Crushed Prasugrel Loading Dose Still No Benefit at 1 Year in COMPARE CRUSH

Some speculate that the effect of crushing tablets may become more apparent in regions with longer transfer delays to hospital.

Crushed Prasugrel Loading Dose Still No Benefit at 1 Year in COMPARE CRUSH

There is no benefit in terms of 1-year clinical outcomes for STEMI patients who receive crushed over integral prasugrel tablet loading doses in the ambulance, according to new data from the COMPARE CRUSH trial.

The findings follow the original trial results showing no improvement in reperfusion rates, as well as those from a follow-up study demonstrating faster and stronger platelet inhibition with crushed versus whole tablets.

Notably, COMPARE CRUSH was not powered to detect a difference in clinical outcomes, said Rosanne Vogel, MD (University Medical Center Utrecht, the Netherlands), who presented the findings as a “Key Abstract” online as part of a sneak peek at TCT 2021 and stressed the latest analysis looked at “a secondary endpoint” of the main study. “The real primary endpoint of the COMPARE CRUSH study was early myocardial reperfusion parameters: the TIMI 3 flow on angiography before PCI and the ST-segment resolution after PCI. Our trial cohort was powered to assess these two independent primary outcomes, and that’s why the cohort is not large enough to assess any clinical endpoints,” she explained.

Harlan Krumholz, MD (Yale University School of Medicine, New Haven, CT), in discussion following the study’s presentation, called this limitation “severe.” However, he said, “I really like the idea of a very pragmatic trial that’s asking very straightforward question that we have maybe prior beliefs about but don’t have good evidence for.”

Also commenting during the session, moderator Stephan Achenbach, MD (University of Erlangen, Germany), noted that the Netherlands, where the study took place, is a “small country” and speculated that the study findings might be different in another location where patients take longer to reach the hospital.

Vogel agreed, reporting that the median time in the ambulance during COMPARE CRUSH was about 45 minutes. “That’s not a very long period even for crushed medication to get working,” she said. “Therefore, we believe that if the transfer delay is increased, the crushing effect might become more apparent in this specific subgroup of patients.”

Prasugrel in the Ambulance

Of the 633 STEMI patients enrolled in the study, 326 and 288 patients who received crushed and integral prasugrel, respectively, completed 1-year follow-up. The researchers observed no differences with regard to the composite primary endpoints of death, MI, and urgent revascularization (P = 0.61) and of death, MI, urgent revascularization, stroke, and stent thrombosis (P = 0.65), or any of the individual components.

One-year survival was better in patients who achieved complete ST-segment resolution 1 hour following primary PCI (OR 0.16; 95% CI 0.03-0.72), although as noted this analysis lacked appropriate statistical power. No differences in MI, stent thrombosis, stroke, and unplanned revascularization were seen. There were also no differences in any clinical outcomes between the patients who had TIMI 3 flow in the infarct related artery pre-PCI and those who did not.

Given the exclusion criteria, Vogel added that the results cannot be generalizable to STEMI patients whose first medical contact was not in an ambulance, nor to those in cardiogenic shock.

Ultimately, the original study showed that giving crushed tablets as a loading dose for STEMI patients was safe, but “the present analysis indicates that there is also no improvement in 1-year clinical outcomes,” she concluded. “Whether new antithrombotic agents like selatogrel and [the subcutaneous small‐molecule platelet glycoprotein IIb/IIIa inhibitor] RUC-4 have the potential to improve early myocardial reperfusion in STEMI patients is currently under investigation in phase II clinical trials.”

Notably, both Achenbach as well as panelist Anuradha Tunuguntla, MBBS (CHI Health Nebraska Heart, Lincoln), said they do not pretreat STEMI patients at their institutions.

Sources
  • Vogel RF. Long-term efficacy of pre-hospital treatment with crushed versus integral tablets of prasugrel in patients presenting with STEMI: 1-year results from the randomized COMPARE CRUSH trial. Presented at: TCT 2021. October 13, 2021.

Disclosures
  • Vogel reports no relevant conflicts of interest.

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