Study Supports Using Crushed Prasugrel Tablets in Patients With STEMI Undergoing PPCI

April 26, 2016—CRUSH study investigators have concluded that crushed prasugrel tablets lead to faster drug absorption, and consequently, more prompt and potent antiplatelet effects compared with whole tablet ingestion in patients wtih ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Fabiana Rollini, MD, et al published the study results in the Journal of the American College of Cardiology (JACC, 2016;67:1994–2004).

The study’s background is that platelet inhibitory effects induced by oral P2Y12 receptor antagonists are delayed in patients with STEMI undergoing PPCI, which may be attributed to impaired absorption affecting drug pharmacokinetics (PK) and pharmacodynamics (PD). The CRUSH study sought to determine whether crushing prasugrel is associated with more favorable drug bioavailability and platelet inhibitory effects compared with whole tablets in these patients. 

As summarized in JACC, this prospective, randomized, open-label study assessed STEMI patients undergoing PPCI (n = 52) who were treated with a prasugrel 60-mg loading dose (LD) either as whole or crushed tablets. PK/PD analyses were performed at seven time points. PD effects were measured as P2Y12 reaction units and platelet reactivity index and PK by plasma levels of prasugrel’s active metabolite.

The investigators found that compared with whole tablets, crushed prasugrel led to reduced P2Y12 reaction units by 30 minutes post-LD, which persisted at 1, 2 (164 vs 95; primary endpoint), and 4 hours post-LD. Significant differences were no longer present at 6 hours post-LD. Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with crushed prasugrel. PK analyses showed a > threefold faster absorption with crushed compared with whole prasugrel, reported the investigators in JACC.