Abstract

OBJECTIVES
The purpose of this study is to assess the pharmacodynamic effects of different prasugrel dosing regimens in patients on maintenance prasugrel therapy.
BACKGROUND
There are a growing number of patients on chronic prasugrel therapy regimens, leading to questions about the dosing regimen of prasugrel to administer if percutaneous coronary intervention is required.
METHODS
This is a prospective pharmacodynamic study in patients (n = 64) receiving maintenance prasugrel therapy who were randomly allocated to a 10 mg, 30 mg, or 60 mg dose of prasugrel. Pharmacodynamic assessments using multiple assays were conducted at 3 timepoints (baseline and 1 h and 4 h after dosing).
RESULTS
Intragroup comparisons showed that a 60 mg dose reduced the platelet reactivity index (PRI) after 1 h (p = 0.004) and 4 h (p < 0.001, primary endpoint; p = 0.002 between 1 h and 4 h). A 30 mg dose also reduced PRI levels at 1 h (p = 0.006) and 4 h (p < 0.001; p = 0.044 between 1 h and 4 h). A 10 mg dose was associated with modest pharmacodynamic effects. Intragroup comparisons showed similar findings with VerifyNow-P2Y12 and light transmission aggregometry. Intergroup comparisons showed that a 60 mg dose achieved lower PRI levels than 30 mg at 4 h (p = 0.05), and a numerical trend toward better pharmacodynamic effects at 1 h (p = 0.171). Intergroup comparisons were similar with VerifyNow-P2Y12, but not light transmission aggregometry.
CONCLUSIONS
For patients on maintenance prasugrel therapy, a 60 mg dosing strategy is associated with faster and higher platelet inhibition compared with lower doses, as assessed by P2Y(12) specific assays. (Impact of Prasugrel Re-load on Platelet Aggregation in Patients on Chronic Prasugrel Therapy; NCT01201772).

Links

Publisher Full Text

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Authors

Tello-Montoliu A, Tomasello SD, Ferreiro JL, Ueno M, Seecheran N, Desai B, Kodali M, Charlton RK, Box LC, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ

Institution

University of Florida College of Medicine, Jacksonville, Jacksonville, Florida 32209, USA.

Source

Journal of the American College of Cardiology 59:19 2012 May 8 pg 1681-7

MeSH

Adult
Aged
Dose-Response Relationship, Drug
Drug Administration Schedule
Ethnic Groups
Female
Fibrinolytic Agents
Humans
Male
Middle Aged
Piperazines
Platelet Aggregation
Prospective Studies
Purinergic P2Y Receptor Antagonists
Receptors, Purinergic P2Y12
Thiophenes
Time Factors

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22554598