Platelet Reactivity After Receiving Clopidogrel Compared With Ticagrelor in Patients With Kidney Failure Treated With Hemodialysis: A Randomized Crossover Study

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. Study Design Single-center, prospective, randomized, crossover study. Setting & Participants 25 HD patients in Seoul, Korea. Intervention Patients were randomly assigned to receive clopidogrel (300 mg loading, 75 mg once daily for maintenance dose) or ticagrelor (180 mg loading, 90 mg 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 (100 mg/d). Outcomes & Measurements 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. Limitations 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.