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

https://doi.org/10.1016/j.jacc.2008.11.030Get rights and content
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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

Cited by (0)

Material for platelet function analysis on the Multiplate device were provided free of charge from Dynabyte (Munich, Germany). Dr. Sibbing received speaker fees from Dynabyte. Dr. von Beckerath received speaker fees from Eli Lilly and fees for advisory board activities from Eli Lilly and Sanofi-Aventis. Dr. Kastrati received speaker fees from Eli Lilly, Sanofi-Aventis, and Bristol-Myers Squibb.