Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction

Published on Jun 28, 2021in Jacc-cardiovascular Interventions8.432
· DOI :10.1016/J.JCIN.2021.04.022
Rosanne F. Vogel2
Estimated H-index: 2
(UU: Utrecht University),
Ronak Delewi24
Estimated H-index: 24
(UvA: University of Amsterdam)
+ 14 AuthorsValeria Paradies15
Estimated H-index: 15
Abstract null null Objectives null This 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). null null null Background null Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y12 inhibitor effect is delayed and varies according to formulation administered. null null null Methods null 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. null null null Results null 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  null null null Conclusions null 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.
📖 Papers frequently viewed together
28 Citations
36 Citations
24 Citations
#1Georgios J. Vlachojannis (UU: Utrecht University)H-Index: 12
#2Jeroen Wilschut (EUR: Erasmus University Rotterdam)H-Index: 9
Last. Pieter C. SmitsH-Index: 44
view all 16 authors...
Background: Early treatment with a potent oral platelet P2Y12 inhibitor is recommended in patients presenting with ST-segment elevation myocardial infarction (STEMI) planned to undergo primary perc...
11 CitationsSource
#1Giuseppe Gargiulo (University of Naples Federico II)H-Index: 26
#2Giovanni Esposito (University of Naples Federico II)H-Index: 72
Last. Marco Valgimigli (University of Bern)H-Index: 117
view all 17 authors...
Background: Standard administration of newer oral P2Y12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in ST-segment elevation myo...
18 CitationsSource
#1Anne H. TavenierH-Index: 3
Last. A. W. J. van ’t Hof (Maastricht University Medical Centre)H-Index: 4
view all 21 authors...
AIM Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI. METHODS AND RESULTS The ON-TIME 3 trial randomised 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated ...
9 CitationsSource
#1Georgios J. Vlachojannis (UU: Utrecht University)H-Index: 10
#1Georgios J. Vlachojannis (UU: Utrecht University)H-Index: 12
Last. Pieter C. SmitsH-Index: 44
view all 17 authors...
Abstract Background Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves ...
4 CitationsSource
#1Peter Sinnaeve (Katholieke Universiteit Leuven)H-Index: 40
#2Gregor Fahrni (University of Basel)H-Index: 7
Last. Marco Valgimigli (University of Bern)H-Index: 117
view all 12 authors...
Abstract Background Oral P2Y12 receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y12 receptor antagonist with a rapid onset and short duration of action. Objectives This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI. Methods Patients with AMI were randomized to a single subcutaneous dose...
19 CitationsSource
#1Jean-Sébastien Hulot (University of Paris)H-Index: 65
#2Gilles Montalescot (University of Paris)H-Index: 111
3 CitationsSource
#1Dirk SibbingH-Index: 41
#2Daniel Aradi (Semmelweis University)H-Index: 19
Last. Dominick J. Angiolillo (UF: University of Florida)H-Index: 106
view all 26 authors...
Highlights •Different P2Y12 inhibitors have enabled physicians to contemplate individualized treatment regimens. •In selective scenarios, PFT and genotyping may be used as optional tools for guiding treatment. •Further studies on DAPT de-escalation and escalation are needed to refine existing treatment options.
149 CitationsSource
#1Björn Redfors (Sahlgrenska University Hospital)H-Index: 28
#1Björn Redfors (Sahlgrenska University Hospital)H-Index: 5
Last. Elmir Omerovic (Sahlgrenska University Hospital)H-Index: 36
view all 14 authors...
AIMS: Pretreatment of patients with ST-elevation myocardial infarction (STEMI) with P2Y12 receptor antagonists is supported by guidelines and is a common practice despite the lack of definite evidence for its benefit. METHODS AND RESULTS: Using data from the Swedish Coronary Angiography and Angioplasty Registry on procedures between 2005 and 2016, we stratified all patients who underwent primary percutaneous coronary intervention due to STEMI in Sweden by whether or not they were pretreated with...
10 CitationsSource
#1Francesco Franchi (UF: University of Florida)H-Index: 26
#2Fabiana Rollini (UF: University of Florida)H-Index: 23
Last. Dominick J. AngiolilloH-Index: 106
view all 18 authors...
Background: The platelet inhibitory effects induced by oral P2Y12 receptor antagonists are delayed in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous corona...
57 CitationsSource
#1Davide Capodanno (University of Catania)H-Index: 74
#2Fernando AlfonsoH-Index: 85
Last. Dominick J. Angiolillo (UF: University of Florida)H-Index: 106
view all 5 authors...
Abstract Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacological treatment aimed at preventing the atherothrombotic complications in patients with a variety of coronary artery disease (CAD) manifestations. Prescribers of DAPT are confronted with a number of challenges that include selecting the appropriate P2Y12 inhibitor and determining the optimal duration of DAPT with the scope of minimizing the risk of ischemic and bleeding complications in light of each patient’s clinical cha...
122 CitationsSource
Cited By1
#1Arka Chatterjee (UA: University of Arizona)H-Index: 1
#1Arka Chatterjee (UA: University of Arizona)H-Index: 50
Last. DO Kristina Skinner (UA: University of Arizona)
view all 2 authors...