Dahal Khagendra, Sharma Sharan P, Fung Erik, Lee Juyong, Moore Jason H, Unterborn John N, Williams Scott M
Department of Medicine, LRGHealthcare, Laconia, NH.
Department of Medicine, Englewood Hospital and Medical Center, Englewood, NJ.
Chest. 2015 Sep;148(3):701-710. doi: 10.1378/chest.14-2947.
Warfarin is a widely prescribed anticoagulant, and its effect depends on various patient factors including genotypes. Randomized controlled trials (RCTs) comparing genotype-guided dosing (GD) of warfarin with standard dosing have shown mixed efficacy and safety outcomes. We performed a meta-analysis of all published RCTs comparing GD vs standard dosing in adult patients with various indications of warfarin use.
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and relevant references for English language RCTs (inception through March 2014). We performed the meta-analysis using a random effects model.
Ten RCTs with a total of 2,505 patients were included in the meta-analysis. GD compared with standard dosing resulted in a similar % time in therapeutic range (TTR) at ≤ 1 month follow-up (39.7% vs 40.2%; mean difference [MD], -0.52 [95% CI, -3.15 to 2.10]; P = .70) and higher % TTR (59.4% vs 53%; MD, 6.35 [95% CI, 1.76-10.95]; P = .007) at > 1 month follow-up, a trend toward lower risk of major bleeding (risk ratio, 0.46 [95% CI, 0.19-0.1.11]; P = .08) at ≤ 1 month follow-up and lower risks of major bleeding (0.34 [95% CI, 0.16-0.74], P = .006) at > 1-month follow-up, and shorter time to maintenance dose (TMD) (24.6 days vs 34.1 days; MD, -9.54 days [95% CI, -18.10 to -0.98]; P = .03) at follow-up but had no effects on international normalized ratio [INR] > 4.0, nonmajor bleeding, thrombotic outcomes, or overall mortality.
In the first month of genotype-guided warfarin therapy, compared with standard dosing, there were no improvements in % TTR, INR > 4.0, major or minor bleeding, thromboembolism, or all-cause mortality. There was a shorter TMD, and, after 1 month, improved % TTR and major bleeding incidence, making this a cost-effective strategy in patients requiring longer anticoagulation therapy.
华法林是一种广泛应用的抗凝剂，其疗效取决于包括基因型在内的多种患者因素。比较华法林基因导向给药（GD）与标准给药的随机对照试验（RCT）显示，疗效和安全性结果不一。我们对所有已发表的比较华法林不同适应证成年患者GD与标准给药的RCT进行了荟萃分析。
我们检索了MEDLINE、EMBASE、Cochrane对照试验中心注册库（CENTRAL）以及相关参考文献，以查找2014年3月之前发表的英文RCT。我们使用随机效应模型进行荟萃分析。
荟萃分析纳入了10项RCT，共2505例患者。与标准给药相比，GD在随访≤1个月时，治疗范围内时间百分比（TTR）相似（39.7%对40.2%；平均差[MD]，-0.52[95%CI，-3.15至2.10]；P = 0.70），在随访>1个月时，TTR百分比更高（59.4%对53%；MD，6.35[95%CI，1.76 - 10.95]；P = 0.007），在随访≤1个月时，大出血风险有降低趋势（风险比，0.46[95%CI，0.19 - 1.11]；P = 0.08），在随访>1个月时，大出血风险更低（0.34[95%CI，0.16 - 0.74]，P = 0.006），达到维持剂量的时间（TMD）更短（24.6天对34.1天；MD，-9.54天[95%CI，-18.10至-0.98]；P = 0.03），但对国际标准化比值[INR]>4.0、非大出血、血栓形成结局或总死亡率无影响。
在基因导向的华法林治疗的第一个月，与标准给药相比，TTR百分比、INR>4.0、大出血或小出血、血栓栓塞或全因死亡率均无改善。TMD更短，且在1个月后，TTR百分比和大出血发生率有所改善，这使其成为需要长期抗凝治疗患者的一种具有成本效益的策略。
