From tablet to powder: Crushed prasugrel no help in STEMI reperfusion

Crushing prasugrel tablets and administering it as a powder to patients with ST-segment elevation myocardial infarction (STEMI) prior to percutaneous coronary intervention (PCI) enhances the potency of platelet inhibition but fails to improve early coronary reperfusion, as shown in the results of the COMPARE CRUSH trial.

A main drawback of oral P2Y12 receptor inhibitors in STEMI is the slow onset of platelet inhibition due to diminished drug absorption, leading to decreased bioavailability, according to the investigators. [Nat Rev Cardiol 2017;14:361-379]

“Our data confirms improved pharmacodynamic profiles of oral P2Y12 inhibitors in STEMI patients… The faster platelet inhibition and reduction in high platelet reactivity (HPR) rates with crushed tablets [192 vs 227 with whole tablets; p≤0.01] is comparable with the results reported in prior investigations,” they noted. [J Am Coll Cardiol 2015;65:511-512; J Am Coll Cardiol 2016;67:1994-2004]

“Nevertheless, despite the treatment strategy applied in the present study (ie, prehospital administration of crushed prasugrel loading dose), a considerable number of STEMI patients experience levels of platelet reactivity above the thresholds associated with thrombotic events at the start of coronary angiography,” they added.

A total of 727 STEMI patients (average age, 62 years; 23 percent female) were randomized to receive either crushed or whole tablets of prasugrel loading dose of 60 mg. Antiplatelet was administered in the ambulance on their way to the hospital for primary PCI. All patients were also given aspirin (500 mg) and heparin (5,000 international units) intravenously.

The median time from study treatment to PCI was 57 minutes. The primary endpoint of thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery (IRA) prior to PCI occurred in a similar number of patients in the crushed and integral tablet groups (31.0 percent vs 32.7 percent; odds ratio [OR], 0.92, 95 percent confidence interval [CI], 0.65–1.30; p=0.64). [Circulation 2020;doi:10.1161/CIRCULATIONAHA.120.051532]

Likewise, there was no significant difference noted in the achievement of complete ST-segment resolution 1 hour after PCI (59.9 percent in the crushed group vs 57.3 percent in the integral group; OR, 1.11, 95 percent CI, 0.78–1.58; p=0.55).

Safety was similar in the crushed and integral groups. Comparable TIMI major and BARC ≥3 bleeding events occurred in the first 48 hours (0 percent vs 0.8 percent and 0.3 percent vs 1.1 percent, respectively) and at 30 days (0.3 percent vs 1.0 percent and 1.2 percent vs 2.0 percent, respectively).

“It appears unlikely that oral P2Y12 inhibitors will be able to bridge the gap in platelet inhibition in STEMI patients undergoing primary PCI,” according to the investigators.

Then again, they asserted that early initiation of potent antiplatelet therapy in STEMI patients remains the cornerstone of therapy to minimize intra- and early postprocedural ischaemic complications, including stent thrombosis.

“Whether faster and more potent platelet inhibition with parenteral antiplatelet agents—on the background of contemporary STEMI treatment regimen—can improve early coronary reperfusion and clinical outcomes without excess in bleeding complications warrants investigation,” the investigators said.