Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting: results from the CLEAR PLATELETS 1b study

J Am Coll Cardiol. 2006 Dec 5;48(11):2186-91. doi: 10.1016/j.jacc.2005.12.084.

Abstract

Objectives: This study was performed to compare the effects of antiplatelet regimens on early inflammation and cardiac marker release after elective stenting.

Background: Few data exist regarding the comparative effects of specific antiplatelet regimens on early inflammation marker release after stenting.

Methods: In a 2 x 2 factorial randomized investigation, patients undergoing stenting were treated with either clopidogrel alone (300 mg or 600 mg; n = 60) or clopidogrel with eptifibatide (n = 60). Platelet aggregation (5 and 20 muM adenosine diphosphate [ADP]), ADP-stimulated expression of active glycoprotein (GP) IIb/IIIa, and platelet-bound P-selectin, tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), and cardiac markers were measured.

Results: Compared with a strategy of clopidogrel alone, clopidogrel + eptifibatide reduced the release of cardiac markers. A marked reduction in platelet aggregation and active GP IIb/IIIa expression (p < or = 0.001) with clopidogrel + eptifibatide was associated with a decrease in CRP and TNF-alpha release (p < or = 0.001).

Conclusions: A strategy of clopidogrel with GP IIb/IIIa blockade resulted in superior inhibition of inflammation and cardiac marker release, which was accompanied by superior platelet inhibition immediately after percutaneous coronary intervention compared with a strategy of clopidogrel alone. The mechanistic and clinical implications of attenuated periprocedural inflammation and myocardial necrosis with a strategy of GP IIb/IIIa inhibition warrant further investigation.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Platelets / drug effects
  • C-Reactive Protein / metabolism*
  • Clopidogrel
  • Creatine Kinase, MB Form / blood
  • Eptifibatide
  • Female
  • Flow Cytometry
  • Humans
  • Inflammation / metabolism
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / therapy*
  • Myocardium / pathology
  • Necrosis
  • P-Selectin / blood
  • Peptides / therapeutic use*
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Stents*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Biomarkers
  • P-Selectin
  • Peptides
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Clopidogrel
  • Creatine Kinase, MB Form
  • Eptifibatide
  • Ticlopidine