Selection of P2Y12 antagonist, treatment initiation, and predictors of high on-treatment platelet reactivity in a "Real World" registry

Abstract

Objective: The present study aimed to compare characteristics related to selection of a P2Y₁₂ antagonist, investigate initiation of therapy with new-generation drugs, and identify predictors of high on-treatment platelet reactivity (HTPR) in patients with acute coronary syndrome treated with stent percutaneous coronary intervention (PCI).

Methods and results: Data from 589 patients in the LAPCOR (Laboratory AntiPlatelet efficacy and Clinical Outcome Registry; ClinicalTrials.gov Identifier: NCT02264912) registry was analyzed. P2Y₁₂ receptor antagonist efficacy was measured by VASP phosphorylation 24 ± 4 hours after a loading dose of clopidogrel (600 mg, N=407), prasugrel (60 mg, N=106), or ticagrelor (180 mg, N=76) and expressed by platelet reactivity index (PRI). HTPR was defined as PRI ≥50%. Patients treated with prasugrel were significantly younger and had significantly higher hemoglobin levels than those who received clopidogrel or ticagrelor, while chronic kidney disease was significantly more prevalent in the ticagrelor group. Almost all invasively managed patients given new-generation drugs received a loading dose after coronary angiography. Mean residual PRI and HTPR were significantly higher after clopidogrel (44.2 ± 23.1% and 42.2%, respectively) vs. prasugrel (17.7 ± 18.0% and 9.4%, respectively) or ticagrelor (18.8 ± 17.0% and 7.9%, respectively; all p<0.001). Among multiple variables tested, HTPR in patients treated with the new agents significantly related only to platelet count (p=0.014) and mean platelet volume (p=0.03).

Conclusion: Safety is the most important aspect under consideration in choosing new agents for an individual patient. Other than platelet count and mean platelet volume, factors known as predictors of higher platelet reactivity, did not influence the efficacy of new-generation P2Y₁₂ receptor antagonists.

Keywords: High residual platelet reactivity; P2Y(12) receptor antagonist; Platelet count; Platelet volume; Predictors; Selection.