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CRUSH: Crushed prasugrel absorbed faster in patients with STEMI undergoing PCI
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CHICAGO — In patients with STEMI requiring PCI, crushed prasugrel tablets are absorbed faster than whole tablets, leading to stronger and quicker antiplatelet effects.
When patients with STEMI who need PCI are administered an oral P2Y12 receptor antagonist such as prasugrel (Effient, Daiichi Sankyo/Eli Lilly), platelet inhibition may be delayed, possibly because of impaired absorption.
Dominick J. Angiolillo, MD, PhD, and colleagues investigated whether crushing prasugrel tablets before administration would improve the drug’s pharmacokinetics and pharmacodynamics and lead to better absorption, and possibly improved platelet inhibition.
Dominick J. Angiolillo
The researchers conducted a randomized, prospective, open-label study of 52 patients with STEMI undergoing primary PCI needing a 60-mg loading dose of prasugrel. Patients were assigned whole or crushed prasugrel tablets.
Angiolillo, from the division of cardiology at University of Florida College of Medicine–Jacksonville and Cardiology Today’s Intervention Editorial Board member, and colleagues performed pharmacokinetics and pharmacodynamics analyses at seven time points. They measured pharmacokinetics by plasma levels of the active metabolite of prasugrel and pharmacodynamics as P2Y12 reaction units and platelet reactivity index.
The data were presented at the American College of Cardiology Scientific Session.
At 30 minutes, 1 hour, 2 hours and 4 hours after dosing, crushed prasugrel was associated with reduced P2Y12 reaction units compared with whole tablets (164 vs. 95 at 2 hours; least square mean difference = 68; 95% CI, 10-126). The researchers noted that there was no longer a difference at 6 hours. There was a similar difference in platelet reactivity index over time, according to the findings.
High on-treatment platelet reactivity rates were lower with crushed prasugrel compared with whole tablets (P at 30 minutes = .03; P at 1 hour = .001; P at 2 hours = .044).
When the researchers performed pharmacokinetic analyses, they found that absorption was more than threefold faster with crushed prasugrel than with whole tablets, with higher concentrations of plasma levels of the active metabolite at 30 minutes and 1 hour in patients assigned the crushed tablets.
“In STEMI patients undergoing [primary PCI], crushed prasugrel administration is associated with faster drug absorption and more prompt and potent antiplatelet effects compared with whole tablet ingestion,” Angiolillo and colleagues wrote in the Journal of the American College of Cardiology. “Our findings may have potential prognostic implications given the known association among peri-PCI platelet reactivity, thrombotic events and long-term outcomes.” – by Erik Swain
References:
Rollini F, et al. Abstract 1125M-01. Presented at: American College of Cardiology Scientific Session; April 2-4, 2016; Chicago.
Rollini F, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.02.045.
Disclosure: The study was funded by an investigator-initiated grant from Daiichi Sankyo and Eli Lilly. Angiolillo reports financial ties with Daiichi Sankyo, Eli Lilly and numerous other pharmaceutical and medical device companies. The other researchers report no relevant financial disclosures.