title: How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors--is an algorithm the answer?
abstract: Within the past decade, high on-treatment platelet reactivity (HTPR) on clopidogrel and its clinical implications have been frequently discussed. Although it has been previously assumed that HTPR is a phenomenon occurring only in patients treated with clopidogrel, recent data show that HTPR might also occur during treatment with prasugrel or ticagrelor in the acute phase of ST-elevation myocardial infarction. Moreover, it has been postulated that there is a therapeutic window for P2Y12 receptor blockers, thus indicating that HTPR is associated with thrombotic events whereas low on-treatment platelet reactivity (LTPR) is associated with bleeding events. The current paper focuses on tools to identify risk factors for HTPR (pharmacogenomic testing, clinical scoring and drug-drug interactions) and on the use of platelet function testing in order to identify patients who might not respond adequately to clopidogrel. The majority of recent clinical randomised trials have not supported the hypothesis that platelet function testing and tailored antiplatelet therapy are providing a favourable clinical outcome. These trials, mainly performed in low-to-moderate risk patients, will be reviewed and discussed. Finally, an algorithm based on current knowledge is suggested, which might be of use for design of clinical trials.
authors.affiliation: Jolanta Siller-Matula, MD PhD, Department of Cardiology, Medical University of Vienna, Austria, E-mail: jolanta.siller-matula@meduniwien.ac.at.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrör
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Steen D
authors.initials: SD
authors.lastname: Kristensen
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
mesh_terms: D000465:Algorithms; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control*; D003661:Decision Support Techniques; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010979:Platelet Function Tests; D057285:Precision Medicine; D011237:Predictive Value of Tests; 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; D012307:Risk Factors; 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
keywords: Platelet reactivity; clopidogrel; prasugrel; ticagrelor