Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction

Eur J Pharmacol. 2014 Nov 5:742:47-54. doi: 10.1016/j.ejphar.2014.08.009. Epub 2014 Sep 6.


Substantial variability of antiplatelet action is an important limitation of clopidogrel. The aim of this study was to evaluate time-related changes in determinants of clopidogrel responsiveness in patients after myocardial infarction. The study population comprised 191 consecutive patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. ADP-induced platelet aggregation was tested with Multiplate Analyzer. Patients with ADP-PA>46.8U were defined as clopidogrel non-responders. The prevalence of clopidogrel non-responsiveness was highest during hospitalization and at 9 month follow-up visit, while it was lowest at 3 and 6 months after myocardial infarction (P=0.004). According to multivariate analysis, platelet count, mean platelet volume, concentration of hsCRP and leukocyte count influenced ADP-induced platelet aggregation in multiple assessment points. BMI, concentrations of hemoglobin, glycated hemoglobin, and BNP, hematocrit, adherence to medication, and patient׳s age were found to be independent predictors of high on-treatment ADP-induced platelet aggregation only at a single follow-up visit. Determinants of clopidogrel responsiveness in patients after myocardial infarction change within the long-term therapy. During hospitalization and early after discharge only biological factors affect ADP-induced platelet aggregation, while non-adherence to antiplatelet therapy may be a significant factor in determining clopidogrel non-responsiveness during late follow-up visits.

Keywords: ADP-induced platelet aggregation; Clopidogrel; Effectiveness of antiplatelet therapy; Myocardial infarction.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Aged
  • Clopidogrel
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Medication Adherence
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / therapy
  • Percutaneous Coronary Intervention
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors


  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine