title: Predictors of antiplatelet response to prasugrel during maintenance treatment.
abstract: Insufficient P2Y12 receptor inhibition is associated with a higher risk of thrombotic events after percutaneous coronary intervention (PCI). The third generation thienopyridine prasugrel achieves stronger platelet inhibition as compared to its predecessor clopidogrel. Little is known about predictors of prasugrel drug responsiveness. The aim of this study was to explore predictors of prasugrel responsiveness in patients with a recent PCI on prasugrel maintenance dose (MD) treatment. In a registry of PCI-treated patients (n = 163, recruited between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced platelet aggregation (PA) was assessed on a Multiplate analyzer. The mean (interquartile range (IQR)) ADP-induced PA on prasugrel MD treatment was 206 (138-331) AU × min. Obese (defined by a body mass index (BMI) ≥ 30) patients (n = 42) (303 [192-467] vs. 187 [117-305] AU × min, p = 0.0001), patients (n = 70) with a history of clopidogrel low responsiveness (278 [161-409] vs. 192 [126-282] AU × min, p = 0.002) and patients (n = 18) on a low (5 mg) prasugrel MD (483 [252-798] vs. 198 [133-313] AU × min; p = 0.0001) showed higher PA values on prasugrel MD as compared to the remaining patients. In a multivariable linear regression model, the latter three variables were independently associated with higher PA values on prasugrel MD treatment. In summary response variability is observed in patients on prasugrel MD treatment. Obesity, a history of clopidogrel low responsiveness and a reduced prasugrel MD of 5 mg are independent predictors of an attenuated response to prasugrel treatment. Further studies are needed to explore clinical implications of this observation.
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München , Munich , Germany .
authors.forename: Katharina
authors.initials: K
authors.lastname: Mayer
authors.forename: Martin
authors.initials: M
authors.lastname: Orban
authors.forename: Isabell
authors.initials: I
authors.lastname: Bernlochner
authors.forename: Siegmund
authors.initials: S
authors.lastname: Braun
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulz
authors.forename: Lisa
authors.initials: L
authors.lastname: Gross
authors.forename: Martin
authors.initials: M
authors.lastname: Hadamitzky
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003328:Coronary Thrombosis / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D012042:Registries; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride
keywords: Clopidogrel; high on-treatment platelet reactivity; obesity; prasugrel; prasugrel responsiveness