基因型指导下的阿哌沙班和依度沙班剂量调整的随机试验。
A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.
机构信息
The authors' affiliations are listed in the Appendix.
出版信息
N Engl J Med. 2013 Dec 12;369(24):2304-12. doi: 10.1056/NEJMoa1311388. Epub 2013 Nov 19.
BACKGROUND
Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy.
METHODS
We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks.
RESULTS
A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events.
CONCLUSIONS
Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).
背景
观察性证据表明，使用基因型指导的剂量算法可能会提高 acenocoumarol 和 phenprocoumon 治疗的有效性和安全性。
方法
我们进行了两项单盲、随机试验，比较了一种基因型指导的剂量算法，该算法包括临床变量和 CYP2C9 和 VKORC1 的基因分型，以及一种仅包括临床变量的剂量算法，用于启动房颤或静脉血栓栓塞患者的 acenocoumarol 或 phenprocoumon 治疗。主要结局是治疗开始后 12 周内国际标准化比值（INR；目标范围 2.0 至 3.0）的时间百分比。由于招募人数较少，两项试验合并进行分析。主要结局评估了至少随访 10 周的患者。
结果
共纳入 548 例患者（基因型指导组 273 例，对照组 275 例）。至少随访 10 周的基因型指导组患者有 239 例，对照组有 245 例。接受基因型指导剂量的患者的 INR 治疗范围内的时间百分比为 61.6%，接受临床指导剂量的患者为 60.2%（P=0.52）。两组间几个次要结局无显著差异。两组治疗开始后第 4 周时的治疗范围内时间百分比分别为 52.8%和 47.5%（P=0.02）。两组出血或血栓栓塞事件的发生率无显著差异。
结论
在治疗开始后的 12 周内，acenocoumarol 或 phenprocoumon 的基因型指导剂量并未改善 INR 治疗范围内的时间百分比。（由欧盟第七框架计划和其他机构资助；EU-PACT ClinicalTrials.gov 编号，NCT01119261 和 NCT01119274）。
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