Mugosa Snezana, Radosavljevic Ivan, Sahman Majda, Djordjevic Natasa, Todorovic Zoran
Department of Pharmacology, Faculty of Medicine, University of Montenegro, 81000 Podgorica, Montenegro.
Clinical Trials Department, Institute for Medicines and Medical Devices of Montenegro, 81000 Podgorica, Montenegro.
Open Med (Wars). 2022 Apr 7;17(1):694-701. doi: 10.1515/med-2021-0371. eCollection 2022.
This study aimed to investigate the possible influence of genetic and non-genetic factors on the incidence of clopidogrel adverse drug reactions (ADRs) in cardiology patients, including the most important alleles, namely *2 and *17, as well as compliance, dose, drug interactions, and clinical factors. A total of 102 clopidogrel-treated adult Caucasian patients hospitalized at the Cardiology Department of the Clinical Center of Montenegro were enrolled in the study. Data on clinical outcomes of interest were obtained by intensive monitoring ADRs during hospitalization and one year after hospital discharge. Genotyping for *2 and *17 was conducted using the real-time polymerase chain reaction method. ADRs were characterized using the Rawlins and Thompson classification and the World Health Organization criteria. Causality was assessed using the Naranjo probability scale. ADRs to clopidogrel were observed in 9 of 102 patients (8.8%). The observed frequencies of *2 and *17 were 13.2 and 25.5%, respectively. Our study, which is the first to report the frequency of polymorphism in the Montenegrin population, as well as to link the pharmacovigilance of clopidogrel with gene variability, shows that the incidence of ADRs of clopidogrel in cardiac patients is high and depends on polymorphisms, comedication/drug interactions, and gastrointestinal comorbidity.
本研究旨在调查遗传和非遗传因素对心脏病患者氯吡格雷药物不良反应（ADR）发生率的可能影响，包括最重要的等位基因，即2和17，以及依从性、剂量、药物相互作用和临床因素。共有102名在黑山临床中心心脏病科住院的接受氯吡格雷治疗的成年白种人患者参与了本研究。通过在住院期间和出院后一年对ADR进行强化监测，获得了感兴趣的临床结局数据。使用实时聚合酶链反应方法对2和17进行基因分型。使用罗林斯和汤普森分类法以及世界卫生组织标准对ADR进行特征描述。使用纳兰霍概率量表评估因果关系。102名患者中有9名（8.8%）出现了氯吡格雷的ADR。观察到的2和17的频率分别为13.2%和25.5%。我们的研究首次报告了黑山人群中多态性的频率，并将氯吡格雷的药物警戒与基因变异性联系起来，结果表明心脏病患者中氯吡格雷ADR的发生率很高，且取决于多态性、合并用药/药物相互作用和胃肠道合并症。
