title: Intra-individual variability in clopidogrel responsiveness in coronary artery disease patients under long term therapy.
abstract: Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic events after percutaneous coronary interventions (PCI). Some of the mechanisms involved in large inter-individual variability in CR may be varied. We therefore postulated that there may be an intra-individual variability in CR. Two hundred and one patients receiving long-term therapy with aspirin and clopidogrel after drug-eluting stents PCI were prospectively included in this monocentre study along with any patient re-admitted within 12 months post-PCI. Platelet reactivity (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index following a 600 mg loading dose of clopidogrel on each admission to determine CR (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP = VASP 2 &#x2013;VASP 1 was used to study intra-individual variability in CR. We observed that the response to a 600 mg LD of clopidogrel was poorly correlated within an individual (kappa = 0.33; p &lt; 0.001 (n = 201)). Although most patients had increased platelet inhibition at the time of readmission, 35.3% of patients exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin-treated diabetes was associated with decreased CR over time (p = 0.03). In addition to the large inter-individual variability in clopidogrel responsiveness, there is large intra-individual variability. Decreased clopidogrel responsiveness despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic events.
authors.affiliation: Pôle de Cardiologie, Service de Cardiologie Interventionnelle, Hôpital Universitaire Nord, AP-HM, Faculté de Médecine, Université Aix-Marseille II, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Arméro
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin Jau
authors.forename: Omar
authors.initials: O
authors.lastname: Omar Aït Mokhtar
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.forename: Caroline
authors.initials: C
authors.lastname: Burignat-Bonello
authors.forename: Iliassou
authors.initials: I
authors.lastname: Tahirou
authors.forename: Stéphane
authors.initials: S
authors.lastname: Arques
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
mesh_terms: D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D054855:Drug-Eluting Stents; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin