A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extended-release and lovastatin.
BACKGROUND
Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders, especially those at high risk.


OBJECTIVE
This study evaluated dose-response relationships and safety of a new dual-component drug product containing niacin extended-release (niacin ER) and lovastatin.


METHODS
The 28-week double-blind multicenter trial randomized 237 patients with type IIA or IIB hyperlipidemia to one of four escalating-dose treatment groups: niacin ER/lovastatin 1,000/20 mg, niacin ER/lovastatin 2,000/40 mg, niacin ER 2,000 mg, or lovastatin 40 mg.


RESULTS
Niacin ER/lovastatin was more effective than each of its components for improving levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), and exhibited a clear dose-response effect and additivity across the dosage range. The 2,000/40 dose achieved greater mean reductions in LDL-C (-42%) than 1,000/20 (-28%, p < 0.001), lovastatin 40 mg (-32%, p < 0.05), or niacin ER 2,000 mg (-14%, p < 0.05). The 2,000/40 dose was significantly more effective in increasing HDL-C levels (+30%) than the 1,000/20 dose (+21%, p = 0.016). The decrease in TG was greater with 2,000/40 (-43%) than with 1,000/20 (-26%, p = 0.009). All three niacin-containing treatments were more effective than lovastatin monotherapy in reducing lipoprotein (a) [Lp(a)] levels. Flushing caused 12 (11%) patients receiving niacin ER/lovastatin and I patient receiving lovastatin alone to withdraw. No drug-related myopathy was noted. One patient each in the 2,000/40 group and the lovastatin 40-mg group had reversible elevations in liver transaminases.


CONCLUSIONS
Niacin ER/lovastatin is well tolerated and effective for patients with multiple lipid disorders.
Hunninghake
Donald B
DB
The Heart Disease Prevention Clinic, University of Minnesota, Minneapolis, Minnesota 55455, USA. hunni001@maroon.tc.umn.edu
McGovern
Mark E
ME
Koren
Michael
M
Brazg
Ronald
R
Murdock
David
D
Weiss
Stuart
S
Pearson
Thomas
T
D000704:Analysis of Variance; D016009:Chi-Square Distribution; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis* / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008148:Lovastatin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D011336:Probability; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D004338:Drug Combinations; D000960:Hypolipidemic Agents; D009525:Niacin; D008148:Lovastatin