title: [Current options to manage clopidogrel poor responsiveness].
abstract: Antiplatelet therapy (aspirin + clopidogrel) is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions (PCI). More than 40 million patients worldwide receive clopidogrel, but about 20% of them are nonresponders or poor responders. Many studies using different techniques, platelet agonists and definitions have shown that patients who are poor responders to clopidogrel have an increased risk of death, reinfarction and stent thrombosis. The mechanisms leading to poor responsiveness are not fully elucidated and are likely multifactorial: genetic factors, accelerated platelet turnover, up-regulation of the P2Y12 pathways, high baseline platelet reactivity, poor compliance, underdosing and drug-drug interactions. The management of these patients is very difficult, but evidence does exist showing that a strategy of higher maintenance dose or switch to different thienopyridines (e.g. ticlopidine or prasugrel) or use of glycoprotein IIb/IIIa inhibitors during PCI may be helpful to overcome poor responsiveness and improve the long-term clinical outcome. This review describes the impact of poor responsiveness to clopidogrel on clinical outcomes, the mechanisms leading to poor effect, and the different assays to assess it. Finally, current and future options for its management are discussed.
authors.affiliation: U.O. di Cardiologia, Azienda Ospedaliera Universitaria S. Anna, Ferrara.
authors.forename: Luca
authors.initials: L
authors.lastname: Fileti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campo
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.forename: Jlenia
authors.initials: J
authors.lastname: Marchesini
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D004347:Drug Interactions; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000627:therapeutic use; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine