Pharmacodynamic effects of prasugrel dosing regimens in patients on maintenance prasugrel therapy: results of a prospective randomized study.

Abstract

The purpose of this study is to assess the pharmacodynamic effects of different prasugrel dosing regimens in patients on maintenance prasugrel therapy. 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. 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). 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. 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).