Li Xiaoqi, Yang Jie, Wang Xuyun, Xu Qiang, Zhang Yuxiao, Yin Tong
Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Thromb Res. 2015 Apr;135(4):621-9. doi: 10.1016/j.thromres.2015.01.018. Epub 2015 Jan 17.
Pharmacogenetic (PG) algorithms were proposed to predict warfarin therapeutic dose more accurately. However, the clinical efficacy of the strategy over the standard treatment was not consistently proven.
We conducted a meta-analysis of the published randomized controlled trials (RCTs) comparing PG algorithm-based warfarin dosing (PG group) with clinical or standard protocols (STD group). The PUBMED, EMBASE, Cochrane Library and Web of Science databases were searched up to June 2014.
A total of 10 RCTs were retrieved for the meta-analysis with the inclusion of 2,601 participants. Primary analysis showed both major bleeding (2.65% versus 4.75%; RR: 0.57, 95% CI: 0.37- 0.90, P=0.02) and thromboembolic events (0.59% versus 1.88%; RR: 0.38, 95% CI: 0.17-0.85, P=0.02) were significantly lower in PG than in STD group. There was a trend towards increased percentage of time in therapeutic range (%TTR) [mean difference (MD): 4.65, 95% CI: 0.01- 9.29, P=0.05] in PG group, but no difference was observed for over-anticoagulation (INR>4). Subgroup analyses showed significant reduction of both major bleeding and thromboembolic events in PG group when the follow-up time was more than 1 month. After stratified by different PG algorithms, significant major bleeding reduction could be found in PG group when warfarin indication or co-medication of amiodarone was integrated in the algorithms.
PG algorithm-guided warfarin anticoagulation is beneficial for the reduction of both major bleeding and thromboembolic events compared with standard dosing strategy. The benefits may be prominent in patients with longer follow-up time, or guided by refined PG algorithms.
药物遗传学（PG）算法被提出用于更准确地预测华法林治疗剂量。然而，该策略相对于标准治疗的临床疗效尚未得到一致证实。
我们对已发表的随机对照试验（RCT）进行了荟萃分析，比较基于PG算法的华法林给药（PG组）与临床或标准方案（STD组）。检索了截至2014年6月的PUBMED、EMBASE、Cochrane图书馆和科学网数据库。
共检索到10项RCT用于荟萃分析，纳入2601名参与者。初步分析显示，PG组的大出血（2.65%对4.75%；RR：0.57，95%CI：0.37 - 0.90，P = 0.02）和血栓栓塞事件（0.59%对1.88%；RR：0.38，95%CI：0.17 - 0.85，P = 0.02）均显著低于STD组。PG组在治疗范围内的时间百分比（%TTR）有增加趋势[平均差异（MD）：4.65，95%CI：0.01 - 9.29，P = 0.05]，但在过度抗凝（INR>4）方面未观察到差异。亚组分析显示，当随访时间超过1个月时，PG组的大出血和血栓栓塞事件均显著减少。按不同PG算法分层后，当算法中纳入华法林适应证或胺碘酮联合用药时，PG组可显著降低大出血发生率。
与标准给药策略相比，PG算法指导的华法林抗凝治疗有利于减少大出血和血栓栓塞事件。在随访时间较长的患者中，或在精细的PG算法指导下，这些益处可能更为显著。
