Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention.
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.
Angiolillo
Dominick J
DJ
Division of Cardiology, University of Florida-Shands Jacksonville, Jacksonville, Florida, USA. dominick.angiolillo@jax.ufl.edu
Fernandez-Ortiz
Antonio
A
Bernardo
Esther
E
Ramírez
Celia
C
Sabaté
Manel
M
Jimenez-Quevedo
Pilar
P
Hernández
Rosana
R
Moreno
Raul
R
Escaned
Javier
J
Alfonso
Fernando
F
Bañuelos
Camino
C
Costa
Marco A
MA
Bass
Theodore A
TA
Macaya
Carlos
C
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
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