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IN VITRO PHARMACODYNAMIC EFFECTS OF CANGRELOR ON PLATELET P2Y12 RECEPTOR MEDIATED SIGNALING IN TICAGRELOR TREATED PATIENTS
213 JACC April 5, 2016 Volume 67, Issue 13
ACC.i2 Interventional Cardiology IN VITRO PHARMACODYNAMIC EFFECTS OF CANGRELOR ON PLATELET P2Y12 RECEPTOR MEDIATED SIGNALING IN TICAGRELOR TREATED PATIENTS Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 9:45 a.m.-10:30 a.m. Session Title: Anti Thrombotic New Theraputic Approaches Abstract Category: 1. ACC.i2 Interventional Cardiology: ACS/AMI/Hemodynamics and Pharmacology Presentation Number: 1174-129 Authors: Fabiana Rollini, Francesco Franchi, Estela Thano, Gabriel Faz, Yongwhi Park, Jenny Hu, Megha Kureti, Niti Aggarwal, Ashwin Durairaj, Jung Rae Cho, Latonya Been, Zeina Alobaidi, Martin Zenni, Theodore Bass, Dominick Angiolillo, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA Background: Variability in the onset of platelet inhibitory effects induced by oral P2Y12 receptor antagonists, including ticagrelor, has been shown in high-risk settings. These findings underscore the need for intravenous P2Y12 inhibiting therapies, such as cangrelor, with immediate effects. However, to date there are no pharmacodynamic (PD) studies of cangrelor in ticagrelor-treated patients, with and without a reloading regimen, which represented the aim of this investigation.
Methods: This was a prospective study conducted in patients (n=60) on ticagrelor 90mg bid maintenance therapy after an acute coronary syndrome who were randomized to receive either a 90mg or 180mg reload of ticagrelor. PD assessments were conducted before and after in vitro incubation with cangrelor (500 nM) at 3 time points: baseline, 1 hour and 4 hours after reload. PD assessments included P2Y12 reaction units (PRU) by VerifyNow, platelet reactivity index (PRI) by VASP, and platelet aggregation by LTA. Results: In vitro cangrelor significantly reduced PRI values at all time points in both patients reloaded with 90mg and 180mg of ticagrelor (Figure). After incubation with cangrelor, PRI levels were constantly low and similar irrespective of ticagrelor dosing regimen. Results were consistent with VerifyNow and LTA.
Conclusions: In patients on maintenance ticagrelor therapy exposed to a reloading dose (90 or 180mg) of ticagrelor, in vitro cangrelor is associated with promptly enhanced platelet P2Y12 receptor inhibition.
ACC.i2 Interventional Cardiology IN VITRO PHARMACODYNAMIC EFFECTS OF CANGRELOR ON PLATELET P2Y12 RECEPTOR MEDIATED SIGNALING IN TICAGRELOR TREATED PATIENTS Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 9:45 a.m.-10:30 a.m. Session Title: Anti Thrombotic New Theraputic Approaches Abstract Category: 1. ACC.i2 Interventional Cardiology: ACS/AMI/Hemodynamics and Pharmacology Presentation Number: 1174-129 Authors: Fabiana Rollini, Francesco Franchi, Estela Thano, Gabriel Faz, Yongwhi Park, Jenny Hu, Megha Kureti, Niti Aggarwal, Ashwin Durairaj, Jung Rae Cho, Latonya Been, Zeina Alobaidi, Martin Zenni, Theodore Bass, Dominick Angiolillo, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA Background: Variability in the onset of platelet inhibitory effects induced by oral P2Y12 receptor antagonists, including ticagrelor, has been shown in high-risk settings. These findings underscore the need for intravenous P2Y12 inhibiting therapies, such as cangrelor, with immediate effects. However, to date there are no pharmacodynamic (PD) studies of cangrelor in ticagrelor-treated patients, with and without a reloading regimen, which represented the aim of this investigation.
Methods: This was a prospective study conducted in patients (n=60) on ticagrelor 90mg bid maintenance therapy after an acute coronary syndrome who were randomized to receive either a 90mg or 180mg reload of ticagrelor. PD assessments were conducted before and after in vitro incubation with cangrelor (500 nM) at 3 time points: baseline, 1 hour and 4 hours after reload. PD assessments included P2Y12 reaction units (PRU) by VerifyNow, platelet reactivity index (PRI) by VASP, and platelet aggregation by LTA. Results: In vitro cangrelor significantly reduced PRI values at all time points in both patients reloaded with 90mg and 180mg of ticagrelor (Figure). After incubation with cangrelor, PRI levels were constantly low and similar irrespective of ticagrelor dosing regimen. Results were consistent with VerifyNow and LTA.
Conclusions: In patients on maintenance ticagrelor therapy exposed to a reloading dose (90 or 180mg) of ticagrelor, in vitro cangrelor is associated with promptly enhanced platelet P2Y12 receptor inhibition.