Center for Pharmacogenomics and Precision Medicine and Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.
Nat Rev Cardiol. 2021 Sep;18(9):649-665. doi: 10.1038/s41569-021-00549-w. Epub 2021 May 5.
Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is CYP2C19 genotyping to predict clopidogrel response and assist in selecting antiplatelet therapy after percutaneous coronary intervention. Additional examples include genotyping to guide warfarin dosing and statin prescribing. Increasing evidence exists on outcomes with genotype-guided cardiovascular therapies from multiple randomized controlled trials and observational studies. Pharmacogenetic evidence is accumulating for additional cardiovascular medications. However, data for many of these medications are not yet sufficient to support the use of genotyping for drug prescribing. Ultimately, pharmacogenetics might provide a means to individualize drug regimens for complex diseases such as heart failure, in which the treatment armamentarium includes a growing list of medications shown to reduce morbidity and mortality. However, sophisticated analytical approaches are likely to be necessary to dissect the genetic underpinnings of responses to drug combinations. In this Review, we examine the evidence supporting pharmacogenetic testing in cardiovascular medicine, including that available from several clinical trials. In addition, we describe guidelines that support the use of cardiovascular pharmacogenetics, provide examples of clinical implementation of genotype-guided cardiovascular therapies and discuss opportunities for future growth of the field.
在过去的十年中，遗传药理学检测已在临床实践中出现，以指导选择心血管治疗方法。最常见的应用是 CYP2C19 基因分型，以预测氯吡格雷反应并协助经皮冠状动脉介入治疗后选择抗血小板治疗。其他例子包括指导华法林剂量和他汀类药物处方的基因分型。越来越多的证据表明，来自多个随机对照试验和观察性研究的基因指导心血管治疗的结果。遗传药理学证据也在不断积累，涉及其他心血管药物。然而，许多这些药物的数据还不足以支持使用基因分型来进行药物处方。最终，遗传药理学可能为心力衰竭等复杂疾病的个体化药物治疗方案提供一种方法，其中治疗方法包括越来越多的药物，这些药物已被证明可降低发病率和死亡率。然而，可能需要复杂的分析方法来剖析药物组合反应的遗传基础。在这篇综述中，我们研究了支持心血管医学遗传药理学检测的证据，包括来自几项临床试验的证据。此外，我们描述了支持心血管遗传药理学应用的指南，提供了基因指导心血管治疗的临床实施示例，并讨论了该领域未来发展的机会。
