Crushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Intervention: The CRUSH Study

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• 作者：Fabiana Rollini ; MD ; Francesco Franchi ; MD ; Jenny Hu ; MD ; Megha Kureti ; MD ; Niti Aggarwal ; MD ; Ashwin Durairaj ; MD ; Yongwhi Park ; MD ; Michael Seawell ; MD ; Pedro Cox-Alomar ; MD ; Martin M. Zenni ; MD ; Luis A. Guzman ; MD ; Siva Suryadevara ; MD ; Patrick Antoun ; MD ; Theodore A. Bass ; MD ; Dominick J. Angiolillo ; MD ; PhD ; ^{dominick.angiolillo@jax.ufl.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：crushed tablet ; pharmacodynamic ; pharmacokinetic ; platelets
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：3 May 2016
• 年：2016
• 卷：67
• 期：17
• 页码：1994-2004
• 全文大小：1009 K

文摘

Platelet inhibitory effects induced by oral P2Y₁₂ receptor antagonists are delayed in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), which may be attributed to impaired absorption affecting drug pharmacokinetics (PK) and pharmacodynamics (PD). Crushing tablets has been suggested to lead to more favorable PK/PD profiles. To date, no studies have investigated the PK/PD effects of crushing prasugrel.

Objectives

This study sought to determine whether crushing prasugrel is associated with more favorable drug bioavailability and platelet inhibitory effects compared with whole tablets in STEMI patients undergoing PPCI.

Methods

Our 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 7 time points. PD effects were measured as P2Y₁₂ reaction units and platelet reactivity index, and PK by plasma levels of prasugrel’s active metabolite.

Results

Compared with whole tablets, crushed prasugrel led to reduced P2Y₁₂ reaction units by 30 min post-LD, which persisted at 1, 2 (164 vs. 95; least square mean difference = 68; 95% confidence interval: 10 to 126; primary endpoint), and 4 h post-LD. Significant differences were no longer present at 6 h 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 >3-fold faster absorption with crushed compared with whole prasugrel.

Conclusions

In STEMI patients undergoing PPCI, crushed prasugrel leads to faster drug absorption, and consequently, more prompt and potent antiplatelet effects compared with whole tablet ingestion. (Pharmacological Effects of Crushing Prasugrel in STEMI Patients; NCT02212028)