Comparison of four methods to assess high-on platelet reactivity under P2Y12 receptor inhibitor

Abstract

P2Y12 receptor inhibitors are antiplatelet agents commonly prescribed in the treatment of coronary artery disease. Their efficacy can be limited by high on-treatment platelet reactivity (HPR), which can be evaluated by different biological assays. Most commonly, HPR is evaluated by flow cytometric vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay, which can be time consuming. To evaluate the potential interest of novel technologies, we compared four different assays. Ninety patients receiving P2Y12 inhibitors were included. Four technologies were evaluated: the current standard test measuring VASP-P by flow cytometry, the historical reference test based on light transmittance aggregation (LTA), and two relatively novel techniques: whole blood multiple electrode aggregometry (MEA) and platelet function analyzer (PFA), which are less time consuming. The three latter tests were compared with the VASP-P assay as a reference using receiver operating characteristics (ROC) analysis: LTA has an excellent comparability with the VASP test (ROC AUC > 0.9); the other two tests (multiplate and PFA) have only satisfactory comparability (ROC AUC around 0.7) and therefore may not replace the VASP "gold standard" test, if importance is attached to a quantitative assessment of the substitution parameter of VASP. Nevertheless, if a binary approach of the anti-aggregation result is sought, then one can conclude that the three tests are equivalent since Cohen's kappa coefficients are very close for the three tests (k = 0.548 for LTA; k = 0.554 for MEA; k = 0.570 for PFA/P2Y), and a similar proportion of patients are misclassified (15% for LTA, 14% for MEA, and 13.6% for PFA). Discriminant factor analysis using all the parameters provided by each test did not improve the diagnostic performance of MEA or PFA. In conclusion, only LTA shows a good comparability to the VASP assay using ROC curve analysis, probably because misclassified patients have results close to the cutoff values. All three tests have moderate agreement regarding the classification of patients as responders to P2Y12 inhibition.

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve

“…The results are reported as a percentage of maximum platelet aggregation. High platelet reactivity was defined as maximum platelet aggregation > 59% (LTA 20 μM/L) [ 25 ].…”

Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: a randomised controlled proof-of-concept trial

“…The Multiplate test has been shown to best reflect the in vivo plasma concentrations of ticagrelor and its active metabolite compared to other tests (VerifyNow and VASP) [21]. Other studies have shown Multiplate, VASP and platelet function analyser tests to have moderate agreement regarding the classification of patients as responders to P 2 Y 12 inhibition [22]. Therefore, the Multiplate test is a valid method of evaluating platelet response to antiplatelet therapy in our patient cohort.…”

Net platelet clot strength of thromboelastography platelet mapping assay for the identification of high on-treatment platelet reactivity in post-PCI patients

“…Comparisons of various currently used PFTs have been extensively studied. Variations and poor concordances of different PFTs were demonstrated [ 17 , 35 ]. Before adopting a new PFT to be applied in clinics, correlation analysis between the new one and the gold standard method is generally performed.…”

“…LTA was developed in early 1960s, and has still been considered as a classical gold method to evaluate platelet reactivity [14]. However, LTA is characterized with lacking standardization, time-consuming, plasma based test, complicated sample preparation and professional expertise requirement, which limits its clinical routine application [15][16][17]. While the point-of-care test, TEGpm, meets the optimal PFT demands for clinical practice due to easy to perform, being available at bedside with flexible time and whole blood sample for testing.…”