title: Clopidogrel withdrawal is associated with proinflammatory and prothrombotic effects in patients with diabetes and coronary artery disease.
abstract: Inhibition of the P2Y12 pathway by the platelet antagonist clopidogrel is associated with a marked reduction in platelet reactivity. Recent reports have shown that P2Y12 inhibition has anti-inflammatory effects as well. However, whether clopidogrel withdrawal is associated with proaggregatory and proinflammatory effects has not yet been explored. Since diabetic subjects are characterized by a prothrombotic and proinflammatory status, we hypothesize that these patients may be more vulnerable to these effects. A total 54 patients with diabetes on long-term (12 months) dual antiplatelet therapy (aspirin plus clopidogrel) were studied. Platelet aggregation (following 6 and 20 micromol/l ADP stimuli) and inflammatory markers (C-reactive protein and P-selectin expression) were assessed before and 1 month following clopidogrel withdrawal. Following clopidogrel withdrawal, aspirin responsiveness using platelet function analyzer-100 was determined as well. A significant increase in all the assessed platelet (P < 0.0001 for 6 and 20 micromol/l ADP-induced aggregation) and inflammatory (P < 0.05 for C-reactive protein, P < 0.001 for P-selectin expression in resting platelets, and P < 0.0001 for P-selectin expression in ADP-stimulated platelets) biomarkers was observed following clopidogrel withdrawal. Low responders to aspirin had increased platelet aggregation profiles (P < 0.05 for 6 and 20 micromol/l ADP-induced aggregation) but no differences in inflammatory markers. In conclusion, clopidogrel withdrawal is associated with an increase in platelet and inflammatory biomarkers in diabetic patients, supporting pleiotropic effects coupled with P2Y12 receptor antagonism.
authors.affiliation: Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th St., Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Ortiz
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.forename: Celia
authors.initials: C
authors.lastname: Ramírez
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: Pilar
authors.initials: P
authors.lastname: Jimenez-Quevedo
authors.forename: Rosana
authors.initials: R
authors.lastname: Hernández
authors.forename: Raul
authors.initials: R
authors.lastname: Moreno
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.forename: Camino
authors.initials: C
authors.lastname: Bañuelos
authors.forename: Marco A
authors.initials: MA
authors.lastname: Costa
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D048909:Diabetes Complications / Q000209:etiology; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome / Q000097:blood*; D013927:Thrombosis / Q000209:etiology*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin