Crushed prasugrel prehospital fails to improve STEMI reperfusion vs. integral tablets
In the COMPARE CRUSH trial, administration of crushed prasugrel tablets in patients with STEMI on the way to the hospital planned for primary PCI did not improve coronary reperfusion.
COMPARE CRUSH enrolled 727 patients with STEMI who were randomly assigned to a 60 mg loading dose of prasugrel (Effient, Daiichi Sankyo/Eli Lilly) as crushed or integral tablets in the ambulance. The primary endpoint of TIMI 3 flow in the infarct-related artery at initial coronary angiography before PCI was similar in patients who received crushed prasugrel compared with those who received integral prasugrel tablets: 31% vs. 32.7% (OR = 0.92; 95% CI, 0.65-1.3). The trial’s coprimary endpoint, complete ST-segment resolution 1 hour after PCI, was reported in 59.9% of the crushed prasugrel group compared with 57.3% assigned integral prasugrel tablets (OR = 1.11; 95% CI, 0.78-1.58), George J. Vlachojannis, MD, with the division of heart and lungs at University Medical Center Utrecht, the Netherlands, said during a presentation at the virtual TCT Connect.
“These findings hold in spite of the fact that crushed tablets of prasugrel lead to more potent platelet inhibition compared with integral tablets,” Vlachojannis said during a press conference. “Whether faster and more potent antiplatelet therapy can improve coronary reperfusion in contemporary STEMI treatment regimen warrants further investigation.”
Platelet reactivity at the beginning of PCI was 192 P2Y12 reactivity units in the crushed prasugrel group compared with 227 P2Y12 reactivity units in the integral prasugrel tablets group (P < .01).
In other results, TIMI major bleeding did not occur in the crushed prasugrel group compared with 0.8% of the integral tablets group and Bleeding Academic Research Consortium (BARC) type 3 or greater bleeding in 0.2% vs. 1.1%, respectively.
Vlachojannis also reported no differences in ischemic events at 30 days.
COMPARE CRUSH was conducted in the Netherlands from November 2017 to February 2020. Researchers enrolled patients with symptoms of acute MI lasting no more than 6 hours and new persistent ST-segment elevation of 1 mm or greater. The mean age was 62 years and three-quarters were men. Median time from treatment to wire crossing during PCI was 57 minutes. Radial access was used in 94% of cases and more than 90% of patients received drug-eluting stents.
“Our data confirms improved pharmacodynamic profiles of oral P2Y12 inhibitors in STEMI patients by crushing tables. The faster inhibition and reduction in high platelet reactivity rates with crushed tablets is comparable with the results reported in prior investigations. Nevertheless, despite the treatment strategy applied in the present study ... a considerable number of STEMI patients experience levels of platelet reactivity above the thresholds associated with thrombotic events at the start of coronary angiography. Whether the neutral findings of the present study are due to the modest level of platelet inhibitor inhibition or to the choice of pharmacological target remains unknown,” the researchers wrote in Circulation.
Together, with other research, the COMPARE CRUSH researchers said the findings “underscore the need for alternative strategies to achieve faster and more potential platelet inhibition in patients undergoing primary PCI.”
Vlachojannis noted that the results of this trial “must be interpreted in the context of a robust STEMI network including short intervals between first medical contact and planned PCI and might not reflect routine practice around the world.”
Reference:
Collapse
Vlachojannis G, et al. Late-breaking clinical science session I, co-sponsored by Circulation. Presented at: TCT Connect; Oct. 14-18, 2020 (virtual meeting).