title: Review of clopidogrel dose escalation in the current era of potent P2Y12 inhibitors.
abstract: Dual anti-platelet therapy with aspirin and a P2Y12 inhibitor is the standard of care for patients with acute coronary syndromes (ACS) and for patients undergoing percutaneous coronary intervention (PCI). Clopidogrel is associated with increased risk of high on-treatment platelet reactivity (HTPR) compared to ticagrelor and prasugrel. Investigators have therefore sought to "escalate" clopidogrel dosing to overcome HTPR to reduce ischemic/thrombotic events. In this review, we will summarize the evidence for dose escalation in the context of genetic determinants of resistance and platelet function data. We will review contemporary clinical trials that have sought to improve delivery of dual antiplatelet therapy to patients with coronary artery disease and discuss the potential of clopidogrel dose escalation in specific populations.
authors.affiliation: Division of Cardiology, University of North Carolina, Chapel Hill NC, North Carolina.
authors.forename: Lucius A
authors.initials: LA
authors.lastname: Howell
authors.forename: George A
authors.initials: GA
authors.lastname: Stouffer
authors.forename: Melissa
authors.initials: M
authors.lastname: Polasek
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Rossi
mesh_terms: D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: clopidogrel; genetic testing; individualized therapy; pharmacogenomics; platelet function testing