A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II)
A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II)
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DOI：
10.1161/circulationaha.111.070920
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发表时间：
2012-04-24
期刊：
影响因子：
37.8
通讯作者：
Carlquist, John F.
中科院分区：
文献类型：
--
作者：
Anderson, Jeffrey L.;Horne, Benjamin D.;Carlquist, John F.
背景-Warcraft的特点是个体剂量需求的显著变化和狭窄的治疗窗口。药物遗传学（PG）可以提高给药效率和安全性，但临床试验证据不足。方法和结果-一项比较两种药物遗传学算法和标准护理的个体化Warranty给药的随机和临床有效性试验（CoumaGen-II）包括2项比较：（1）改良1步（PG-1）与3步算法（PG-2）的盲法随机比较（N=504），以及（2）在平行对照组（N=1866）中，PG指导与使用标准剂量的任一算法的临床有效性比较。一种快速方法提供了同一天的CYP 2C 9和VKORC 1基因分型。主要结局为1个月和3个月时超出范围的国际标准化比值百分比以及治疗范围内的时间百分比。主要分析为改良意向治疗。在随机比较中，PG-2在1个月和3个月时超出范围的国际标准化比值百分比以及3个月时处于治疗范围内的时间百分比方面非劣效于PG-1，但非上级。然而，合并的PG队列上级平行对照组（1个月时超出范围的国际标准化比值百分比分别为31%和42%; 3个月时分别为30%和42%;治疗范围内的时间百分比分别为69%和58%，71%和59%，所有P= 4，
Background-Warfarin is characterized by marked variations in individual dose requirements and a narrow therapeutic window. Pharmacogenetics (PG) could improve dosing efficiency and safety, but clinical trials evidence is meager.Methods and Results-A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) comprised 2 comparisons: (1) a blinded, randomized comparison of a modified 1-step (PG-1) with a 3-step algorithm (PG-2) (N=504), and (2) a clinical effectiveness comparison of PG guidance with use of either algorithm with standard dosing in a parallel control group (N=1866). A rapid method provided same-day CYP2C9 and VKORC1 genotyping. Primary outcomes were percentage of out-of-range international normalized ratios at 1 and 3 months and percentage of time in therapeutic range. Primary analysis was modified intention to treat. In the randomized comparison, PG-2 was noninferior but not superior to PG-1 for percentage of out-of-range international normalized ratios at 1 month and 3 months and for percentage of time in therapeutic range at 3 months. However, the combined PG cohort was superior to the parallel controls (percentage of out-of-range international normalized ratios 31% versus 42% at 1 month; 30% versus 42% at 3 months; percentage of time in therapeutic range 69% versus 58%, 71% versus 59%, respectively, all P= 4 and