P2Y12 Reaction Units and Clinical Outcomes in Acute Large Artery Atherosclerotic Stroke: A Multicenter Prospective Study

Figures

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  Fig.1. Flowchart of patient participation in the study. AIS/TIA, Acute ischemic stroke or transient ischemic attack; PRU, P2Y12 reaction units.

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  Fig.2. Multivariable receiver operating characteristic curves and scatter plot showing the relationship between P2Y12 reaction units at 24 hours and recurrence (n=194). Multivariable receiver operating characteristic curves depicting predictive performance of the P2Y12 reaction units (PRU) assays for recurrence within 90 days (A), within 7 days (B), and during 8–90 days (C). Scatter plot showing correlation between PRU and the number of days to recurrence (D). Black squares show a value of PRU at 24 hours in the CYP2C19 poor metabolizer (PM) group. Empty circles show a value of PRU at 24 hours in the CYP2C19 extensive or intermediate metabolizer (EM/IM) group.

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  Supplemental Fig.1. The association between P2Y12 reaction units and possible influencing factors of clopidogrel responsiveness in patients undergoing genetic testing and receiving clopidogrel loading dose (n=121). In the group of 121 patients undergoing genetic testing and receiving clopidogrel loading dose, the association between PRU and possible factors influencing platelet reactivity was analyzed. In univariable analysis, PRU at 24 hours was significantly higher in the patients treated with proton pump inhibitors (PPIs) on admission than those not (221.1±59.9 versus 185.1±80.4; p=0.04). There was no significant difference in PRU at 24 hours between the three types of PPIs: (i) rabeprazole, (ii) esomeprazole/omeprazole, and lansoprazole, (iii) (299.5±0.71, 0.10, 228.6±62.7, versus 218.7±59.0). Furthermore, PRU at 24 hours tended to be higher in patients over 70 years (222.1±65.3 versus 201.3±66.0; p=0.09) and in the order of PM, IM, and EM for CYP2C19 (242.9±77.2, 217.6±60.9, and 189.5±68.0, respectively). In multivariable logistic regression analysis adjusted for the possible influencing factors with a p value ＜0.05 in the crude analysis or clinical significance (PM of CYP2C19, age over 70 years, and PPIs at the treatment starting point), PM of CYP2C19 (adjusted OR, 3.77; 95% CI, 1.11–12.86; p=0.034), age over 70 years (adjusted OR, 2.46; 95% CI, 1.02–5.93; p=0.045), and PPIs (adjusted…

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  Supplemental Fig.2. The association between P2Y12 reaction units and clopidogrel loading. In the group of 212 patients undergoing PRU evaluation at 24 and 72 hours after initiation of antiplatelet therapy and receiving newly administered loading dose (300 mg) or newly administered standard dose (75 mg) of clopidogrel, the association between PRU and clopidogrel loading was analyzed using by Wilcoxon rank-sum test. Patients with clopidogrel loading showed a significantly higher mean value of PRU at 24 hours compared with those without clopidogrel loading (213.0±72.6 versus 235.3±65.1; P=0.008). In contrast, there was no significant difference in PRU at 72 hours between the two groups (201.1±79.0 versus 210.2±85.4; p=0.53).