title: 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.
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance Publique Hôpitaux de Marseille, Aix-Marseille Université, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Uhry
authors.forename: Jacques
authors.initials: J
authors.lastname: Bessereau
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000601:surgery*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D004351:Drug Resistance / Q000235:genetics; D019317:Evidence-Based Medicine; D005838:Genotype; D006801:Humans; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011183:Postoperative Complications / Q000517:prevention & control*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D058925:Receptors, Purinergic P2Y12 / Q000032:analysis; D013876:Thiophenes / Q000627:therapeutic use; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin