Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis.
OBJECTIVE
The aim of this prospective trial was to assess whether platelet reactivity to clopidogrel assessed with multiple electrode platelet aggregometry (MEA) correlates with the risk of early drug-eluting stent thrombosis (ST).


BACKGROUND
Studies using light transmission aggregometry (LTA) have shown that insufficient suppression of platelet reactivity to adenosine diphosphate (ADP) after clopidogrel treatment is associated with an increased risk of adverse cardiovascular events after percutaneous coronary intervention (PCI). However, LTA is time- and labor-intensive and inconvenient for the routine. A point-of-care assay with similar predictive power would be of great value.


METHODS
Between February 2007 and April 2008, a total of 1,608 consecutive patients with coronary artery disease and planned drug-eluting stent implantation were enrolled. Before PCI, all patients received 600 mg clopidogrel. Blood was obtained directly before PCI. The ADP-induced platelet aggregation was assessed in whole blood with MEA on a Multiplate analyzer (Dynabyte, Munich, Germany). The primary end point was definite ST at 30 days.


RESULTS
The upper quintile of patients according to MEA measurements (n = 323) was defined as clopidogrel low responders. Compared with normal responders (n = 1,285), low responders had a significantly higher risk of definite ST within 30 days (2.2% vs. 0.2%; odds ratio [OR]: 9.4; 95% confidence interval [CI]: 3.1 to 28.4; p < 0.0001). Mortality rates were 1.2% in low versus 0.4% in normal responders (OR: 3.2; 95% CI: 0.9 to 11.1; p = 0.07). The composite of death or ST was higher in low versus normal responders (3.1% vs. 0.6%; OR: 5.1; 95% CI: 2.2 to 11.6; p < 0.001).


CONCLUSIONS
Low response to clopidogrel assessed with MEA is significantly associated with an increased risk of ST. Further studies are warranted to evaluate the ability of MEA to guide antiplatelet therapy in patients undergoing PCI.
Sibbing
Dirk
D
Deutsches Herzzentrum and Medizinische Klinik rechts der Isar, Technische Universität München, Munich, Germany. dirk@sibbing.net
Braun
Siegmund
S
Morath
Tanja
T
Mehilli
Julinda
J
Vogt
Wolfgang
W
Schömig
Albert
A
Kastrati
Adnan
A
von Beckerath
Nicolas
N
D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000401:mortality / Q000628:therapy; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D017097:Electric Impedance; D004566:Electrodes; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods*; D019095:Point-of-Care Systems; D011446:Prospective Studies; D013927:Thrombosis / Q000453:epidemiology* / Q000209:etiology; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine