TY - JOUR
T1 - Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction
AU - Vogel, Rosanne F.
AU - Delewi, Ronak
AU - Angiolillo, Dominick J.
AU - Wilschut, Jeroen M.
AU - Lemmert, Miguel E.
AU - Diletti, Roberto
AU - van Vliet, Ria
AU - van der Waarden, Nancy W. P. L.
AU - Nuis, Rutger-Jan
AU - Paradies, Valeria
AU - Alexopoulos, Dimitrios
AU - Zijlstra, Felix
AU - Montalescot, Gilles
AU - Krucoff, Mitchell W.
AU - van Mieghem, Nicolas M.
AU - Smits, Pieter C.
AU - Vlachojannis, Georgios J.
N1 - Funding Information:
The COMPARE CRUSH trial was funded by Maasstad Research B.V. (Rotterdam, the Netherlands), which received unrestricted grants from Daiichi-Sankyo and Shanghai MicroPort Medical. The funding companies were not involved in the conduct of the trial, the analysis of the data, or the drafts of the manuscripts. Dr. Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St. Jude Medical; and has received institutional research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr. Alexopoulos has received consulting fees or honoraria from AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Chiesi Hellas, Medtronic, and Pfizer. Dr. Montalescot has received research or institutional grant support or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CellProthera, Europa, IRIS-Servier, Novartis, Medtronic, MSD, Pfizer, Quantum Genomics, and Sanofi. Dr. Van Mieghem has received institutional research grant support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, Teleflex, PulseCath BV, and Daiichi-Sankyo. Dr. Smits has received research grant support from Daiichi-Sankyo and Shanghai MicroPort. Dr. Vlachojannis has received consulting fees from AstraZeneca; and research grant support from Daiichi-Sankyo and Shanghai MicroPort. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Funding Information:
The authors thank the team of the regional ambulance service ?AmbulanceZorg Rotterdam-Rijnmond? and their medical director M. Biekart, and the catheterization laboratories and cardiac care units of Maasstad Hospital and Erasmus Medical Center. Furthermore, the authors thank the members of the data monitoring and safety board, F.W.A. Verheugt, J.G.P. Tijssen, and M. Voskuil;? the members of the clinical event adjudication committee, K.T. Koch and M. Meuwissen; and the members of the ST-segment elevation myocardial infarction adjudication committee, F. Nijhoff and M. Grundeken. Moreover, the authors thank C. Vliet, A. Ruiter, and R. van Dam for clinical data acquisition. Last, the authors thank J. Uiters (Medwave), Vaglio and F. Badilini (AMPS LLC), and Lennard L.P.J. Kuijten (data science and analytics specialist) for their active support of the trial.
Publisher Copyright:
© 2021 American College of Cardiology Foundation
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/28
Y1 - 2021/6/28
N2 - Objectives: This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y
12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Background: Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y
12 inhibitor effect is delayed and varies according to formulation administered. Methods: The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion. Results: A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y
12 reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40). Conclusions: Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.
AB - Objectives: This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y
12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Background: Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y
12 inhibitor effect is delayed and varies according to formulation administered. Methods: The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion. Results: A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y
12 reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40). Conclusions: Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.
KW - P2Y inhibitors
KW - ST-segment elevation myocardial infarction
KW - crushing
KW - platelet reactivity
KW - pretreatment
KW - primary percutaneous coronary intervention
UR - https://www.scopus.com/pages/publications/85107739426
U2 - 10.1016/j.jcin.2021.04.022
DO - 10.1016/j.jcin.2021.04.022
M3 - Article
C2 - 34167672
SN - 1936-8798
VL - 14
SP - 1323
EP - 1333
JO - JACC. Cardiovascular interventions
JF - JACC. Cardiovascular interventions
IS - 12
ER -
SDG 3 Good Health and Well-being