Platelet Function Analyzer-200 P2Y Results Are Predictive of the Risk of Major Adverse Cardiac Events in Korean Patients Receiving Clopidogrel Therapy Following Acute Coronary Syndrome

Abstract

BackgroundClopidogrel is one of the most commonly used anti-platelet agents in cardiovascular diseases. We analyzed the relationship between the platelet function analyzer (PFA)-200 P2Y (INNOVANCE PFA-200 System, Siemens Healthcare, Germany) results and occurrence of major adverse cardiac events (MACEs) in Korean patients with recent-onset acute coronary syndrome (ACS) taking clopidogrel.MethodsBetween August 2013 and June 2016, we prospectively enrolled 106 patients with recent-onset ACS who had been treated with clopidogrel. We obtained blood samples and measured closure time (CT) using the PFA-200 P2Y test. Patients were divided into two groups on the basis of a CT cut-off value of 106 seconds. We compared patient characteristics and various MACEs that occurred during the follow-up period.ResultsThe CTs for 78 patients exceeded the cut-off value. At the time of these analyses, 11 patients had been diagnosed with MACEs. In the time-to-event analysis, there was a difference between the two groups (P<0.001). After adjusting other variables associated with MACE occurrence, CT value was the strongest predictor of MACEs, with a 7.30-fold occurrence risk (P=0.002).ConclusionsWe found a strong relationship between CT and MACE risk in Korean patients with recent-onset ACS taking clopidogrel. Accordingly, PFA-200 P2Y results could be used as a predictive marker for MACE risk in such patients.

A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy

“…Our study determined platelet function using the INNOVANCE PFA-200 system (Siemens Healthcare, Germany) which assesses P2Y12-receptor blockades in patients undergoing therapy with P2Y12-receptor antagonists [ 47 ]. Despite some reports indicating a positive correlation between the CT value, HTPR, and MACE frequency [ 13 , 20 , 48 , 49 ], our findings failed to associate the molecular genotype and phenotype of HPR. This result can be attributed to several factors; (a) low frequency of LOF alleles (b) absence of patients with the homozygous genotype for LOF alleles (c) high frequency CYP2C19 *1/*1 with CT suggestive of HPR (d) potential overestimation of patients HPR (technical limitation of PFA-200); (e) involvement of new intronic and/or promoter variants and (f) heterogeneity of response to clopidogrel due to genes not evaluated in this study [ 5 , 50 ].…”

“…Similarly, it has been established that the use of platelet function tests such as PFA-200, Verify Now P2Y 12 assay and others are potentially predictive of the clinical response to clopidogrel [ 20 , 49 ]. Although not significant, intermediate metabolizers (at least one loss function allele) showed a trend towards decreasing CT values and therefore are more susceptible to HPR.…”

Changes in and significance of platelet function and parameters in Kawasaki disease

“…PFA-200 testing involves an easily automated process that takes a short time to get the test results 11 , which is a high-shear system using whole blood rather than platelet-rich plasma 12 . It simulates the characteristics of physiological platelet function 13 and measures the closure time (CT) required for platelets to plug an aperture simulating an injured vessel 14 , after platelet activation by relevant stimuli, namely collagen and epinephrine (EPI), or collagen and adenosine diphosphate (ADP) 15 .…”

The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing

“…We conducted analyses to determine the impact of genetic variables on clopidogrel responsiveness, utilizing the CT value, that has been described as a potential predictive biomarker [ 24 – 26 ]. Bivariate analyses indicated that five SNPs were significantly associated.…”