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

Abstract

OBJECTIVES:

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).

BACKGROUND:

Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y12 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 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).

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.

• 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
• Journal: JACC. Cardiovascular interventions (JACC Cardiovasc Interv) Vol. 14 Issue 12 Pg. 1323-1333 (06 28 2021) ISSN: 1876-7605 [Electronic] United States
• PMID: 34167672 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Prasugrel Hydrochloride

Topics

• Hospitals
• Humans
• Myocardial Infarction (drug therapy)
• Percutaneous Coronary Intervention (adverse effects)
• Platelet Aggregation Inhibitors (adverse effects)
• Prasugrel Hydrochloride (adverse effects)
• Purinergic P2Y Receptor Antagonists (adverse effects)
• ST Elevation Myocardial Infarction (diagnostic imaging, drug therapy)
• Treatment Outcome