Do Crushed Prasugrel Tablets Speed Drug Absorption in STEMI Patients Undergoing PPCI?

Crushing prasugrel tablets may lead to more favorable drug bioavailability and platelet inhibitory effects compared with consumption of whole tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI), according to a study published March 21 in the Journal of the American College of Cardiology. These findings will be presented at ACC.16 in Chicago.

The study, led by Fabiana Rollini, MD, et al., was a prospective, randomized, open-label, parallel-design study, in which 52 STEMI patients undergoing PPCI were randomly assigned to receive a 60-mg loading dose or prasugrel in either whole tablet or crushed tablet form (both equivalent to six 10-mg tablets). The loading dose of prasugrel was given immediately after the procedure. A maintenance dose of 10 mg of prasugrel was started 24 hours after the loading dose was given. Patients were instructed to continue the maintenance regimen for at least 12 months.

The pharmacokinetics assessments showed that crushed prasugrel was associated with a more than 3-fold faster drug absorption and an almost 2-fold higher maximal plasma concentration of its active metabolite compared with whole tablet administration. P2Y12 reaction unit levels were considerably lower with crushed tablets compared to whole tablets during the 24-hour study time course. 

The faster drug absorption and more rapid and potent antiplatelet effects of crushed prasugrel as shown in this study “may have potential prognostic implications given the known association among peri-PCI platelet reactivity, thrombotic events, and long-term outcomes,” note the authors. They further emphasize that the clinical effects of the study results warrant a larger-scale efficacy trial.

In a related editorial comment, Gennaro Sardella, MD, FACC; Simone Calcagno, MD; and Massimo Mancone, MD, PhD, explain that the study excludes patients in cardiogenic shock requiring a nasogastric tube. “In daily practice, this subset of patients could have a greater benefit from the crushed drug, but … we do not yet know what may interfere with a correct pharmacokinetic/pharmacodynamics assessment,” they add.

Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Acute Heart Failure

Keywords: Biological Availability, Biological Processes, Blood Platelets, Clinical Protocols, Percutaneous Coronary Intervention, Prospective Studies, Shock, Cardiogenic, Tablets, Thrombosis, ACC Annual Scientific Session

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