Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea.
Am J Kidney Dis. 2015 Jun;65(6):916-24. doi: 10.1053/j.ajkd.2014.11.023. Epub 2015 Jan 24.
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.
Single-center, prospective, randomized, crossover study.
SETTING & PARTICIPANTS: 25 HD patients in Seoul, Korea.
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).
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.
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.
Single-center study with a small number of patients, not a double-blind study, and not intention-to-treat analysis.
Ticagrelor may result in more rapid and greater platelet inhibition than clopidogrel in patients with kidney failure receiving HD.
接受维持性血液透析（HD）治疗的肾衰竭患者对氯吡格雷反应不佳。因此，HD 患者需要更有效的血小板抑制策略。
单中心、前瞻性、随机、交叉研究。
韩国首尔的 25 名 HD 患者。
患者随机接受氯吡格雷（负荷剂量 300mg，维持剂量 75mg 每日 1 次）或替格瑞洛（负荷剂量 180mg，维持剂量 90mg 每日 2 次）治疗 14 天，洗脱期 14 天后进行交叉治疗，再治疗 14 天。所有患者均服用阿司匹林（100mg/d）。
在首次负荷剂量前和负荷剂量后 1、5、48 小时以及 14 天，评估血小板功能。在洗脱期，通过光透射聚集测定法和 VerifyNow P2Y12 测定法在最后一次给药后 1 小时和 2、4 和 14 天评估血小板功能，并对 CYP2C19*2 等位基因进行基因分型。评估最大聚集程度、血小板聚集抑制（IPA）、P2Y12 反应单位（PRUs）和抑制百分比。我们进行了符合方案分析，排除了未完成方案的患者。
9 名患者未完成方案（7 名因不良事件；2 名，不依从）。与氯吡格雷相比，负荷后 1、5、48 小时和 14 天，替格瑞洛的 IPA 更高。负荷后 5 小时，替格瑞洛组比氯吡格雷组达到 IPA>50%（分别为 75%和 12%；P<0.05）和 IPA>70%（分别为 44%和 0%；P<0.05）的患者比例更高。接受替格瑞洛治疗的患者血小板抑制作用的起始和消退速度快于接受氯吡格雷治疗的患者（P<0.05）。无论 CYP2C19*2 等位基因如何，替格瑞洛组的 PRUs 始终显著低于氯吡格雷组。
单中心研究，患者数量少，非双盲研究，非意向治疗分析。
在接受 HD 治疗的肾衰竭患者中，替格瑞洛可能比氯吡格雷更快、更有效地抑制血小板。
