Giving crushed prasugrel tablets to patients presenting with ST-elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) did not improve Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the culprit artery during primary PCI in comparison with non-crushed tablets, according to study results presented Wednesday at the TCT Connect virtual conference.
George J. Vlachojannis, MD, of University Medical Center Utrecht, Den Haag, Netherlands, presented the results of the COMPARE CRUSH trial, which were also simultaneously published online in Circulation.
Guidelines currently recommend early treatment with a P2Y12 inhibitor in STEMI patients undergoing primary PCI, as this has been found to reduce intraprocedural and postprocedural ischemic complications. Degree of myocardial damage, post-PCI arterial flow and microvascular obstruction extent have been found to be associated with platelet reactivity. Crushed P2Y12 inhibitor tablets has been shown to increase the drug’s absorption and start platelet inhibition earlier than integral tablets.
In the COMPARE CRUSH study, patients presenting with STEMI where randomized in a 1-to-1 fashion to receive, while still in the ambulance, a loading dose (60 mg) of either crushed or non-crushed prasugrel and then taken to undergo primary PCI. Prasugrel tablets were crushed using a syringe crusher (Welcon, Fort Worth, Texas). All patients were additionally treated according to national ambulance STEMI protocol with 500 mg of aspirin and 5,000 international units of heparin, both administered intravenously.
The independent primary endpoints were TIMI 3 flow in the infarct-related artery at first angiography and ≥70% ST-segment resolution 1 hour after primary PCI. Key secondary endpoints included platelet reactivity; clinical outcomes including death, myocardial infarction (MI), urgent revascularization and stent thrombosis; and a safety endpoint, bleeding.
A total of 727 STEMI patients were enrolled and randomized to receive either integral or crushed prasugrel in the ambulance. The study population had an average age of 62 years, 23% were women, and 40% were active smokers. The median time from treatment to wire crossing was 57 minutes, and the most common MI was anterior; 93% of cases done via radial access.
The primary endpoint occurred in 31% of the crushed prasugrel group and 32.7% of the non-crushed prasugrel group (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.65-1.30; p=0.64). One-hour post-PCI, complete resolution of the ST segment elevation was present in 59.9% of the crushed group and 57.3% of the integral group (OR, 1.11; 95% CI, 0.78-1.58; p=0.55). There was a significant difference between the groups with respect to P2Y12 reactivity (crushed, 192 [95% CI, 132 – 245] vs. integral, 227 [95% CI, 184 – 254], p<0.01). There were no significant differences in TIMI major bleeding and Bleeding Academic Research Consortium ≥3 bleeding between the groups. Finally, ischemic events at 30 days were not significantly different between the groups.
Vlachojannis concluded by saying that TIMI 3 flow in the infarct related artery or 1 hour post-PCI ST-segment resolution were not improved with crushed prasugrel tablets compared to integral tables in patients with STEMI planned for primary PCI. This is in spite of more potent platelet inhibition with crushed prasugrel.
The question remains as to whether coronary reperfusion may be improved with the use of faster and more potent antiplatelet therapy in the setting of STEMI.