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J Am Coll Cardiol, 2009; 53:849-856, doi:10.1016/j.jacc.2008.11.030
© 2009 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Platelet Reactivity After Clopidogrel Treatment Assessed With Point-of-Care Analysis and Early Drug-Eluting Stent Thrombosis

Dirk Sibbing, MD*, Siegmund Braun, MD, Tanja Morath, MS, Julinda Mehilli, MD, Wolfgang Vogt, MD, Albert Schömig, MD, Adnan Kastrati, MD and Nicolas von Beckerath, MD

Deutsches Herzzentrum and 1. Medizinische Klinik rechts der Isar, Technische Universität München, Munich, Germany

Manuscript received July 21, 2008; revised manuscript received October 9, 2008, accepted November 2, 2008.

* Reprint requests and correspondence: Dr. Dirk Sibbing, Deutsches Herzzentrum and 1. Medizinische Klinik rechts der Isar, Lazarettstrasse 36, 80636 München, Germany (Email: dirk{at}sibbing.net).

Objectives: 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.

Key Words: clopidogrel • stent thrombosis • platelet aggregation • whole blood aggregometry

Abbreviations and Acronyms
  ADP = adenosine diphosphate
  AU = aggregation units
  CAD = coronary artery disease
  CI = confidence interval
  DES = drug-eluting stent(s)
  HR = hazard ratio
  LTA = light transmission aggregometry
  MEA = multiple electrode platelet aggregometry
  MI = myocardial infarction
  NSTEMI = non–ST-segment elevation myocardial infarction
  OR = odds ratio
  PCI = percutaneous coronary intervention
  ROC = receiver-operator characteristic
  ST = stent thrombosis
  STEMI = ST-segment elevation myocardial infarction
  TIMI = Thrombolysis In Myocardial Infarction
  VASP = vasodilator-stimulated phosphoprotein


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