Does one size really fit all? The case for personalized antiplatelet therapy in interventional cardiology.

Cardiovascular disease is the leading cause of death worldwide. Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor, is currently recommended as a default for patients after acute coronary syndrome (ACS) and following percutaneous coronary intervention (PCI). However, controversies arise over the role of aspirin, the optimal duration of DAPT after drug-eluting stent (DES) implantation, the choice of P2Y12 inhibitor and the variability in individual responses to antiplatelet agents. Recent data indicate that monotherapy with a P2Y12 inhibitor may have adequate anti-ischemic effects with lower bleeding risk. Additionally, discrepancies in DAPT duration recommendations and the optimal P2Y12 inhibitor, provides more uncertainty. We ask the question "does one size really fits all?" or should a more personalized strategy should be implemented. Plain Language Summary Diseases affecting the heart and blood circulation are the leading cause of death worldwide. Treatment with drugs that prevents platelets from clumping (called antiplatelets) like aspirin plus another drug group (called P2Y12 inhibitors) like clopidogrel, ticagrelor and prasugrel, is currently recommended as a default for patients after heart attack and/or in whom coronary stents are inserted. However, it is very well documented that the response of any individual to these drugs is highly variable, and that the patients who don't respond as well to them are at increased risk of having clot events in their coronary arteries. On the other hand, people who respond to the drugs very sensitively have a higher bleeding risk. Despite these observations, there is no attempt to test the response of individuals patients to their antiplatelet drugs in routine practice. This review article looks in detail and whether the currently used strategy of "One size fits all" should be changed, given that there may well now be the chance to perform routine testing on everyone, and personalize their treatment accordingly. Article highlights Introduction The optimal antiplatelet strategy in acute coronary syndrome (ACS) patients, especially after drug-eluting stent implantation, is increasingly contentious. The current default antiplatelet regimen, which involves aspirin during the initial period of Dual antiplatelet therapy (DAPT) followed by its use as monotherapy, is being increasingly challenged. Controversies surrounding the optimal duration of DAPT and the optimal choice of P2Y12 inhibitor in a DAPT strategy generate uncertainty, particularly with inter-individual variable response to antiplatelets. In this review, we explore all these dilemmas in detail and specifically ask the question: "does one size fits all?". Variable response to antiplatelets The challenge: There is substantial variability in individual response to antiplatelet agents, specifically a proportion of the population will respond poorly (High on treatment platelet reactivity). By contrast, a proportion of individuals will be particularly sensitive to the drug (Low on treatment platelet reactivity). This introduces the concept of a therapeutic "sweet spot". There are currently two strategies to help personalize antiplatelet therapy which have not been fully adopted in current routine clinical practice. Variability in response to aspirin and flaws in arachidonic acid-based platelet function tests: Multiple studies have reported high prevalence of aspirin resistance, using arachidonic acid as the agonist to initiate platelet reactivity. We discuss the flaws behind using this method. Clopidogrel resistance, variable response and CYP2C19: There has been demonstrable variability in response to clopidogrel influenced by factors including gender and genotype, specifically carriers of CYP2C19 *2 and *3 alleles. Tests of phenotype and the link with ischemic events: There have been many attempts to assess the antiplatelet efficacy of clopidogrel and establish a relation with ischemic events. Tests of genotype and risk of ischemic events in patients on clopidogrel: Individuals carrying CYP2C19 loss of function alleles, have reduced levels of the active metabolite of clopidogrel. Was that linked to an increased risk of cardiovascular events? Clopidogrel withdrawal and clinical events in percutaneous coronary intervention (PCI) patients: The cessation of clopidogrel has been shown to be associated with ischemic clinical events, is there a "rebound phenomenon". Trials testing tailored therapy after PCI in patients with high on-treatment platelet reactivity (HTPR) on clopidogrel: Trials were designed to identify patients with HTPR and intervene in some way in order to modify the risk of ischemic events, However, there are some important concerns about the accuracy of the used assay (VerifyNow) in these studies. Stronger P2Y12 agents: more bleeding and still some hyporesponsiveness: Based upon the increasing concerns about the variability of response to clopidogrel, there was a strong stimulus for the development of P2Y12 inhibitors that were more potent. Is prasugrel or ticagrelor a better alternative to clopidogrel? Is there recorded hyporesponsiveness to these new agents? Shorter duration DAPT and antiplatelet monotherapy. Describing the real-world trials of reducing DAPT duration and using P2Y12 inhibitors as monotherapy as a potential replacement to aspirin. Should we personalize antiplatelet therapy in interventional cardiology by testing individual response and tailoring treatment accordingly? The case for TEG6S. Explaining the Thromboelastography (TEG) method, its ease of use as a bedside platelet function test (PFT) and its validation. Conclusion The case for routine testing of antiplatelet therapy is strong but could only be translated into clinical practice if a simple, quick, easy to use, accurate assay was available. [ABSTRACT FROM AUTHOR]