Beitelshees Amber L, Voora Deepak, Lewis Joshua P
Program for Personalized and Genomic Medicine and Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
Center for Applied Genomics & Precision Medicine, Department of Medicine, Duke School of Medicine, Durham, NC, USA.
Pharmgenomics Pers Med. 2015 Feb 9;8:43-61. doi: 10.2147/PGPM.S52900. eCollection 2015.
In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin) and anticoagulation (ie, warfarin) medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran) agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and anticoagulation therapy. However, several factors may limit its usefulness and should be considered.
近年来,人们付出了巨大努力来更好地理解遗传因素对众多药物疗效和安全性的影响。这些研究表明,利用药物遗传学数据为医生的决策提供依据,在减少治疗期间的临床事件、药物不良反应和医疗相关费用方面,具有极大潜力来改善患者护理。事实上,鉴于越来越多的证据表明基因变异与药物反应的差异有关,将此类信息整合到临床环境中可能特别适用于抗血小板和抗凝治疗。在本综述中,我们总结了目前最常用的抗血小板药物(即氯吡格雷和阿司匹林)和抗凝药物(即华法林)的药物遗传学信息。此外,我们强调了基因变异性在对新一代抗血小板药物(普拉格雷和替格瑞洛)和抗凝药物(达比加群)反应中的已知作用。虽然有力的证据表明基因变异是抗血小板和抗凝治疗反应的重要决定因素,但药物遗传学检测在临床应用中仍存在重大障碍,本文对此进行了描述。此外,我们简要讨论了新诊断靶点和治疗策略的发展以及对改善患者护理的意义。总之,药物遗传学检测可以提供重要信息,帮助临床医生开出最个性化、最有效的抗血小板和抗凝治疗方案。然而,有几个因素可能会限制其效用,应予以考虑。