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)
Key Words
crushed tablet
pharmacodynamic
pharmacokinetic
platelets
Abbreviations and Acronyms
HPR
high on-treatment platelet reactivity
PD
pharmacodynamic
PK
pharmacokinetic
PPCI
primary percutaneous coronary intervention
PRI
platelet reactivity index
PRU
P2Y12 reaction units
STEMI
ST-segment elevation myocardial infarction
VASP
whole blood vasodilator-stimulated phosphoprotein
VN-P2Y12
VerifyNow P2Y12 assay
Cited by (0)
The present study was funded by an investigator-initiated grant from Daiichi-Sankyo and Eli Lilly and Company. Daiichi-Sankyo and Eli Lilly and Company had no role in study design conception, conduct of the study, or the decision on where to publish these results. Dr. Angiolillo has received payment as an individual for consulting fee or honoraria from Sanofi, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular, and PLx Pharma; has participated in review activities from CeloNova, Johnson & Johnson, and St. Jude Medical; and has received institutional payments for grants from GlaxoSmithKline, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Janssen Pharmaceuticals, Inc., Osprey Medical, Inc., Novartis, CSL Behring, and Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
