Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy

Abstract

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Resistance on the Latest Oral and Intravenous P2Y12 ADP Receptor Blockers in Patients with Acute Coronary Syndromes: Fact or Myth?

“…The assay uses platelet stimulation with specific inducers (ADP) to activate platelet aggregation. Once the aggregated platelets attach the sensor wires in the Multiplate ® device, electrical resistance (impedance) is detected and displayed as aggregation units (AUs) against time (area under the curve = AUC) [ 32 ]. VerifyNow ® (Werfen, Barcelona, Spain) assay is performed as a point-of-care test using a citrated whole blood sample.…”

“…Moreover, the examination itself (due to a simple technique) and the interpretation of results can be carried out easily (there is no need for skilled staff to perform and/or evaluate the results). Both assays have been used for PFT in post-marketing studies, including randomized ones [ 26 , 30 , 32 ]. Platelet function assay-100 = PFA-100 ® (Siemens Medical Solutions, Malvern, PA, USA) is another point-of-care assay, which can be used to monitor the effect of P2Y12 ADPRB.…”

“…The time taken for complete occlusion of the aperture is recorded as closure time (CT). Prolonged CT indicates a better response to ADPRB [ 32 ]. PFA-100 ® assay has been used in clinical studies mostly for the detection of aspirin resistance [ 33 , 34 ]; however, there are data to show that the test can be used also for the determination of response to ADPRB [ 35 ].…”

Резистентность К Антиагрегантным Препаратам: Механизмы, Роль Коморбидности И Других Клинических Факторов

“…Частота выявления резистентности к К варьирует в зависимости от используемых методов и составляет, по разным данным, от 4 до 30% [39][40][41].…”

Does individualized guided selection of antiplatelet therapy improve outcomes after percutaneous coronary intervention? A systematic review and meta-analysis

“…However, recent evidence suggests that a category of patients do not respond adequately to this medication, resulting in increased on-treatment platelet reactivity (HPR) and rates of atherothrombotic events [ [4] , [5] , [6] ]. A major factor of variable clopidogrel efficacy includes a loss-of-function genetic variation in the cytochrome P450 2C19 ( CYP2C19) gene, which plays a role in altering clopidogrel into its biologically active metabolite, which then irreversibly binds to the P2Y 12 receptor thus inhibiting ADP-induced platelet aggregation [ 7 , 8 ]. In recent years, alternative P2Y 12 receptor inhibitors, prasugrel and ticagrelor, have been developed and have been investigated to be superior to clopidogrel in terms of platelet inhibition and reduction of major adverse cardiovascular events, but are associated with a higher risk of bleeding complications [ 5 , [9] , [10] , [11] ].…”