Tailoring Antiplatelet Treatment | Feature

The unpredictable response to clopidogrel reported nearly a decade ago introduced us to the field of personalized antiplatelet therapy based on genetic and platelet function testing. Clinicians must now consider presentation, bleeding risk, and cost.

Important advances have occurred in our understanding of the platelets’ role in arterial thrombosis. These advances have enabled the development of new antiplatelet therapies. Clinical trials have demonstrated the benefit of antiplatelet therapy in a diverse range of cardiovascular diseases (CVD), including acute myocardial infarction, unstable angina, and ischemic stroke. The market for antiplatelet therapies has grown in recent years for several reasons, including the:

Aging population.
Global increase in CVD incidence due to diabetes.
Increased understanding of the role of antiplatelet therapy in the prevention and treatment of CVDs.

Prasugrel and ticagrelor are two antiplatelet agents that have been recently approved by the FDA for use in conjunction with aspirin to treat patients with acute coronary artery syndromes. In phase III trials, these agents have been shown to significantly reduce adverse cardiovascular events when compared with clopidogrel therapy. These additions to the antiplatelet therapy class can make it more challenging for clinicians to decide on what is most appropriate and beneficial for their patients. There is no longer just one option for antiplatelet therapy. Clinicians must now consider the optimal antiplatelet therapy for each patient depending on their presentation, bleeding risk, and cost.

Personalizing Approaches in Antiplatelet Treatment

The unpredictable response to clopidogrel reported nearly a decade ago introduced us to the field of personalized antiplatelet therapy based on genetic and platelet function testing. The CYP2C19 loss-of-function allele is a major independent predictor of the pharmacodynamic and clinical response to clopidogrel in PCI patients. Guidelines and FDA recommendations suggest that patients who are poor metabolizers, according to CYP2C19 testing, should be switched to an alternate antiplatelet therapy.

Genetic testing may facilitate the initial choice of antiplatelet therapy and give physicians the information they need to guide decisions in therapy prior to coronary interventions. The drawback, however, is that poor metabolizers are rare, and genetic testing doesn’t consider other drug–drug interactions and other influences that may affect patients’ responsiveness to clopidogrel. More evidence from prospective trials is required before genotyping can be implemented in standard practice.

The Role of High Platelet Reactivity

High platelet reactivity (HPR) is a new cardiac risk factor for recurrent adverse cardiovascular events after PCI that is increasingly being accepted by the medical community. Several platelet function assays are available to determine HPR. Unlike genetic testing, platelet function assays account for drug–drug interactions and other influences on platelet function, potentially leading to a more accurate assessment of antiplatelet effects. A disadvantage of platelet function testing, however, is that it must be performed after the antiplatelet agent has been administered and the patient has reached a steady state effect.

Looking Ahead in Antiplatelet Therapy

Future advances in antiplatelet therapy are likely to come from improvements in our understanding of the events that regulate thrombosis. We also need to determine factors that specifically promote hyper-reactive platelet responses at the sites of atherosclerotic plaque rupture. Currently, a large number of new antithrombotic therapies are under development, and personalized antiplatelet trials based on either genetic or platelet function testing are ongoing. The hope is these emerging therapies and studies on testing will further enhance our ability to optimize outcomes for our patients.

Additional Resources:

Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908-2913.

Bonello L, Tantry US, Marcucci R, et al; Working Group on High On-Treatment Platelet Reactivity. Consensus and future  directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919-933.

Gurbel PA, Tantry US, Shuldiner AR, Kereiakes DJ. Genotyping: one piece of the puzzle to personalize antiplatelet therapy. J Am Coll Cardiol. 2010;56:112-116.

Gurbel PA, Tantry US. Do platelet function testing and genotyping improve outcome in patients treated with antithrombotic agents? Circulation. 2012;125:1276-1287.

 

 

 

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