title: High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials.
abstract: Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) has substantially decreased the rate of cardiovascular events. Within the past decade, the variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. The variability in response could be linked to genetic polymorphisms impacting on activity of cytochrome P450 enzymes as well as clinical and demographic variables, but, taken together, factors identified so far can explain only up to approximately 12% of this variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. Regulatory agencies as well as major cardiac societies suggest the use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients with reduced effectiveness of clopidogrel. This review will focus on the current status of alternate strategies for more sufficient suppression of high platelet reactivity.
authors.affiliation: Universitaets-Herzzentrum Freiburg-Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Suedring 15, Bad Krozingen, Germany. dietmar.trenk@universitaets-herzzentrum.de
authors.forename: D
authors.initials: D
authors.lastname: Trenk
authors.forename: S D
authors.initials: SD
authors.lastname: Kristensen
authors.forename: W
authors.initials: W
authors.lastname: Hochholzer
authors.forename: F-J
authors.initials: FJ
authors.lastname: Neumann
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D004347:Drug Interactions; D019317:Evidence-Based Medicine; D006801:Humans; D010597:Pharmacogenetics; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D018570:Risk Assessment; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine