Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis.
BACKGROUND
Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol (LDL-C) alone. A new extended-release niacin (niacin ER)/lovastatin tablet substantially lowers LDL-C, triglyceride, and lipoprotein(a) levels and raises high-density lipoprotein cholesterol (HDL-C) level. We evaluated these serum lipid responses to niacin ER/lovastatin at all clinically reasonable doses.


METHODS
Men (n = 85) and women (n = 79) with type IIa or IIb primary hyperlipidemia after diet were randomized among 5 parallel treatment arms. Each arm had 5 sequential 4-week treatment periods: niacin ER (starting at 500 mg/d, increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant lovastatin dose and escalating niacin ER doses.


RESULTS
For primary comparisons, mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin (1500/20 mg) than with lovastatin (20 mg) (35% vs 22%, P<.001) and with niacin ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs 24%, P<.001). Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an additional 4% and increased HDL-C levels 8%. The maximum recommended dose (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%, triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were dose dependent and generally additive. Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses.


CONCLUSIONS
Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease. Dose-response surfaces provide a practical guide for dose selection.
Insull
William
W
Lipid Research Clinic, Baylor College of Medicine and Methodist Hospital, 6560 Fannin Street, Suite 1150, Houston, TX 77030, USA. winsull@tcm
McGovern
Mark E
ME
Schrott
Helmut
H
Thompson
Paul
P
Crouse
J Robin
JR
Zieve
Franklin
F
Corbelli
John
J
D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000188:drug therapy*; D008148:Lovastatin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D009525:Niacin; D008148:Lovastatin