Pre-hospital treatment with crushed prasugrel tablets was not found to improve thrombolysis in myocardial infarction (TIMI) 3 flow among patients with ST-segment elevation myocardial infarction (STEMI) scheduled to undergo primary percutaneous coronary intervention (pPCI), according to study results published in the American Heart Journal.

In this controlled, multicenter study, 277 patients (mean age, 62 years; 23% women; 40% smokers; 15% with diabetes mellitus) with STEMI undergoing pPCI at 2 centers in the Netherlands between 2017 and 2020 were randomly assigned to receive orally 60 mg prasugrel in the crushed form (n=96) or as an integral tablet (n=92). Patients also received 500 mg aspirin and 5000 international units of heparin intravenously.

The study’s primary endpoints were TIMI 3 flow in affected artery and complete ST-segment resolution (ie, ≥70%) 1 hour after pPCI. Safety endpoints were occurrence of bleeding and TIMI major, both assessed with the bleeding academic research consortium (BARC) score.


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Radial artery access was used in the majority of patients (93%). pPCI was performed in 97% of study participants,  96% of whom received a drug eluting stent, and 12% were administered peri-procedural glycoprotein inhibitors. Median time between symptom onset, study treatment, and pPCI did not differ between treatment groups.

TIMI 3 flow in the infarct-related artery was observed in 31.0% and 32.7% of patients in the crushed and tablet groups, respectively (odds ratio [OR], 0.92; 95% CI, 0.65-1.30; P =.64). TIMI 3 flow was significantly improved in patients given crushed tablets with a history of a previous PCI (P <.001), anterior infarction (P =.03), or those ages ³75 years (P =.04).

Platelet reactivity was reduced in patients in the crushed vs integral tablet group (P2Y12 reactivity units: 192; 95% CI, 132-245 vs 227, respectively; 95% CI, 184-254; P <.01). This reduction resulted in a lower percentage of patients with high platelet reactivity at the beginning of coronary angiography (crushed: 43.3% vs tablet: 62.6%; P <.01).

At 1-hour post-pPCI, complete ST-segment resolution was achieved by 59.9% and 57.3%  of participants in the crushed and integral tablet groups, respectively (OR, 1.11; 95% CI, 0.78-1.58; P =.55).

At 30 days post pPCI, the rates of a composite of myocardial reinfarction, urgent revascularization, or death were not different between crushed (4.3%) or tablet (3.7%) groups (OR, 1.16; 95% CI, 0.52-2.59; P =.84). Patients receiving crushed and integral tablets had comparable rates of BARC ³3 (0.4% vs 0.7%, respectively) and TIMI major bleed (0% vs 0.8%, respectively) in the 48 hours following administration.

Study limitations include the absence of a placebo group, however, data were analyzed by blinded independent core laboratories in the attempt to avoid introducing additional bias.

“Pre-hospital administration of crushed tablets prasugrel LD in patients with STEMI planned for pPCI is not associated with improvement of TIMI 3 flow in the [infarct-related artery] at initial angiography or complete ST-segment resolution one hour after pPCI,” concluded the study authors.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Vlachojannis G J, Wilschut J M, Vogel R F, et al. Effect of pre-hospital crushed prasugrel tablets in patients with STEMI planned for primary percutaneous coronary intervention: The randomized COMPARE CRUSH trial. Am Heart J. 2020;224:10-16. doi:10.1016/j.ahj.2020.03.005