The authors' affiliations are listed in the Appendix.
N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.
The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.
We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.
At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.
Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).
基因指导（基于药物遗传学）华法林剂量的临床实用性仅在小型临床试验或观察性研究中进行了测试，结果存在争议。
我们将 1015 名患者随机分配到接受治疗的前 5 天的华法林剂量，这些剂量是根据包括临床变量和基因型数据的剂量算法确定的，或者是根据仅包括临床变量的剂量算法确定的。在治疗的前 4 周，所有患者和临床医生都不知道华法林的剂量。主要结局是治疗第 4 或第 5 天至第 28 天期间国际标准化比值（INR）处于治疗范围内的时间百分比。
在 4 周时，基因型指导组的 INR 治疗范围内的时间百分比平均值为 45.2%，临床指导组为 45.4%（调整平均差异[基因型指导组减去临床指导组]，-0.2；95%置信区间，-3.4 至 3.1；P=0.91）。在两种算法之间预测剂量差异为 1 毫克或更多的患者中，两组之间也没有显著的组间差异。然而，剂量策略和种族之间存在显著的相互作用（P=0.003）。在黑人患者中，基因型指导组的 INR 治疗范围内的时间百分比明显低于临床指导组。根据剂量策略，任何 INR 为 4 或更高、大出血或血栓栓塞的联合结局发生率没有显著差异。
基因指导的华法林剂量不能改善治疗的前 4 周的抗凝控制。（由美国国立心脏、肺和血液研究所等资助；COAG ClinicalTrials.gov 编号，NCT00839657）。
