title: Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention.
abstract: Increased platelet inhibition is achieved when clopidogrel is added to aspirin (acetylsalicylic acid [ASA]). A broad variability in platelet inhibition profiles during the early phases of treatment has been demonstrated and may be attributed to ASA resistance. However, the influence of ASA sensitivity on platelet function profiles of patients on long-term dual antiplatelet therapy has yet to be explored. A total of 135 patients who had previously undergone percutaneous coronary intervention on long-term (>1 month) ASA and clopidogrel therapy was included. The PFA-100 system was used to define ASA resistance. Platelet aggregation, after adenosine diphosphate (6 and 20 micromol/L) and collagen (6 microg/ml) stimuli, and platelet activation (glycoprotein IIb/IIIa activation and P-selectin expression), after adenosine diphosphate (2 micromol/L) and thrombin receptor-activating peptide (50 micromol/L) stimuli, were assessed by light transmittance aggregometry and flow cytometry, respectively. Patient variability in response to treatment was defined by the coefficient of variability. ASA resistance was found in 60 of 135 patients (44%). Patients with diabetes were more frequently ASA resistant. Collagen/epinephrine- and collagen/adenosine diphosphate-coated cartridges on the PFA-100 had shorter closure times in the ASA-resistant population compared with ASA-sensitive patients. Platelet aggregation and activation were significantly higher in ASA-resistant patients. A broad variability (coefficient of variation >0.25) in patient response to treatment was observed in ASA-resistant and -sensitive patients. In conclusion, ASA resistance is associated with increased platelet reactivity in patients on long-term dual antiplatelet treatment.
authors.affiliation: Division of Cardiology, University of Florida-Shands Jacksonville, Jacksonville, Florida, 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: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D024042:Collagen Type I / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014662:Vasoconstrictor Agents; C086309:thrombin receptor peptide SFLLRNP; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D004837:Epinephrine