Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity

. 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] 132.2181.1) than in those receiving high-dose clopidogrel (LS 279.9, 95% CI 255.4304.3), 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 day1 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.