Individualised Antiplatelet Therapy - Is There a Role for Platelet Function Testing in Routine Clinical Practice?

Jean-Philippe Collet , Jochem Wouter van Werkum
Interventional Cardiology Review, 2010;5(1):96-103
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Abstract

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.
Keywords
Platelet reactivity, aspirin, clopidogrel, CYP2C19*2 polymorphism, prasugrel, ticagrelor, platelet function assay, point-of-care assay, flow cytometry, turbidometric light transmittance aggregometry (LTA)
Disclosure The authors have no conflicts of interest to declare.
Received: December 21, 2009 | Accepted March 08, 2010 | Citation Interventional Cardiology Review, 2010;5(1):96-103
Correspondence: Jean-Philippe Collet, Institut de Cardiologie – INSERM U 937, Groupe Hospitalier Pitié-Salpêtrière, 47–83, Bd de l’hopital, 75013, Paris, France. E: jean-philippe.collet@psl.aphp.fr; Jochem Wouter van Werkum, Department of Cardiology, St Antonius Hospital Nieuwegein, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands. E: woutervanwerkum@gmail.com

Antiplatelet therapy is the standard of care for patients with acute coronary syndromes (ACS) and/or patients undergoing percutaneous coronary intervention (PCI) with stenting.1–3 Plaque rupture and/or iatrogenic vascular damage during PCI would normally result in the development of intravascular thrombus. Findings across multiple investigations consistently demonstrate the effectiveness of dual antiplatelet therapy with aspirin and clopidogrel in the reduction of atherothrombotic complications, in both the short and long term.4 However, several recent studies have demonstrated wide inter-individual differences in the magnitude of on-treatment platelet reactivity.5–18 The heterogeneous nature of the response to oral antiplatelet therapy results in the so-called ‘high on-treatment platelet reactivity’ state in a substantial subset of patients; even more importantly, this state has been linked to adverse outcomes. Consequently, much attention is now being focused on monitoring antiplatelet inhibition as an evaluation of an individual patient’s pharmacological response to antiplatelet therapy.19

Limitations of Antiplatelet Therapies

Antiplatelet agents are downregulators of haemostasis. Although long-term use of oral antiplatelet therapies in patients with atherothrombotic burden can in fact reduce the incidence of atherothrombotic events, it has also been previously associated with a risk of bleeding.20,21 A further limitation associated with antiplatelet therapies is occasional poor pharmacological response or persistent high on-treatment platelet reactivity.

Aspirin

The routine administration of aspirin during cardiovascular interventions is associated with decreased atherothrombotic events. Aspirin preferentially and irreversibly inhibits the constitutively expressed cyclo-oxygenase-1 (COX-1) enzyme, which has regulatory housekeeping cellular functions including vascular haemostasis, gastric mucosal integrity and renal blood flow.

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