The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI
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2018
Authors
Pavlović, MilanApostolović, Svetlana
Stokanović, Dragana
Lilić, Jelena
Konstantinović, Sandra S.
Zvezdanović, Jelena B.
Marinković, Valentina

Nikolić, Valentina N.
Article (Published version)

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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 / STEMISource:
International Journal of Clinical Pharmacy, 2018, 40, 6, 1482-1489Publisher:
- Springer, Dordrecht
Funding / projects:
DOI: 10.1007/s11096-018-0730-9
ISSN: 2210-7703
PubMed: 30367373
WoS: 000452049100009
Scopus: 2-s2.0-85055747811
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PharmacyTY - 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 . .