Platelet Function Testing in Contemporary Clinical and Interventional Practice

Abstract

Dual antiplatelet therapy with a combination of aspirin and an inhibitor of the ADP P2Y12 receptor is the recommended treatment for patients with acute coronary syndrome or who are undergoing percutaneous coronary intervention (PCI). However, patients may continue to have ischemic recurrences, including stent thrombosis, which have been linked with the well-known variability in individual response to antiplatelet therapy, and clopidogrel in particular. There are currently several assays available to measure platelet reactivity, and platelet function testing has been shown to be a valuable tool to assess the pharmacodynamic efficacy of antiplatelet drugs. Moreover, platelet reactivity has important prognostic implications, as several studies have shown an association with thrombotic and bleeding events in patients with high and low platelet reactivity, respectively. Consequently, over the past years there has been a plethora of studies investigating the optimal range of platelet reactivity associated with the highest protection against ischemic complications and the lowest risk of bleeding. Given the correlation between on-treatment platelet reactivity and outcomes, the use of platelet function testing has also been advocated to create personalized antiplatelet therapy. Several studies have been conducted in this field, but major clinical trials have failed to demonstrate a benefit of such a strategy in improving clinical outcomes. Indeed, inherent limitations of these trials may have contributed to their failure. The present manuscript provides an overview on the role of platelet function testing in contemporary clinical and interventional practice.

Switching P2Y12-receptor inhibitors in patients with coronary artery disease

“…46,69,70 Although a detailed description of these trials is beyond the scope of this manuscript, several drawbacks that are likely to have made a large contribution to the reported findings should be highlighted, most importantly the low clinical risk profile of the patient populations enrolled in these trials. 71 Ongoing randomized studies to assess the use of novel P2Y 12 -receptor therapies on the basis of results of pharma codynamic testing, such as the TROPICAL-ACS trial, 72 and genetic testing, such as the POPular Genetics trial, 73 in patients with ACS undergoing PCI, will provide more insights into this topic.…”

Role of genetic testing in patients undergoing percutaneous coronary intervention

“…The use of genetic testing as a tool to incorporate into routine clinical practice is also challenged by the fact that a parallel line of research focused on personalizing antiplatelet therapy based on results of platelet function testing has provided thus far disappointing results [121–124]. In fact, although observational studies in high-risk PCI settings have shown that modification of antiplatelet therapy based on results of platelet function studies are associated with favorable outcomes, these findings have not been corroborated within a number of randomized clinical trials [125]. It may be argued that these trials were flawed by target population, antiplatelet medications, platelet function assay, HPR cut-off values, timing of testing, among other variables, which were not adequate to test for the study hypothesis [125].…”

Defining the Link Between Chronic Kidney Disease, High Platelet Reactivity, and Clinical Outcomes in Clopidogrel-Treated Patients Undergoing Percutaneous Coronary Intervention

“…Although randomized clinical trials evaluating the use of platelet function testing to tailor antiplatelet therapy have failed to demonstrate any benefit, the main limitation of all these studies was the inclusion of low-risk populations. 20 The results of the study by Baber et al 15 clearly identify a subset of patients where further risk-markers may potentially help stratify patients to optimize antithrombotic therapy. Indeed, additional prospective studies are needed to better evaluate this hypothesis.…”