Cardiovascular Department, Intermountain Medical Center, Salt Lake City, UT, USA.
Mol Diagn Ther. 2011 Oct 1;15(5):255-64. doi: 10.1007/BF03256417.
Warfarin, the most common oral anticoagulant, is the ideal candidate for pharmacogenetic dosing and gene-based 'individualization' of care. A plethora of studies have shown that stable dose requirements can be predicted using sequence variants in the CYP2C9 and VKORC1 genes in both sexes and in different races. Multiple clinical trials of pharmacogenetic warfarin dosing have been conducted with various methods, including several randomized trials that have been completed. These studies have reported varying degrees of success and some have been met with substantial skepticism. Other much larger randomized trials are ongoing. This paper reviews and synthesizes the various clinical trials that have been published and touches on the potential that the ongoing trials offer. The emergence of new oral anticoagulants also raises the question of the relevance of pharmacogenetic warfarin dosing for the future. The cost of genotype-guided dosing is substantial, and none of the studies to date have shown a cost-benefit of using pharmacogenetic warfarin dosing in clinical practice. Although pharmacogenetics-guided warfarin dosing has been discussed for many years, the currently available data regarding this genetically individualized dosing suggest that pharmacogenetics remains unproven for use in clinical warfarin prescription.
华法林是最常用的口服抗凝剂，是药物遗传学剂量调整和基于基因的“个体化”护理的理想候选药物。大量研究表明，使用 CYP2C9 和 VKORC1 基因中的序列变异，可以预测男女两性和不同种族人群中稳定的剂量需求。已经使用各种方法进行了多次华法林药物遗传学剂量调整的临床试验，包括已经完成的几项随机试验。这些研究报告了不同程度的成功，有些研究受到了很大的质疑。其他更大规模的随机试验仍在进行中。本文综述并综合了已发表的各种临床试验，并探讨了正在进行的试验所带来的可能性。新型口服抗凝剂的出现也提出了华法林药物遗传学剂量调整在未来的相关性问题。基因指导剂量的成本很高，迄今为止，尚无研究表明在临床实践中使用华法林药物遗传学剂量调整具有成本效益。尽管华法林的药物遗传学剂量调整已经讨论了多年，但目前关于这种基因个体化剂量的可用数据表明，药物遗传学在临床华法林处方中的应用仍未得到证实。
