Baseline lipoprotein lipids and low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl ester added to Simvastatin therapy

Am J Cardiol. 2010 May 15;105(10):1409-12. doi: 10.1016/j.amjcard.2009.12.063. Epub 2010 Mar 30.


The present post hoc analysis of data from the COMBination of prescription Omega-3 with Simvastatin (COMBOS) study investigated the predictors of the low-density lipoprotein (LDL) cholesterol response to prescription omega-3 acid ethyl ester (P-OM3) therapy in men and women with high (200 to 499 mg/dl) triglycerides during diet plus simvastatin therapy. Subjects (n = 256 randomized) received double-blind P-OM3 4 g/day or placebo for 8 weeks combined with diet and open-label simvastatin 40 mg/day. The percentage of changes from baseline (with diet plus simvastatin) in lipids was evaluated by tertiles of baseline LDL cholesterol and triglyceride concentrations. The baseline LDL cholesterol tertile was a significant predictor of the LDL cholesterol response (p = 0.022 for the treatment by baseline tertile interaction). The median LDL cholesterol response in the P-OM3 group was +9.5% (first tertile, <80.4 mg/dl), -0.9% (second tertile), and -6.4% (third tertile, > or =99.0 mg/dl). Non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride responses did not vary significantly by baseline LDL cholesterol tertile. The reductions in very-low-density lipoprotein cholesterol concentrations were greater than the increases in LDL cholesterol, where present, resulting in a net decrease in the concentration of cholesterol carried by atherogenic particles (non-high-density lipoprotein cholesterol) in all baseline LDL cholesterol tertiles. In conclusion, these results suggest that the increase in LDL cholesterol that occurred with the addition of P-OM3 to simvastatin therapy in subjects with mixed dyslipidemia was confined predominantly to those with low LDL cholesterol levels while receiving simvastatin monotherapy.

Trial registration: NCT00246701.

Publication types

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

MeSH terms

  • Aged
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperlipidemias / blood
  • Hyperlipidemias / diagnosis
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / administration & dosage
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Probability
  • Risk Assessment
  • Severity of Illness Index
  • Simvastatin / administration & dosage*
  • Treatment Outcome


  • Cholesterol, LDL
  • Fatty Acids, Omega-3
  • Hypolipidemic Agents
  • Simvastatin

Associated data