Antiplatelet effects of prasugrel vs. double clopidogrel in patients on
hemodialysis and with high on-treatment platelet reactivity.
Author(s): Alexopoulos D, Panagiotou A, Xanthopoulou I, Komninakis D, Kassimis G, Davlouros
P, Fourtounas C, Goumenos D.
Affiliation(s): Department of Cardiology, Patras University Hospital, Patras, Greece.
dalex@med.upatras.gr
Publication date & source: 2011, J Thromb Haemost. , 9(12):2379-85
BACKGROUND: High on-treatment platelet reactivity (HTPR) is frequent in patients
on hemodialysis (HD) receiving clopidrogel.
OBJECTIVES: The primary aim of this study was to determine the antiplatelet
effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR.
PATIENTS/METHODS: We performed a prospective, single-center, single-blind,
investigator-initiated, randomized, crossover study to compare platelet
inhibition by prasugrel 10 mg day(-1) with that by high-dose 150 mg day(-1)
clopidogrel in 21 patients on chronic HD with HTPR. Platelet function was
assessed with the VerifyNow assay, and genotyping was performed for CYP2C19*2
carriage.
RESULTS: The primary endpoint of platelet reactivity (PR, measured in P2Y12
reaction units [PRU]) was lower in patients receiving prasugrel (least squares
[LS] estimate 156.6, 95% confidence interval [CI] 132.2-181.1) than in those
receiving high-dose clopidogrel (LS 279.9, 95% CI 255.4-304.3), P < 0.001). The
LS mean differences between the two treatments were - 113.4 PRU (95% CI - 152.9
to - 73.8, P < 0.001) and - 163.8 PRU (95% CI - 218.1 to - 109.2, P < 0.001) in
non-carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR
rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%,
P < 0.001) and in non-carriers (25.7% vs. 80%, P = 0.003). All carriers continued
to show HTPR while receiving high-dose clopidogrel, but none showed it while
receiving prasugrel.
CONCLUSIONS: In HD patients exhibiting HTPR following standard clopidogrel
treatment, prasugrel 10 mg day(-1) is significantly more efficient than doubling
the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect
seems to be influenced by carriage of the loss-of-function CYP2C19*2 allele.
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