title: Platelet reactivity after receiving clopidogrel compared with ticagrelor in patients with kidney failure treated with hemodialysis: a randomized crossover study.
abstract: BACKGROUND
  Patients with kidney failure treated with maintenance hemodialysis (HD) are poor responders to clopidogrel. More beneficial platelet-inhibiting strategies in HD patients therefore are required.
  
  
  METHODS
  Single-center, prospective, randomized, crossover study.
  
  
  METHODS
  25 HD patients in Seoul, Korea.
  
  
  METHODS
  Patients were randomly assigned to receive clopidogrel (300mg loading, 75mg once daily for maintenance dose) or ticagrelor (180mg loading, 90mg twice daily for maintenance dose) for 14 days, and after a 14-day washout period, crossover treatment for another 14 days. All patients received aspirin (100mg/d).
  
  
  METHODS
  Platelet function was evaluated predosing and at 1, 5, and 48 hours and 14 days after the first loading dose. During the offset phase, platelet function was assessed at 1 hour and 2, 4, and 14 days after the last dose by light transmittance aggregometry and the VerifyNow P2Y12 assay, and patients were genotyped for the CYP2C19*2 allele. Maximal extent of aggregation, inhibition of platelet aggregation (IPA), P2Y12 reaction units (PRUs), and percentage of inhibition were evaluated. We performed per-protocol analysis, excluding patients who did not complete the protocol.
  
  
  RESULTS
  9 patients did not complete the protocol (7 patients due to adverse events; 2, nonadherence). Higher IPA occurred with ticagrelor than with clopidogrel at 1, 5, and 48 hours and 14 days after loading. By 5 hours after loading, a greater proportion of patients in the ticagrelor group than in the clopidogrel group achieved IPA>50% (75% vs 12%, respectively; P<0.05) and IPA>70% (44% vs 0%, respectively; P<0.05). Rates (slope) of onset and offset of the antiplatelet effect were faster in patients receiving ticagrelor than for those receiving clopidogrel (P<0.05). Regardless of CYP2C19*2 allele, the ticagrelor group had significantly lower PRUs at all times than the clopidogrel group.
  
  
  CONCLUSIONS
  Single-center study with a small number of patients, not a double-blind study, and not intention-to-treat analysis.
  
  
  CONCLUSIONS
  Ticagrelor may result in more rapid and greater platelet inhibition than clopidogrel in patients with kidney failure receiving HD.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea. Electronic address: aprilhwan@naver.com.
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Woo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jin Bae
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Woo-Shik
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kwon Sam
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Chun Gyoo
authors.initials: CG
authors.lastname: Ihm
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea. Electronic address: mylovekw@hanmail.net.
authors.forename: Weon
authors.initials: W
authors.lastname: Kim
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D006435:Renal Dialysis; D016037:Single-Blind Method; D013927:Thrombosis / Q000517:prevention & control*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: Platelet inhibition; antiplatelet therapy; clopidogrel; end-stage renal disease (ESRD); hemodialysis (HD); high on-treatment platelet reactivity (HTPR); kidney failure; platelet aggregation assay; platelet reactivity; thrombosis; ticagrelor