Potent P2Y12 inhibitor monotherapy without aspirin early after percutaneous coronary intervention: the NEO-MINDSET Platelet Function Substudy
P Guimaraes, T P Oliveira, M Franken, C A M Tavares, F G Pitta, J C C Guerra, R M C Penteado, V F Aranda, F Monfardini, G P Santos, M R Fonseca, J C Nicolau, M Valgimigli, D Angiolillo, P A LemosAbstract
Background
Few data are available on platelet reactivity in patients exposed to potent P2Y12 inhibitor monotherapy without aspirin.
Methods
This study was nested within the NEO-MINDSET trial, a multicenter, randomised trial evaluating potent P2Y12 inhibitor monotherapy early after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) compared with dual antiplatelet therapy (DAPT). In both groups, only prasugrel or ticagrelor were allowed, which were chosen at investigator discretion. This substudy aimed to assess treatment effects on platelet reactivity. Patients recruited at the coordinating site were eligible. Blood samples were collected pre-dose (trough) and 2-hour post-morning-dose (peak) at a single follow-up visit occurring after at least 30 days of exposure to the assigned treatment. Platelet reactivity was assessed by Platelet Function Analyzer-200 (PFA-200), VerifyNow, light transmittance aggregometry, and impedance aggregometry. Antiplatelet effects between study groups were assessed using linear mixed model for repeated measures.
Results
A total of 44 trial participants were enrolled: 22 assigned to monotherapy and 22 to DAPT. Mean age was 56.5 years and 36.4% were women. In each group, 16 (72.7%) received prasugrel and 6 (27.3%) received ticagrelor. The median time from randomization to platelet analysis was 183 days (interquartile range 36.8 to 202.5). In the monotherapy group, the mean platelet responses to collagen/epinephrine or arachidonic acid were within or close to the normal range at both trough and peak (Figures). In the DAPT group, platelet function was consistently inhibited with collagen/epinephrine or arachidonic acid at pre- and post-dose. In both groups, no significant increment in platelet inhibition was seen between pre-dose and post-dose values. Using collagen/ADP or ADP as agonists, results indicated platelet inhibition at both trough and peak in patients receiving monotherapy or DAPT. In the monotherapy group, greater platelet inhibition was achieved post-dose compared with pre-dose in PFA-200 (128.8 vs 161.7 seconds; p=0.04), VerifyNow (53.5 vs 24.7 PRU; p=0.003), and light transmission aggregometry (21.3% vs 11.9%; p=0.006). In the DAPT group, peak effects were observed in PFA-200 (228.9 vs 275.4 seconds; p=0.005) and VerifyNow (53.6 vs 27.1; p=0.003). Patients receiving monotherapy compared with DAPT had similar antiplatelet responses to ADP and smaller responses to arachidonic acid, collagen/epinephrine and collagen/ADP (all p-values < 0.01).
Conclusions
Among patients undergoing successful PCI for ACS receiving monotherapy without aspirin, platelet function was inhibited in response to ADP at both pre- and post-dose, which suggests that potent P2Y12 inhibitor effects are preserved at trough. Conversely, platelet inhibition was greater with DAPT than monotherapy when agonists targeted to the cyclooxygenase-1 pathway were used.Figure 1Figure 2