Crushed Prasugrel Prior to PCI Provides No Reperfusion Benefit in STEMI Patients

George Vlachojannis, MD

Despite observations from previous studies, results of the COMPARE CRUSH study found no benefit from crushed prasugrel prior to percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).

Presented at Transcatheter Cardiovascular Therapies (TCT) 2020, results of the study suggests patients experienced a greater degree of platelet inhibition as a result of crushed prasugrel, but this did not lead to any reperfusion effects in this patient population.

“Whether faster and more-potent antiplatelet therapy can improve coronary reperfusion in contemporary STEMI treatment regimen warrants further investigation,” said study presenter Georgios J. Vlachojannis, MD, of the University Medical Center Utrecht in the Netherlands, during a press briefing.

With previous studies, such as CRUSH, purporting a potential benefit of crushed prasugrel, the COMPARE CRUSH study was designed to further assess the potential benefit of crushed prasugrel in a randomized trial. Conducted at a pair of interventional centers in the Netherlands between 2017 and 2019, the trial enrolled more than 700 patients who were randomized in a 1:1 ratio to a 60 mg dose of crushed or integral tablets of prasugrel before transfer from the ambulance to the hospital.

The study included all consecutive patients with suspected STEMI and onset within 6 hours who were initially managed by a mobile emergency medical care unit and planned for PCI. Patients were excluded for the study if they had a history of a cerebral vascular accident, recent gastrointestinal bleeding, recent major surgery, an indication for chronic oral anticoagulation therapy, were dependent on hemodialysis, unable to swallow oral medication, or presented with cardiogenic shock or cardiac arrest.

Of note, the study required all patients to be treated with aspirin and heparin, as per national STEMI protocol. Patients were recommended to dual antiplatelet therapy with aspirin and prasugrel for 12 months following PCI.

The primary end points of the study were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography and complete ST-segment resolution 1-hour post-PCI. The safety end points for the study were TIMI major and bleeding academic research consortium (BARC) level 3 or greater bleeding. Investigators also included platelet reactivity and ischemic outcomes as secondary end points of the trial.

In total, 727 patients were randomized in the trial and the median time from study treatment to wire-crossing during PCI was 57 (47-70) minutes. For the primary end point, investigators found the TIMI 3 flow in the IRA pre-PCI occurred in 31% of patients in the crushed group and 32.7% of patients in the integral group (OR, 0.92; 95% CI, 0.65-1.30; P=.64). Complete ST-segment resolution 1-hour post-PCI was present among 59.9% of the crush group and 57.3% of the integral group (OR, 1.11; 95% CI, 0.78-1.58; P=.55).

When assessing platelet reactivity, which was measured through P2Y12 reactivity units, differed significantly between the study group (crushed: 192 [132-245] vs integral: 227 [184-254]; P <.01). For safety end points, investigators noted TIMI major and BAERC level 3 or greater bleeding occurred in 0% of the crushed group and 0.8% of the integral group and in 0.3% of the crushed group and 1.1% of the integral group, respectively. Additionally, investigators noted there were no differences between the groups when examining ischemic events at 30 days.

This study, “Effect of Pre-Hospital Crushed Prasugrel Tablets in Patients with STEMI Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial,” was presented at TCT 2020 and published simultaneously in Circulation.