Crushed prasugrel given to ST-elevation myocardial infarction (STEMI) patients in the ambulance did not lead to significantly improved markers for early reperfusion as compared to non-crushed prasugrel, according to an analysis presented Friday at CRT 2021 Virtual.
Rosanne F. Vogel, MD, of University Medical Center Utrecht, Netherlands, presented this analysis, a substudy of the COMPARE CRUSH trial, as an abstract at CRT. The main COMPARE CRUSH results were published in December in Circulation.
STEMI patients show high levels of platelet reactivity because of reduced bioavailability in the first hours after antiplatelet therapy is started with percutaneous coronary intervention (PCI). This increased platelet reactivity is associated with an increased risk of thrombotic events. The question COMPARE CRUSH sought to answer was whether prehospital crushed prasugrel improved the bioavailability of oral antiplatelet agents in STEMI patients.
The trial randomized 727 patients in the Netherlands to a 60-mg loading dose of either crushed or integral prasugrel in the ambulance. Prasugrel tablets were crushed using a syringe crusher (Welcon, Fort Worth, Texas). The study showed no difference in its co-primary endpoints between the crushed or integral groups: Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery at first angiography and ≥70% ST-segment resolution 1 hour after primary PCI.
For the pharmacodynamic analysis presented Friday, blood samples were collected from the patients at baseline, the beginning of coronary angiography, the end of primary PCI and 4 hours after study treatment initiation. Patients with at least three platelet reactivity measurements were included in the analysis.
Of the 441 patients included, 235 received crushed prasugrel and 206 received integral tablets. Patients in the crushed-prasugrel group were younger (mean age 61±12 years vs. 63±12 years) with a higher rate of diabetes mellitus (18% vs. 12%) and a lower rate of dyslipidemia (19% vs. 26%).
At all time points, the rate of high platelet reactivity (HPR) was lower in the crushed-prasugrel group. Notably, Vogel pointed out, the crushed-prasugrel group showed 35% HPR at the end of primary PCI, which was significantly lower than the approximately 60% rate in the whole-tablet group.
The analysis also showed that HPR at the beginning of coronary angiography correlated with less TIMI 3 flow before primary PCI. However, despite HPR being lower in the crushed-prasugrel group, this did not translate into a significant difference in TIMI 3 flow before primary PCI or in any notable difference in the resolution of ST-segment elevation 1 hour after primary PCI.
The study’s limitations include not being powered for clinical endpoints, the absence of pharmacokinetic data, short time intervals (79 minutes from first medical contact [ambulance] to wire crossing), and that it is not applicable in patients with cardiogenic shock or cardiac arrest.
Vogel concluded that prehospital crushed prasugrel reduced HPR in STEMI patients as compared with integral prasugrel but that this did not improve markers of early myocardial reperfusion. A considerable number of STEMI patients still show HPR when primary PCI is about to begin. And HPR at the beginning of angiography correlates with a twofold lower chance of having TIMI 3 flow in the infarct-related artery before primary PCI.
“Crushing prehospital administered prasugrel did not translate into a significant improvement in markers of early myocardial reperfusion,” Vogel said. “More potent subcutaneous or parenteral antiplatelet agents might be able to provide maximal platelet inhibition in the first hours of treatment. Whether earlier platelet inhibition does translate into improved early myocardial reperfusion warrants further investigation.”
CRT 2021 Virtual takes place Fridays and Saturdays through April 24. On-demand content from the meeting is available here.