Background-The clinical impact of platelet aggregation assessed by point-of-care assays is unknown. We sought to evaluate whether high residual platelet reactivity (RPR) to ADP during clopidogrel therapy, measured by a point-of-care assay, predicts adverse clinical events in acute coronary syndrome patients undergoing percutaneous coronary intervention. Methods and Results-We used the VerifyNow P2Y12 assay (Accumetrics Inc, San Diego, Calif) to determine RPR to ADP in 683 patients with acute coronary syndrome undergoing dual-antiplatelet therapy who underwent percutaneous coronary intervention with bare-metal or drug-eluting stent implantation. All patients received a single 600-mg clopidogrel loading dose followed by 75 mg of clopidogrel daily and 100 to 325 mg of aspirin daily. The end points of the study at follow-up of 12 months were cardiovascular death, nonfatal myocardial infarction (MI), and target-vessel revascularization. At a 12-month follow-up, we found 51 ischemic events (24 cardiovascular
Reticulated platelets (RP) are newly-formed platelets with a greater mass, a residual amount of RNA and an increased prothrombotic potential. No studies investigating the association between RP and the risk of cardiovascular death in acute coronary syndrome (ACS) patients are available. In the frame of the AMI-Florence 2 study, we investigated RP in 229 (154 M/ 75 F) ACS patients (125 ST-elevation myocardial infarction [STEMI]; 104 Non-STEMI/Unstable Angina). RP were measured by using the Sysmex XE-2100 haematology analyzer and were expressed as the percentage of RP out of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (H-IPF). At one-year follow-up, 22 out of 229 patients (9.6%) died from cardiovascular causes. Higher values of IPF (p=0.05) and H-IPF (p=0.006) were detected in dead compared to alive patients. A receiver operating characteristics curve analysis identified IPF ≥3.3% and H-IPF ≥0.9% as optimal cut-off values to predict cardiovascular death. At the multivariate model adjusted for the Global Registry of Acute Coronary Events (GRACE) risk score, the association between RP and cardiovascular death remained significant for both IPF [OR (95%CI) : 4.15 (1.24-13.91) p=0.02] and H-IPF [OR (95%CI): H-IPF 5.03 (1.38-18.38) p=0.01]. In conclusion, RP are independent predictors of cardiovascular death and may be useful in improving risk stratification for ACS patients. Future prospective studies to evaluate the role of RP in determining cardiovascular events are warranted.
Summary. Background: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. Objectives and Methods: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5´-diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 lmol L -1 ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients. Results: Cut-off values for identifying RPR were: ‡ 54% and ‡ 66% for LTA induced by 2 and 10 lmol L -1 ADP respectively, and ‡ 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was ‡ 68 s. RPR was detected in 25.1% of patients by 2 lmol L -1 ADP-induced LTA (ADP-LTA), in 23.2% by 10 lmol L -1 ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (q = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 lmol L -1 ADP. The correlation was similar but the agreement was better between VerifyNow and 10 lmol L -1 ADP-LTA (q = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays. Conclusions: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.
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