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

Authorized Users Only
2018
Authors
Pavlović, Milan
Apostolović, Svetlana
Stokanović, Dragana
Lilić, Jelena
Konstantinović, Sandra S.
Zvezdanović, Jelena B.
Marinković, Valentina
Nikolić, Valentina N.
Article (Published version)
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Abstract
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 6h of the chest pain onsetand 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 lt 0.05) and dose-adjusted clopidogrel concentrations (p lt 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p lt 0.001) and creatinine clearance (p lt 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p lt 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.

Keywords:
Clinical outcome / Clopidogrel / Coronary artery disease / Fentalyl-co-medication / STEMI
Source:
International Journal of Clinical Pharmacy, 2018, 40, 6, 1482-1489
Publisher:
  • Springer, Dordrecht
Funding / projects:
  • Preventive, therapeutic, and ethical approach in preclinical and clinical studies of the genes and modulators of redox cell signaling in immune, inflammatory and proliferative cell response (RS-41018)

DOI: 10.1007/s11096-018-0730-9

ISSN: 2210-7703

PubMed: 30367373

WoS: 000452049100009

Scopus: 2-s2.0-85055747811
[ Google Scholar ]
1
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3094
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Pavlović, Milan
AU  - Apostolović, Svetlana
AU  - Stokanović, Dragana
AU  - Lilić, Jelena
AU  - Konstantinović, Sandra S.
AU  - Zvezdanović, Jelena B.
AU  - Marinković, Valentina
AU  - Nikolić, Valentina N.
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3094
AB  - 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 6h of the chest pain onsetand 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 lt 0.05) and dose-adjusted clopidogrel concentrations (p lt 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p lt 0.001) and creatinine clearance (p lt 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p lt 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.
PB  - Springer, Dordrecht
T2  - International Journal of Clinical Pharmacy
T1  - The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI
VL  - 40
IS  - 6
SP  - 1482
EP  - 1489
DO  - 10.1007/s11096-018-0730-9
ER  - 
@article{
author = "Pavlović, Milan and Apostolović, Svetlana and Stokanović, Dragana and Lilić, Jelena and Konstantinović, Sandra S. and Zvezdanović, Jelena B. and Marinković, Valentina and Nikolić, Valentina N.",
year = "2018",
abstract = "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 6h of the chest pain onsetand 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 lt 0.05) and dose-adjusted clopidogrel concentrations (p lt 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p lt 0.001) and creatinine clearance (p lt 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p lt 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.",
publisher = "Springer, Dordrecht",
journal = "International Journal of Clinical Pharmacy",
title = "The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI",
volume = "40",
number = "6",
pages = "1482-1489",
doi = "10.1007/s11096-018-0730-9"
}
Pavlović, M., Apostolović, S., Stokanović, D., Lilić, J., Konstantinović, S. S., Zvezdanović, J. B., Marinković, V.,& Nikolić, V. N.. (2018). The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI. in International Journal of Clinical Pharmacy
Springer, Dordrecht., 40(6), 1482-1489.
https://doi.org/10.1007/s11096-018-0730-9
Pavlović M, Apostolović S, Stokanović D, Lilić J, Konstantinović SS, Zvezdanović JB, Marinković V, Nikolić VN. The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI. in International Journal of Clinical Pharmacy. 2018;40(6):1482-1489.
doi:10.1007/s11096-018-0730-9 .
Pavlović, Milan, Apostolović, Svetlana, Stokanović, Dragana, Lilić, Jelena, Konstantinović, Sandra S., Zvezdanović, Jelena B., Marinković, Valentina, Nikolić, Valentina N., "The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI" in International Journal of Clinical Pharmacy, 40, no. 6 (2018):1482-1489,
https://doi.org/10.1007/s11096-018-0730-9 . .

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