title: Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity.
abstract: BACKGROUND
  High on-treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel.
  
  
  OBJECTIVE
  The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR.
  
  
  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.
authors: Department of Cardiology, Patras University Hospital, Patras, Greece. dalex@med.upatras.gr
authors: D
authors: D
authors: Alexopoulos
authors: A
authors: A
authors: Panagiotou
authors: I
authors: I
authors: Xanthopoulou
authors: D
authors: D
authors: Komninakis
authors: G
authors: G
authors: Kassimis
authors: P
authors: P
authors: Davlouros
authors: C
authors: C
authors: Fourtounas
authors: D
authors: D
authors: Goumenos
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D006435:Renal Dialysis; D016037:Single-Blind Method; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine