title: Does the response to aspirin and clopidogrel vary over 6 months in patients with ischemic heart disease?
abstract: BACKGROUND
  Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, mostly clopidogrel, is the default therapy in both acute coronary syndrome (ACS) and after intracoronary stents. It is well established that responses to antiplatelet therapy (APT), particularly clopidogrel, are subject to considerable interindividual variability.
  
  
  OBJECTIVE
  We investigated whether responses to APT in individuals vary significantly over time.
  
  
  METHODS
  Simultaneous assay with VerifyNow(™) and short thrombelastography (s-TEG) was performed before and at four time points over 6 months after hospital discharge in 40 patients receiving DAPT. Serum thromboxane B2 levels were also measured.
  
  
  RESULTS
  While aspirin response units (ARU) by VerifyNow(™) and serum thromboxane B2 levels remained stable over time, arachidonic acid (AA)-mediated platelet aggregation with s-TEG (i.e. area under the curve at 15 min in AA channel, AUC15AA ) increased at 1 week compared with predischarge (P < 0.008). In addition, platelet reactivity units (PRU) by VerifyNow(™) (P = 0.046) and adenosine diphosphate (ADP)-mediated platelet aggregation with s-TEG (i.e. AUC15ADP ) also increased at 1 week compared with predischarge (P = 0.026). There were no significant changes in either platelet reactivity or rates of high on-treatment platelet reactivity while receiving clopidogrel beyond 1 week.
  
  
  CONCLUSIONS
  This study demonstrates important variability in responses to APT within individuals between predischarge and 1 week but not thereafter. The use of a single early (predischarge) platelet function assay as an indicator of future response may therefore be flawed. The design of future strategies to assess individual responses for tailored therapy needs to take this into account.
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Faculty of Medicine, University of Southampton, Southampton, UK.
authors: V
authors: http://orcid.org/0000-0002-8597-6584
authors: V
authors: Khanna
authors: Faculty of Medicine, University of Southampton, Southampton, UK.
authors: R
authors: R
authors: Mikael
authors: Faculty of Medicine, University of Southampton, Southampton, UK.
authors: K
authors: K
authors: Thayalasamy
authors: Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
authors: N
authors: N
authors: Sambu
authors: Faculty of Medicine, University of Southampton, Southampton, UK.
authors: B D
authors: BD
authors: Dimitrov
authors: Faculty of Medicine, University of Southampton, Southampton, UK.
authors: N
authors: N
authors: Englyst
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors: A L
authors: AL
authors: Calver
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors: S
authors: S
authors: Corbett
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors: H
authors: H
authors: Gray
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors: I A
authors: IA
authors: Simpson
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors: J R
authors: JR
authors: Wilkinson
authors: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Faculty of Medicine, University of Southampton, Southampton, UK.
authors: N
authors: N
authors: Curzen
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004739:England; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D015203:Reproducibility of Results; D013916:Thrombelastography; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013929:Thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: aspirin; clopidogrel; platelet aggregation; platelet function tests; thrombelastography