Porlán Manuel Veas, Tello-Montoliu Antonio, López-García Cecilia, Gil-Pérez Pablo, Quintana-Giner Miriam, López-Gálvez Raquel, Rivera-Caravaca José Miguel, Marín Francisco, Figal Domingo Pascual
Cardiology Department, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, IMIB-Arrixaca, CIBERCV, Murcia, Spain.
Int J Cardiol Heart Vasc. 2023 Mar 27;46:101195. doi: 10.1016/j.ijcha.2023.101195. eCollection 2023 Jun.
Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS.
Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR < 60 mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose.
48 patients were recruited (eGFR ≥ 60 mL/min: 35 and eGFR < 60 mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7 days of treatment (p = 0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p = 0.02 and 0.04 respectively) and 6 h of loading (p = 0.042 and 0.08 respectively).
No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4 h of the loading dose.
慢性肾衰竭（CKD）与血小板反应性增加及氯吡格雷临床获益降低相关。与氯吡格雷相比，替格瑞洛具有更有利的药效学和药代动力学特征，这已转化为急性冠状动脉综合征（ACS）患者更好的临床结局。我们进行了一项前瞻性机制队列研究，以调查肾衰竭对急性ACS患者替格瑞洛药代动力学和药效学的影响。
根据估计的肾清除率将患者分为两组（估算肾小球滤过率[eGFR]≥60 mL/分钟和eGFR<60 mL/分钟）。在基线、替格瑞洛负荷剂量后及出院时使用VerifyNow系统测定血小板功能。此外，在负荷剂量后第1小时测定替格瑞洛及其活性代谢物（AR-C124910XX）的水平。
招募了48例患者（eGFR≥60 mL/分钟：35例，eGFR<60 mL/分钟：13例）。在负荷剂量后或治疗7天后，两组在血小板抑制方面无显著差异（p = 0.219）。然而，肾功能正常的受试者中替格瑞洛及其活性代谢物的水平低于CKD患者，尤其是在负荷后4小时（分别为p = 0.02和0.04）和6小时（分别为p = 0.042和0.08）。
不同肾功能的患者使用替格瑞洛治疗后在血小板抑制方面未观察到差异，尽管肾功能损害患者在负荷剂量4小时后替格瑞洛和AR-C124910XX水平较高。
