The effects of statin monotherapy and low-dose statin/ezetimibe on lipoprotein-associated phospholipase A₂

Clin Cardiol. 2011 Feb;34(2):108-12. doi: 10.1002/clc.20853.

Abstract

Background: Many of the pleiotropic effects of statins remain to be elucidated.

Hypothesis: Different statin regimens with similar lipid-lowering efficacy may have different effects on biomarkers of atherothrombosis including lipoprotein-associated phospholipase A₂ (Lp-PLA₂ ).

Methods: After a 4-week dietary lead-in, 82 hypercholesterolemic patients were randomized to 1 of 2 treatment groups: atorvastatin 20 mg or atorvastatin/ezetimibe 5 mg/5 mg. After 8 weeks of drug treatment, the groups were compared for percent change in lipid parameters, Lp-PLA₂ , interleukin-6 (IL-6), monocyte chemoattractant protein-1, and fibrinogen.

Results: Low-density lipoprotein cholesterol (LDL-C) lowering was comparable between the 2 groups (-47% ± 11% and -49% ± 7% in the atorvastatin and combination groups, respectively). Although Lp-PLA₂ was reduced in both groups, the reduction was greater in the atorvastatin group (-42% and -9% [median], respectively, P = 0.03). Although IL-6 was decreased only in the atorvastatin group, IL-6 changes were not significantly different between the 2 groups. The changes in monocyte chemoattractant protein-1 and fibrinogen were similar in each group.

Conclusions: Atorvastatin monotherapy was stronger at reducing plasma Lp-PLA₂ than the low-dose atorvastatin/ezetimibe combination after equivalent LDL-C lowering. This result may provide evidence of potential statin effects beyond the lowering of LDL-C.

Publication types

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

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood*
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / drug effects
  • Adult
  • Aged
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Azetidines / administration & dosage
  • Azetidines / therapeutic use*
  • Biomarkers, Pharmacological / blood
  • Chemokine CCL2 / metabolism
  • Cholesterol, LDL / blood
  • Drug Therapy, Combination
  • Ezetimibe
  • Female
  • Fibrinogen / metabolism
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Biomarkers, Pharmacological
  • CCL2 protein, human
  • Chemokine CCL2
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-6
  • Pyrroles
  • Fibrinogen
  • Atorvastatin
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Ezetimibe