S resulted in improvements in HDL-C, triglycerides, and lipoprotein(a).