Introduction Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert Commentary The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes.

Diabetes mellitus (DM) is a metabolic disorder associated with accelerated atherogenesis and an increased risk of atherothrombotic complications. Multiple mechanisms contribute to the prothrombotic status which characterizes DM patients underscoring the importance of antiplatelet therapies used for secondary prevention in these patients. For many years, dual antiplatelet therapy (DAPT) with aspirin and the P2Y 12 inhibitor clopidogrel has represented the mainstay of treatment following an acute coronary syndrome (ACS) or in patients undergoing percutaneous coronary interventions (PCI). Although DAPT reduces the incidence of atherothrombotic recurrences, these rates remain high in DM patients underscoring the need for more efficacious therapies. Oral platelet P2Y 12 receptor inhibitors with enhanced potency, such as prasugrel and ticagrelor, as well as antiplatelet therapies such as vorapaxar inhibiting the thrombin-mediated platelet signaling pathway, constitute treatment opportunities for patients with DM and have shown to be associated with a greater reduction in ischemic recurrences, albeit at the cost of more bleeding. This article reviews currently available antiplatelet agents and delivers an update on the advances and drawbacks of these agents used for secondary prevention in DM patients experiencing an ACS or undergoing PCI.

URL: https://www.clinicaltrials.gov. Unique identifier: NCT02287909.