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The pivotal role of platelets in occlusive thrombus generation is well proven. This, in turn, forms the basis for maintenance antiplatelet therapy in Acute Coronary Syndrome (ACS) and posts Percutaneous Coronary Intervention (PCI) patients. Current guideline-based antiplatelet therapies promote a “one size fits all” concept despite multiple clinical studies consistently reporting heterogeneity of patient response to antiplatelet therapy. This led to the use of platelet function assays to objectively measure platelet inhibition. Although there is evidence showing a benefit of the use of platelet inhibition test directed antiplatelet therapy in post PCI patients, there is very little data on the use of platelet function assays in monitoring and tailoring treatment in individual patients on different antiplatelet regimens.
This was a prospective observational study done in a tertiary care cardiac center based in Kolkata between August 2014 and May 2015. We enrolled 124 patients for more than 3 months of Dual Antiplatelet Therapy (DAPT) post PCI. Dual antiplatelet therapy included Aspirin 150 mg once daily along with any of the following: Clopidogrel 75 mg once daily/ Clopidogrel 75 mg twice daily/ Prasugrel 10 mg daily/ Ticagrelor 90 mg twice daily. All 124 patients underwent Platelet Function Inhibition Assay using “Multiplate”. The Platelet Function Analyzer (Roche Diagnostics USA) 3-6 months after the initiation of DAPT. The cut off for the ADP-induced Platelet function inhibition assays were as in table 1. All patients were followed up for a mean period of 12 months. The Patients were stratified according to their antiplatelet regimens and quantum of platelet function inhibition. Depending on their level of platelet inhibition and bleeding tendencies DAPT regimens were modified accordingly on follow-up OPD visits. We also maintained a register to look for adverse bleeding events during the course of the study. Compliance to DAPT was ensured during the course of the study.
Of the 124 subjects included in this study 18 (14.5%) were females and the rest were males. All patients were posted Percutaneous coronary artery interventions on different dual antiplatelet regimens. Of the three standard dual antiplatelet (DAPT) regimens commonest regimen was aspirin with clopidogrel (49%) followed by prasugrel (34%) and ticagrelor (17%) in that order. Platelet inhibition was assessed in all groups were noted.
As noted in the below figures the newer antiplatelet agents like ticagrelor (mADP∼26U) and prasugrel (mADP∼26.11U) were almost equally potent and more efficacious in inhibiting platelet activity compared to clopidogrel (mADP∼38 to 48U).The homogeneity of results with newer antiplatelet agents like ticagrelor and prasugrel was also well established with none of the patients being in the “no inhibition group”. This study also shows the variable response to clopidogrel (even with twice daily dosing of clopidogrel) with almost 15% of patients in clopidogrel showing barely any platelet inhibition. All the 11 patients with a poor response to clopidogrel were either upgraded to prasugrel or ticagrelor. Despite being a non-responder to clopidogrel there was no increase in recurrent events of ACS/repeat revascularization. During the course of this study, we do not report any adverse fatal/non-fatal bleeding events.
Mandatory dual antiplatelet therapy remains the cornerstone of maintenance therapy in Post PCI patients. Despite the advent of newer more potent antiplatelet agents a significant population of Post PCI patients still continues on Clopidogrel and aspirin, predominantly due to economic constraints. Despite the heterogeneity of response to clopidogrel compared to the newer antiplatelets, no cases of repeat revascularization or adverse bleeds in any of the subgroups. Thus, platelet inhibition assays proved worthwhile not only in monitoring the response to antiplatelet therapy but also in titrating antiplatelet therapy and can be a useful adjunct in monitoring antiplatelet therapy in patients with high risk of bleeding/thrombosis. Based on our findings we have devised the following strategy regarding a choice of antiplatelet therapy in different subsets of patients with ACS undergoing PCI as illustrated in the figure below.