Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction |
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| Authors: | Rosanne F. Vogel Ronak Delewi Dominick J. Angiolillo Jeroen M. Wilschut Miguel E. Lemmert Roberto Diletti Ria van Vliet Nancy W.P.L. van der Waarden Rutger-Jan Nuis Valeria Paradies Dimitrios Alexopoulos Felix Zijlstra Gilles Montalescot Mitchell W. Krucoff Nicolas M. van Mieghem Pieter C. Smits Georgios J. Vlachojannis |
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| Affiliation: | 1. Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands;2. Department of Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands;3. Department of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA;4. Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands;5. Department of Cardiology, Isala Hospital, Zwolle, the Netherlands;6. Department of Cardiology, Maasstad Hospital, Rotterdam, the Netherlands;7. Emergency Medical Service, AmbulanceZorg Rotterdam-Rijnmond, Barendrecht, the Netherlands;8. Department of Cardiology, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece;9. Department of Cardiology, ACTION Group, Groupe Hospitalier Pitié-Salpêtrière Hospital (Assistance Publique-Hôpitaux de Paris), Sorbonne University, Paris, France;10. Department of Cardiology, Duke University Medical Center, Durham, North Carolina, USA |
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| Abstract: | ObjectivesThis study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).BackgroundEarly dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y12 inhibitor effect is delayed and varies according to formulation administered.MethodsThe 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.ResultsA 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 P2Y12 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).ConclusionsOral 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. |
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| Keywords: | crushing platelet reactivity pretreatment primary percutaneous coronary intervention ST-segment elevation myocardial infarction BMI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" body mass index HPR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" high platelet reactivity IQR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" interquartile range IRA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" infarct-related artery MACCE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" major adverse cardiac and cerebrovascular event PCI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" percutaneous coronary intervention PD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" pharmacodynamic pPCI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" primary percutaneous coronary intervention PRU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0125" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" __text__" ," _" :" P2Y" },{" #name" :" inf" ," $" :{" loc" :" post" }," _" :" 12" },{" #name" :" __text__" ," _" :" reactivity units STEMI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0135" }," $$" :[{" #name" :" text" ," _" :" ST-segment elevation myocardial infarction |
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