Title: Platelet Reactivity After Clopidogrel Treatment Assessed With Point-of-Care Analysis and Early Drug-Eluting Stent Thrombosis
Topic: Interventional Cardiology
Date Posted: 3/2/2009 5:00:00 PM
Author(s): Sibbing D, Braun S, Morath T, et al.
Citation: J Am Coll Cardiol 2009;53:849-856.
Clinical Trial: No

Study Question: What is the relationship between platelet reactivity to clopidogrel assessed with multiple electrode platelet aggregometry (MEA) and the risk of early drug-eluting stent thrombosis (ST)?

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

Results: The upper quintile of patients according to MEA measurements (n = 323) were 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], 3.1-28.4; p < 0.0001). Mortality rates were 1.2% in low versus 0.4% in normal responders (OR, 3.2; 95% CI, 0.9-11.1; 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, 2.2-11.6; p < 0.001).

Conclusions: The authors concluded that low response to clopidogrel assessed with MEA is significantly associated with an increased risk of ST.

Perspective: The current study reports that a low response to clopidogrel treatment assessed with MEA is significantly associated with an increased risk of ST. This study strengthens the hypothesis that ischemic events largely occur above a threshold of platelet reactivity to ADP, as measured by an ex vivo method. However, parenteral antiplatelet therapy was not evaluated as a potential confounder, and timing of platelet function measurements was highly variable in this analysis. Given these limitations, the cause and effect of high ontreatment platelet reactivity to ADP and ischemic events remain incompletely answered. The ongoing Gauging Responsiveness With A VerifyNow Assay-Impact On Thrombosis And Safety (GRAVITAS) trial and other prospective large-scale trials should help determine whether tailored antiplatelet treatment based on platelet function testing could improve the clinical outcome of patients after coronary stenting.  Debabrata Mukherjee, M.D., F.A.C.C.