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Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study
  1. Nalyaka Sambu1,2,
  2. Hazel Dent2,
  3. Nicola Englyst3,
  4. Timothy D Warner4,
  5. Philip Leadbeater5,
  6. Paul Roderick2,
  7. Huon Gray1,
  8. Iain Simpson1,
  9. Simon Corbett1,
  10. Alison Calver1,
  11. John Morgan1,2,
  12. Nick Curzen1,2
  1. 1Wessex Cardiothoracic Unit, Southampton University Hospital, Southampton, UK
  2. 2School of Medicine, University of Southampton, Southampton, UK
  3. 3Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, UK
  4. 4The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK
  5. 5National Heart and Lung Institute, Imperial College London, London UK
  1. Correspondence to Dr Nick Curzen, Wessex Cardiothoracic Unit, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; nick.curzen{at}


Background The optimal duration of clopidogrel treatment, particularly following drug-eluting stent (DES) implantation, remains contentious. Previous studies have observed a clustering of adverse events following clopidogrel cessation 1 year after DES, the aetiology of which is poorly understood.

Objective To investigate, in the prospective CESSATION study, the effect of clopidogrel withdrawal at 1 year after DES implantation on (i) arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation, and (ii) biomarkers of vascular inflammation, including soluble CD40 ligand (sCD40L), high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6).

Methods and results The prospective CESSATION study was undertaken in 33 patients receiving aspirin and due to discontinue clopidogrel 1 year after DES. Platetet reactivity was measured using short thromboelastography, and compliance with aspirin determined from serum thromboxane B2 (TXB2) levels. Venesection was performed at 4 weeks and 24 h before, and at 24 h, 48 h, 1, 2 and 4 weeks after, clopidogrel cessation. Following clopidogrel withdrawal, there was (i) a predictable increase in ADP-induced platelet aggregation (ii) an unexpected significant increase in AA-induced platelet aggregation (iii) a decline in IL-6 and hsCRP at 1 week and 4 weeks respectively; and (iv) a non-significant increase in sCD40L at 4 weeks TXB2 levels were consistently suppressed, indicating complete inhibition of cyclo-oxygenase-1 by aspirin.

Conclusion An aspirin-independent, time-dependent increase in AA-induced platelet activation following clopidogrel withdrawal in patients with a DES has been described. New insights into a potential mechanism for the observed clustering of adverse events that occur early after clopidogrel cessation have been provided. These findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity.

  • Aspirin
  • clopidogrel cessation
  • drug eluting stent
  • inflammation
  • platelet aggregation
  • coronary artery disease
  • interventional cardiology
  • platelets
  • platelet activation
  • endothelium
  • endothelin
  • antiplatelet treatment
  • coronary stenting
  • coronary angioplasty (PCI)
  • stable angina
  • angina treatment
  • angina—unstable
  • acute coronary syndrome
  • cardiac ultrasound
  • stents
  • echocardiography
  • EBM
  • angioplasty offsite
  • angiography
  • platelet and angioplasty
  • coronary syndromes
  • acute ischaemic syndromes
  • acute myocardial infarction
  • angina

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  • Funding This work was supported by unrestricted grants from Haemonetics and Medtronic UK.

  • Competing interests NC has received unrestricted research funding from Haemonetics, Medtronic, Boston Scientific and Pfizer. He has also received speaker/consulting fees from Boston Scientific, Abbott, Medtronic, AstraZeneca, Eli Lilly and Cordis. TW has received unrestricted research funding and speaker/consulting fees from AstraZeneca. JM has received honoraria and consulting fees from Medtronic and St. Jude. The remaining authors report no conflicts of interest.

  • Patient consent None.

  • Ethics approval The Southampton and South West Hampshire Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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