Multi-parameter assessment of platelet inhibition and its stability during aspirin and clopidogrel therapy

摘要

Introduction Poor response to antiplatelet drugs is associated with adverse outcomes. We assessed platelet inhibition and its stability and tested correlation and agreement between platelet function assays. Methods Peripheral blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous coronary intervention (PCI) was collected at hospital discharge (visit-1) and at 30-90 days (visit-2). Platelet function was measured using light transmission aggregometry (LTA-AA and LTA-ADP), VerifyNow? (Aspirin; ARU and P2Y12; PRU), ex vivo TxB2, urinary 11dhTxB2, and VASP (PRI) assays. Data were analyzed as continuous, quartiles and binary. Patients were defined as aspirin poor responder (PR) with ARU ≤ 550, LTA-AA maximum ≤ 20%, TxB2 ≤ 1 ng/mL or 11dhTxB2 ≤ 1,500 pg/mg of creatinine and as clopidogrel PR with PRU ≤ 240, PRU ≤ 208, LTA-ADP maximum ≤ 40%, PRI ≤ 50%, or PRI ≤ 66%. Results Aspirin PR was 3-33% and clopidogrel PR was 10-35% in visit-1. LTA-AA, 11dhTxB2, and all clopidogrel-response measures showed correlation and agreement between visit-1 and visit-2. The highest agreement between two visits was revealed by PRU ≤ 240 and PRI ≤ 66% (PRU-κ = 0.7, 95% CI = 0.47, 0.93; PRI-κ = 0.69, 95% CI = 0.42, 0.95, p-values 0.001). Comparison of platelet function assays in a single visit (visit-1) revealed a poor correlation between LTA-AA and 11dhTxB2 assays and no agreement among aspirin-response assays. The highest correlation and agreement were obtained between VerifyNow? P2Y12 and VASP assays (rho = 0.7, p-value 0.001 and PRU ≤ 208-PRI-κ = 0.41-0.42, 95% CI = 0.13, 0.69, p-values 0.001). Conclusions Platelet inhibition is stable during aspirin and clopidogrel treatment. Clopidogrel-response assays correlate and agree with each other better than aspirin-response assays.