Ticagrelor plasma concentration. Observed and predicted plasma concentrations (A) and relationship with number of vaso-occlusive crises (VOCs) (B). Observed and predicted platelet inhibition (C) and relationship with platelet reactivity index (D). As shown in panels A and C, predicted plasma concentrations based on HESTIA1 and HESTIA2: green line is the median, and the green area is the 5% to 95% quantiles. Because ticagrelor is given every 12 hours, the 12 hours’ postdose time point is also the immediate predose (or trough) time point. As shown in panel B, individual geometric mean ticagrelor plasma concentration at visits 2, 4, and 9: blue line is the negative binomial regression model. As shown in panel D, time-matched platelet reactivity index and ticagrelor plasma concentrations, all visits: blue line is the exposure–response model of the maximum effect the drug can have.