A Dose-Ranging Study of a New, Once-Daily, Dual-Component Drug Product Containing Niacin Extended-Release and Lovastatin

Clin Cardiol. 2003 Mar;26(3):112-8. doi: 10.1002/clc.4960260304.

Abstract

Background: Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders, especially those at high risk.

Hypothesis: 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.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Chi-Square Distribution
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperlipidemias / diagnosis*
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / administration & dosage*
  • Lovastatin / administration & dosage*
  • Male
  • Middle Aged
  • Niacin / administration & dosage*
  • Probability
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Drug Combinations
  • Hypolipidemic Agents
  • Niacin
  • Lovastatin