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Sustained increase in platelet aggregation after the cessation of clopidogrel

Nina Djukanovic1, Zoran Todorovic2, Danijela Zamaklar-Trifunovic3

  • 1High Medical School Milutin Milankovic, Belgrade, Serbia.

Clinical and Experimental Pharmacology & Physiology
|October 31, 2015
PubMed

Insights

Stopping clopidogrel after one year of treatment did not lead to thrombotic events in patients with coronary stents. However, abrupt cessation can cause a sustained increase in platelet aggregation to other stimuli.

Area of Science:

  • Cardiology
  • Pharmacology
  • Hematology

Background:

  • Clopidogrel is a P2Y12 inhibitor commonly used after coronary stent implantation.
  • The long-term effects of clopidogrel cessation on platelet function are not fully understood.
  • Platelet hyperaggregability post-cessation may influence thrombotic risk.

Purpose of the Study:

  • To investigate the impact of abrupt, one-year clopidogrel cessation on thrombotic events.
  • To explore the causes of sustained increases in platelet aggregability after clopidogrel withdrawal.
  • To assess the relationship between rebound platelet aggregation and response to other agonists.

Main Methods:

  • Prospective, multicentre study of 200 patients with coronary stents on aspirin + clopidogrel.
  • Platelet aggregation measured using ADP + PGE1 (ADPHS), thrombin receptor activating peptide (TRAP), and arachidonic acid (ASPI).
  • Analysis of platelet aggregation at 10, 45, and 90 days post-clopidogrel cessation, stratified by ADPHS response.

Main Results:

  • Abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events.
  • Platelet aggregation stimulated by ADP + PGE1 significantly increased 10-90 days after clopidogrel cessation.
  • Patients with early pronounced rebound phenomena showed long-term increased platelet aggregation to TRAP and ASPI.

Conclusions:

  • One-year clopidogrel cessation appears safe regarding thrombotic events in this cohort.
  • Early rebound hyperaggregability to ADP predicts sustained increased platelet reactivity to other agonists.
  • Complex interactions between various agonists influence platelet function following clopidogrel withdrawal.

Keywords:
clopidogrelplatelet aggregationplatelet agonistsrebound

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