title: Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting.
abstract: Clopidogrel low-responsiveness assessed with multiple electrode platelet aggregometry (MEA) has been shown to be a strong and independent predictor of early stent thrombosis (ST) after coronary stenting. The relation of clopidogrel response status, as assessed with MEA, with incidence and timing of ST during an extended follow-up period has never been reported. Here, we report the six-month follow-up results of a prospective trial assessing clopidogrel responsiveness with MEA in patients undergoing percutaneous coronary intervention (PCI). A total of 1,608 consecutive patients with planned drug-eluting stent placement were enrolled in this study. Before PCI patients uniformly received 600 mg clopidogrel and blood was taken directly before PCI to measure ADP-induced platelet aggregation with MEA. The upper quintile (20%) of patients according to MEA measurements (n=323) was defined as clopidogrel low responders. Compared with normal responders (n=1,285), the cumulative incidence of definite ST within six months was significantly higher in low responders [2.5% vs. 0.4%; OR 6.5; 95% CI, 2.4-17.0; P<0.001]. The combined incidence of definite or probable ST was higher as well in low vs. normal responders [4.1% vs. 0.7%; OR 5.8; 95% CI, 2.8-12.3; P<0.0001]. A significant inverse correlation of MEA values and the timing of definite or probable ST (in days) was observed (Spearman coefficient = -0.45; P=0.04) with events occurring earlier in the low-responder group. MEA measurements are highly predictive for the occurrence of ST during the first six months following coronary stenting. In the majority of clopidogrel low responders suffering ST, the ischaemic event occurs early in the course after the procedure.
authors.affiliation: Deutsches Herzzentrum and 1. Medizinische Klinik rechts der Isar, Lazarettstrasse 36, 80636 München, Germany. dirk@sibbing.net
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
authors.forename: Tanja
authors.initials: T
authors.lastname: Morath
authors.forename: Siegmund
authors.initials: S
authors.lastname: Braun
authors.forename: Julia
authors.initials: J
authors.lastname: Stegherr
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogt
authors.forename: Albert
authors.initials: A
authors.lastname: Schömig
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.forename: Nicolas
authors.initials: N
authors.lastname: von Beckerath
mesh_terms: D000244:Adenosine Diphosphate; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D001780:Blood Coagulation Tests; D000077144:Clopidogrel; D016903:Drug Monitoring / Q000379:methods*; D004351:Drug Resistance; D054855:Drug-Eluting Stents; D005260:Female; D005858:Germany; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine