Response to antiplatelet therapy and platelet reactivity to thrombin receptor activating peptide-6 in cardiovascular interventions: Differences between peripheral and coronary angioplasty

Atherosclerosis. 2014 Jan;232(1):119-24. doi: 10.1016/j.atherosclerosis.2013.10.027. Epub 2013 Nov 10.

Abstract

Background: The long-term prognosis of patients with peripheral arterial disease (PAD) is significantly worse than the prognosis of coronary artery disease (CAD) patients. Detrimental platelet activation could contribute to the increased rate of adverse cardiovascular events in PAD. We therefore investigated whether response to antiplatelet therapy and thrombin inducible platelet activation differ between patients with best medical therapy undergoing angioplasty and stenting for symptomatic PAD (n = 166) or CAD (n = 104).

Methods: Adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin receptor activating peptide (TRAP)-6 inducible platelet reactivity was measured by multiple electrode aggregometry (MEA). Platelet surface expression of P-selectin and activated glycoprotein IIb/IIIa (GPIIb/IIIa) in response to ADP, AA, and TRAP-6, and the formation of monocyte-platelet aggregates (MPA) in response to ADP and TRAP-6 were assessed by flow cytometry.

Results: Patients with PAD had significantly higher platelet reactivity in response to ADP and AA by MEA compared to CAD patients. Likewise, the expression of P-selectin and GPIIb/IIIa following stimulation with ADP and AA, and MPA formation in response to ADP were significantly higher in PAD patients than in CAD patients. In response to TRAP-6, patients with PAD showed a significantly increased platelet aggregation by MEA, higher expression of activated GPIIb/IIIa, and more pronounced formation of MPA than CAD patients.

Conclusion: Following angioplasty and stenting, PAD patients exhibit a significantly diminished response to dual antiplatelet therapy and an increased susceptibility to TRAP-6 inducible platelet activation compared to CAD patients.

Keywords: Angioplasty; Coronary artery disease; Peripheral arterial disease; Platelet reactivity.

MeSH terms

  • Adenosine Diphosphate / blood
  • Aged
  • Angioplasty
  • Angioplasty, Balloon, Coronary
  • Arachidonic Acid / blood
  • Aspirin / administration & dosage
  • Blood Platelets / metabolism
  • Cardiovascular Diseases / metabolism*
  • Clopidogrel
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • P-Selectin / metabolism
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism*
  • Percutaneous Coronary Intervention
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / drug therapy*
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemistry*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Prognosis
  • Stents*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives

Substances

  • P-Selectin
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • thrombin receptor peptide (42-47)
  • Arachidonic Acid
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine
  • Aspirin