Prasugrel Reload Dosing Regimen Reduces High On-Treatment Platelet Reactivity Rates

SAN FRANCISCO, CA—Patients with acute coronary syndrome on maintenance dose prasugrel had a reduction in high on-treatment platelet reactivity rates after a prasugrel reload strategy, according to a post hoc analysis of a prospective, randomized, open-label pharmacodynamic study presented at ACC.13, the American College of Cardiology’s 62nd Annual Scientific Session.

Noting that “prior investigations have observed that up to 25% of patients treated with prasugrel exhibit high on-treatment platelet reactivity,” Jose Luis Ferreiro, MD, of the University of Florida College of Medicine-Jacksonville, Jacksonville, FL, and the Heart Diseases Institute, Hospital Universitari de Bellvitge-IDIBELL, University of Barcelona, Barcelona, Spain, and colleagues assessed high on-treatment platelet reactivity rates, including how different reloading dose regimens and type of assay may affect these rates.

In the study, 64 patients on prasugrel 10mg/day maintenance dose therapy for at least 14 days were randomized to receive a 10mg (n=22), 30mg (n=21), or 60mg (n=21) loading dose of prasugrel. Pharmacodynamic assessments were conducted at three time points: baseline (trough), one, and four hours after the loading dose.

Established cut-off points used to define high on-treatment platelet reactivity were based on pharmacodynamic measures using the VerifyNow-P2Y12 assay (P2Y12 reaction units >230), the vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index ≥50%), and light transmission aggregometry (LTA) using 5 and 20mmol/L as stimuli (>46% and >59% maximal platelet aggregation), which have been associated with adverse ischemic events.

“At baseline, the overall percentage of patients with high on-treatment platelet reactivity varied between 6.3% and 12.5%,” Dr. Ferreiro noted.”

The 60mg loading dose regimen significantly reduced PRI at one hour (P=0.002) and four hours (P<0.001) versus the 10mg dose at both time points and vs. the 30mg dose at four hours (P<0.05), the investigators found. Compared with the 10mg dose, the 30mg loading dose resulted in a numerically higher platelet inhibition at one hour, becoming significant at four hours (P<0.001). Similar results were obtained with VN-P2Y12 and LTA.