Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China.
Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, P. R. China.
Br J Clin Pharmacol. 2022 Nov;88(11):4870-4880. doi: 10.1111/bcp.15422. Epub 2022 Jun 19.
The risk of ticagrelor-related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events.
Patients diagnosed with acute coronary syndrome and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified.
A total of 631 patients were included and 133 patients had bleeding academic research consortium type 1 or 2 bleeding event. The median ticagrelor concentration (interquartile range) was significantly higher in patients with bleeding events than that in patients without bleeding events (322.6 ng/mL [196.2-458.0 ng/mL] vs. 222.1 ng/mL [140.4-341.9 ng/mL], P < .001). According to the receiver operating characteristic curve, the cut-off value for ticagrelor levels predicting bleeding events was 363.3 ng/mL (area under the curve = 0.65; P < .001, 95% Cl: 0.595-0.700). Pharmacogenomics results showed that P2Y12 (rs6787801, P = .024) and P2Y12 (rs6785930, P = .048) were statistically associated with ticagrelor levels and bleeding events, respectively.
Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with acute coronary syndrome.
替格瑞洛相关出血事件的风险仍然是一个主要的临床关注点，特别是在东亚人群中。先前的研究报告称，亚洲患者的替格瑞洛暴露量高于白种人。这促使我们研究替格瑞洛浓度与出血事件之间的相关性。
纳入被诊断为急性冠状动脉综合征并接受双联抗血小板治疗（阿司匹林和替格瑞洛）的患者，并进行了 12 个月的随访。检测替格瑞洛和主要活性代谢物的谷浓度，并确定了 10 个与替格瑞洛药代动力学和安全性相关的单核苷酸多态性。
共纳入 631 例患者，其中 133 例患者发生了 1 型或 2 型出血学术研究联合会（bleeding academic research consortium，BARC）出血事件。出血事件患者的替格瑞洛浓度中位数（四分位间距）明显高于无出血事件患者（322.6ng/ml[196.2-458.0ng/ml]比 222.1ng/ml[140.4-341.9ng/ml]，P<0.001）。根据受试者工作特征曲线，预测出血事件的替格瑞洛水平截断值为 363.3ng/ml（曲线下面积为 0.65；P<0.001，95%CI：0.595-0.700）。药物基因组学结果显示，P2Y12（rs6787801，P=0.024）和 P2Y12（rs6785930，P=0.048）分别与替格瑞洛水平和出血事件相关。
在中国急性冠状动脉综合征患者中，替格瑞洛血浆浓度与出血事件相关。
