title: Clopidogrel cessation triggers aspirin rebound in patients with coronary stent.
abstract: OBJECTIVE
  Premature discontinuation of clopidogrel in patients undergoing percutaneous coronary intervention is a significant risk factor for thrombotic adverse outcomes. However, recent studies indicate that even discontinuation of long-term use of clopidogrel may be associated with multiple adverse outcomes, that is, rebound phenomenon whose mechanism is not definitely clear. The aim of the study was to examine the effect of clopidogrel withdrawal in those on combined aspirin and clopidogrel therapy.
  
  
  METHODS
  This prospective, multicenter study enrolled 200 patients who underwent coronary stent implantation and were on dual antiplatelet therapy (100 mg aspirin + 75 mg clopidogrel) 1 year after the stent placement. In all patients, we measured the platelet aggregation, by multiplate electrode aggregometry, using two agonists [adenosine diphosphate with PGE1 (ADPHS) and arachidonic acid (ASPI)] two times: on the day of cessation of clopidogrel and 90 days after clopidogrel was stopped.
  
  
  CONCLUSIONS
  Following clopidogrel discontinuation, we registered an increase in ASPI values (P < 0·001), linear correlation between changes in ASPI and ADPHS values (P = 0·009) and significant difference in the values of ASPI first quartile of ADPHS compared with the other three (P < 0·001, P = 0·016, P < 0·001, I vs. II, I vs. III and I vs. IV quartile of ADPHS, respectively).
  
  
  CONCLUSIONS
  Our findings show that cessation of clopidogrel causes loss of antiplatelet synergism with aspirin, leading to a weakening of the response to aspirin, which may be one explanation for the rebound after the clopidogrel cessation.
authors.affiliation: High Medical School Milutin Milankovic, Belgrade, Serbia.
authors.forename: N
authors.initials: N
authors.lastname: Djukanovic
authors.forename: Z
authors.initials: Z
authors.lastname: Todorovic
authors.forename: S
authors.initials: S
authors.lastname: Obradovic
authors.forename: S
authors.initials: S
authors.lastname: Njegomirovic
authors.forename: D
authors.initials: D
authors.lastname: Zamaklar-Trifunovic
authors.forename: D
authors.initials: D
authors.lastname: Protić
authors.forename: M
authors.initials: M
authors.lastname: Ostojic
mesh_terms: D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use*; D000077144:Clopidogrel; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D015607:Stents; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: aspirin rebound; clopidogrel cessation