A pharmacogenetic versus a clinical algorithm for warfarin dosing.
A pharmacogenetic versus a clinical algorithm for warfarin dosing.
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DOI：
10.1056/nejmoa1310669
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发表时间：
2013-12-12
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影响因子：
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通讯作者：
COAG Investigators
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作者：
Kimmel SE;French B;Kasner SE;Johnson JA;Anderson JL;Gage BF;Rosenberg YD;Eby CS;Madigan RA;McBane RB;Abdel-Rahman SZ;Stevens SM;Yale S;Mohler ER 3rd;Fang MC;Shah V;Horenstein RB;Limdi NA;Muldowney JA 3rd;Gujral J;Delafontaine P;Desnick RJ;Ortel TL;Billett HH;Pendleton RC;Geller NL;Halperin JL;Goldhaber SZ;Caldwell MD;Califf RM;Ellenberg JH;COAG Investigators
基因型指导（基于药物遗传学）华法林给药的临床效用仅在小型临床试验或观察性研究中进行了测试，结果不明确。我们随机分配1015例患者在治疗的前5天接受华法林剂量，根据包括临床变量和基因型数据的剂量算法或仅包括临床变量的剂量算法确定。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。主要结局是从治疗第4天或第5天至第28天国际标准化比值（INR）在治疗范围内的时间百分比。第4周时，基因型指导组和临床指导组治疗范围内的平均时间百分比分别为45.2%和45.4%（校正平均差异，[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）。两种算法之间的预测剂量差异为1 mg/天或更高的患者之间也没有显著的组间差异。然而，给药策略和人种之间存在显著的相互作用（P = 0.003）。在黑人患者中，基因型指导组治疗范围内的平均时间百分比低于临床指导组。根据给药策略，任何INR ≥ 4、大出血或血栓栓塞的联合结局发生率无显著差异。在治疗的前4周内，基因型指导的华法林剂量并没有改善抗凝控制。（由国家心肺血液研究所和其他机构资助; COAG www.example.com编号，NCT 00839657。
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.)