Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis

Arch Intern Med. 2004 May 24;164(10):1121-7. doi: 10.1001/archinte.164.10.1121.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Delayed-Action Preparations / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Lovastatin / administration & dosage*
  • Male
  • Middle Aged
  • Niacin / administration & dosage*
  • Probability
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Niacin
  • Lovastatin