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

Publication ,  Journal Article
Vogel, RF; Delewi, R; Angiolillo, DJ; Wilschut, JM; Lemmert, ME; Diletti, R; van Vliet, R; van der Waarden, NWPL; Nuis, R-J; Paradies, V ...
Published in: JACC Cardiovasc Interv
June 28, 2021

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.

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Published In

JACC Cardiovasc Interv

DOI

EISSN

1876-7605

Publication Date

June 28, 2021

Volume

14

Issue

12

Start / End Page

1323 / 1333

Location

United States

Related Subject Headings

  • Treatment Outcome
  • ST Elevation Myocardial Infarction
  • Purinergic P2Y Receptor Antagonists
  • Prasugrel Hydrochloride
  • Platelet Aggregation Inhibitors
  • Percutaneous Coronary Intervention
  • Myocardial Infarction
  • Humans
  • Hospitals
  • Cardiovascular System & Hematology
 

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Vogel, R. F., Delewi, R., Angiolillo, D. J., Wilschut, J. M., Lemmert, M. E., Diletti, R., … Vlachojannis, G. J. (2021). Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv, 14(12), 1323–1333. https://doi.org/10.1016/j.jcin.2021.04.022
Vogel, Rosanne F., Ronak Delewi, Dominick J. Angiolillo, Jeroen M. Wilschut, Miguel E. Lemmert, Roberto Diletti, Ria van Vliet, et al. “Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction.JACC Cardiovasc Interv 14, no. 12 (June 28, 2021): 1323–33. https://doi.org/10.1016/j.jcin.2021.04.022.
Vogel RF, Delewi R, Angiolillo DJ, Wilschut JM, Lemmert ME, Diletti R, et al. Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2021 Jun 28;14(12):1323–33.
Vogel, Rosanne F., et al. “Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction.JACC Cardiovasc Interv, vol. 14, no. 12, June 2021, pp. 1323–33. Pubmed, doi:10.1016/j.jcin.2021.04.022.
Vogel RF, Delewi R, Angiolillo DJ, Wilschut JM, Lemmert ME, Diletti R, van Vliet R, van der Waarden NWPL, Nuis R-J, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Krucoff MW, van Mieghem NM, Smits PC, Vlachojannis GJ. Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2021 Jun 28;14(12):1323–1333.
Journal cover image

Published In

JACC Cardiovasc Interv

DOI

EISSN

1876-7605

Publication Date

June 28, 2021

Volume

14

Issue

12

Start / End Page

1323 / 1333

Location

United States

Related Subject Headings

  • Treatment Outcome
  • ST Elevation Myocardial Infarction
  • Purinergic P2Y Receptor Antagonists
  • Prasugrel Hydrochloride
  • Platelet Aggregation Inhibitors
  • Percutaneous Coronary Intervention
  • Myocardial Infarction
  • Humans
  • Hospitals
  • Cardiovascular System & Hematology