The value of platelet function testing (PFT) in predicting clinical outcomes and guiding
P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS
trial, we assessed ischaemic and bleeding risks according to high platelet reactivity
(HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel
vs. PFT-guided clopidogrel or prasugrel.Acute coronary syndrome patients with PFT
done 14 days after hospital discharge were included with prior randomization to uniform
prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation
from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back
to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular
death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic
Research Consortium (BARC) 2-5 bleeding, from PFT until 12 months. We identified 2527
patients with PFT results available: 1266 were randomized to the guided and 1261 to
the control group. Before treatment adjustment, HPR was more prevalent in the guided
group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%).
Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes
were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR):
1.06 (0.57-1.95), P = 0.86] and also in patients with HPR on clopidogrel switched
to prasugrel [n = 511, HR: 0.96 (0.47-1.96), P = 0.91]. In contrast, HPR on prasugrel
was associated with a higher risk for ischaemic events in control patients [n = 188,
HR: 2.16 (1.01-4.65), P = 0.049]. Low platelet reactivity was an independent predictor
of bleeding [HR: 1.74 (1.18-2.56), P = 0.005], without interaction (Pint = 0.76) between
study groups.Based on this substudy of a randomized trial, selecting prasugrel or
clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel
therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased
risk of ischaemic events. Low platelet reactivity was a strong and independent predictor
of bleeding both on prasugrel and clopidogrel.
