International Journal of Clinical Pharmacy

, Volume 40, Issue 6, pp 1482–1489 | Cite as

The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI

  • Milan Pavlovic
  • Svetlana Apostolovic
  • Dragana Stokanovic
  • Jelena Lilic
  • Sandra S. Konstantinovic
  • Jelena B. Zvezdanovic
  • Valentina Marinkovic
  • Valentina N. NikolicEmail author
Research Article


Background A significant number of ischemic events occur even when adhering to dual antiplatelet therapy including aspirin and clopidogrel. Objectives The aim of our study was to determine predictors of long-term patient clinical outcome, among variables such as prodrug clopidogrel and intermediary metabolite 2-oxoclopidogrel concentrations, as well as patients’ clinical characteristics. Setting Department for the Treatment of Acute Coronary Syndrome in tertiary teaching hospital, Serbia. Methods This study enrolled 88 consecutive patients with first STEMI, treated with primary PCI, within 6 h of the chest pain onset and followed them 40 months. On the third day of hospitalization, blood samples were collected from each patient to measure clopidogrel and its metabolite 2-oxo-clopidogrel concentration by UHPLC-DAD-MS method. Main outcome measure Mortality from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for urgent myocardial revascularization or heart failure. Results The composite clinical outcome of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for urgent myocardial revascularization or heart failure, was registered in 31 patients (35.2%) during the 40-month follow-up. Lower clopidogrel (p < 0.05) and dose-adjusted clopidogrel concentrations (p < 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p < 0.001) and creatinine clearance (p < 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p < 0.05). Conclusion Clopidogrel dose-adjusted plasma concentration in STEMI patients, as well as multivessel coronary artery disease, showed significance in predicting an unfavorable composite clinical outcome after 40-month follow-up.


Clinical outcome Clopidogrel Coronary artery disease Fentalyl- co-medication STEMI 



This study was partially funded by Grant Nos. III 41018, 45001, and 34012 from the Serbian Ministry of Education, Science and Technological Development.

Conflicts of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Milan Pavlovic
    • 1
    • 2
  • Svetlana Apostolovic
    • 1
    • 2
  • Dragana Stokanovic
    • 3
  • Jelena Lilic
    • 4
  • Sandra S. Konstantinovic
    • 5
  • Jelena B. Zvezdanovic
    • 5
  • Valentina Marinkovic
    • 6
  • Valentina N. Nikolic
    • 3
    • 7
    Email author
  1. 1.Department of Internal Medicine—Cardiology, Medical FacultyUniversity of NisNisSerbia
  2. 2.Clinic for Cardiovascular DiseasesClinical Centre NisNisSerbia
  3. 3.Department of Pharmacology and Toxicology, Medical FacultyUniversity of NisNisSerbia
  4. 4.Medical FacultyUniversity of NisNisSerbia
  5. 5.Department of Chemistry, Faculty of TechnologyUniversity of NisLeskovacSerbia
  6. 6.Department of Social Pharmacy and Pharmaceutical Legislation, Faculty of PharmacyUniversity of BelegradeBelgradeSerbia
  7. 7.Medicinski fakultetNisSerbia

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