Latest Evidence in Personalized Antiplatelet Therapy in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention

Abstract

In patients with acute coronary syndromes undergoing percutaneous coronary intervention, the combination of aspirin and clopidogrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist, is the gold standard of antiplatelet therapy. Two more potent P2Y12 ADP receptor antagonists are now available. Pharmacodynamic studies have revealed a large interindividual variability in the biological response to clopidogrel that is primarily related to variable active metabolite generation, depending on clinical factors, drug-drug interactions, and genetic polymorphisms. Several assays to measure platelet function are available and have revealed a high prevalence of high on-treatment platelet reactivity (HTPR). Patients exhibiting HTPR after a clopidogrel loading dose have a higher risk of thrombotic recurrence after percutaneous coronary intervention. A recent consensus has defined HTPR for the main platelet assays available (using receiver operating characteristic curve analysis) to define the optimal cutoff value for each assay in order to predict thrombotic recurrences. In this article, we present several lines of evidence that suggest a therapeutic window of platelet reactivity inhibition with P2Y12 ADP receptor antagonists. Such a paradigm shift is supported by the results of the Platelet Inhibition and Patient Outcomes (PLATO) trial and the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38, which showed the superiority of ticagrelor and prasugrel on thrombotic events compared with clopidogrel; however, these 2 medications had an increased bleeding rate. With the results of these trials, in addition to the evidence of a therapeutic window with P2Y12 ADP receptor antagonists, we summarize the potential of platelet reactivity monitoring and pharmacogenomics to tailor therapy.

Association of VEGFR-2 Gene Polymorphisms With Clopidogrel Resistance in Patients With Coronary Heart Disease

“…29 Therefore, we propose that VEGFR-2 genetic polymorphisms may cause structural changes in the receptor and lead to aberrant activation of multiple pathways, including its interaction with P2Y(2)R, with an overall influence on platelet aggregation, which is correlated with CR. [30][31][32] Patients carrying the TT genotype of VEGFR-2 +1192C.T (rs2305948) polymorphism exhibited significantly higher MACE, whereas the GG genotype of …”

Inhibidores del receptor plaquetario P2Y12. Parte 2 de 2: etiología, diagnóstico y manejo de la resistencia

“…Desde el año 2010 se ha introducido este concepto en la antiagregación plaquetaria, en donde los pacientes subagregados, incluidos aquellos que presentan resistencia a los antiagregantes independiente de la causa con la cual está asociada, están sujetos a un mayor riesgo de una complicación trombótica [21,23,83,84,150, y los sobreantiagregados están sujetos a un mayor riesgo de una complicación hemorrágica [19,172,181,184,187,189,[199][200][201][202]. Como resultado de lo anterior, el concepto de antiagregación personalizada con base en pruebas de laboratorio [11,12,16,18,21,23,25,26,[203][204][205][206] se ha abierto paso en los últimos años. Estos conceptos serán analizados en los siguientes subtítulos.…”