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

Abstract

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.

Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment

“…In addition, very recently, Timur et al [27] found a different percentage of aspirin resistance patients using AA-induced platelet aggregation and AA-induced TxB2 formation (5% and 28%, respectively); such percentage are very similar to those obtained in our study, even if they evaluated AA-induced TxB2 formation, while we evaluated serum TxB2 levels.…”

Association of thrombelastographic parameters with post-stenting ischemic events

“…Different tests have provided wide-ranging figures for the prevalence of clopidogrel resistance, suggesting poor correlation between currently available platelet function tests 18. Some platelet function test parameters are related to recurrent ischemic events although usage of aspirin which is regarded as aspirin resistance 19 20…”

Impact of pharmacogenetics on aspirin resistance: a systematic review

“…In our research, the most used laboratory method was the LTA, which is considered the gold standard for testing platelet function. 18 The relationship between polymorphisms and AR has been described by Yi et al This study assessed the interaction with PTGS1 (rs1236913 and rs3842787), PTGS2 (rs689466 and rs20417), TXAS1 (rs194149, rs2267679, and rs41708), P2RY1 (rs701265, rs1439010, and rs1371097), P2RY12 (rs16863323 and rs9859538), and ITGB3 (rs2317676 and rs11871251) gene variants. In the laboratory analysis, only rs1371097 of the P2RY1 gene, comparison CC x TT þ CT, obtained statistical relevance (p ¼ 0.01), even after adjusting for other covariates (p ¼ 0.002; OR ¼ 2.35; 95%CI: 1.87-6.86).…”