Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (13): 2390-2398.doi: 10.3969/j.issn.2095-4344.2013.13.016
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Ruan Jia-li, Lü Tao, Miao Jing-jing, Chen Ming-yi, Han Zhong-yu, Tian Jing
Received:
2012-09-10
Revised:
2012-10-15
Online:
2013-03-26
Published:
2013-03-26
Contact:
Tian Jing, Professor, Associate chief physician, Master’s supervisor, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, Guangdong Province, China
tian_jing6723@yahoo.com.cn
About author:
Ruan Jia-li, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, Guangdong Province, China
weriamo@qq.com
CLC Number:
Ruan Jia-li, Lü Tao, Miao Jing-jing, Chen Ming-yi, Han Zhong-yu, Tian Jing. Dabigatran and rivaroxaban versus enoxaparin for anticoagulant therapy after total knee or hip arthroplasty[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(13): 2390-2398.
2.2.1 随机分配方法 除2个研究未明确提到具体的随机分配方法[17-18],具有选择性偏倚的中度可能性外,其余12个研究均提到了随机分配的具体方式[10-16,19-23],发生选择性偏倚的可能性低。 2.2.2 分配隐藏 有5个研究未明确提及运用了分配隐藏方案[12-13,19-20,23],有发生选择性偏倚的中度可能性。其他9个研究均采用分配隐藏方案[10-11,14-18,20-22],发生选择性偏倚的可能性低。 2.2.3 盲法 除3个研究未明确提及采用双盲法或单盲法实施试验[11,19,23],有发生实施偏倚或测量偏倚的中度可能性外,其余11个研究均采用双盲法实施[10,12-18,20-21],发生实施偏倚或测量偏倚的可能性低。 2.2.4 损耗性偏倚的评估 除1个研究未明确提及试验后随访及失访率/剔除率/退出率情况[10],有发生损耗性偏倚的中、高度可能性外,其余13个研究的试验后随访均较完善[11-23],失访率/剔除率/退出率均低于10%,发生耗损性偏倚的可能性低。 2.2.5 质量等级 根据以上质量评估,纳入的文献中质量为A级的有5篇[10,14,16,21-22],质量为B级的有9 篇[11-13,15,17-20,23],没有质量为C级的文献。 2.3 依诺肝素、达比加群、利伐沙班疗效的Meta分析 2.3.1 基础疗效的Meta分析 见图1。"
如图1所示,关于新型抗凝药达比加群和利伐沙班与依诺肝素对于全髋或全膝置换后抗凝疗效的评估方面,纳入并分析了14篇文献共17 212例患者,各研究之间有明显的异质性(χ2=101.93,P < 0.000 01,I2=87%),结果表明新药组明显优于依诺肝素组[RR=0.66,95%CI(0.51-0.85)]。 达比加群的总血栓发生率和死亡率:5篇文献共纳入 6 213例患者;各研究之间差异有显著性意义(χ2= 17.28,P=0.002,I2=77%),结果表明达比加群(220 mg, 1次/d)与依诺肝素(40 mg,1次/d)疗效差异无显著性意义[RR=0.90,95%CI(0.71-1.14)]。 利伐沙班的总血栓发生率和死亡率:9篇文献共纳入 10 999例患者;各研究之间差异具有显著性意义 (χ2=44.03,P < 0.000 01,I2=82%),结果表明利伐沙班(10 mg,1次/d)与依诺肝素(40 mg,1次/d)疗效差异有显著性意义[RR=0.54,95%CI(0.38-0.76)]。 2.3.2 主要静脉血栓形成率的Meta分析 见图2。"
达比加群的主要静脉血栓发生率:4篇文献共纳入 5 715例患者;各研究间无明显异质性(χ2=5.86,P=0.12,I2=49%),结果表明达比加群(220 mg,1次/d)和依诺肝素(40 mg,1次/d)组主要静脉血栓发生率差异无显著性意义[RR=0.78,95%CI(0.52-1.17)]。 利伐沙班的主要静脉血栓发生率:8篇文献共纳入 10 789例患者;各研究间存在较大异质性(χ2=25.34,P=0.000 7,I2=72%),结果表明利伐沙班(40 mg, 1次/d)比依诺肝素(40 mg,1次/d)组主要静脉血栓发生率低[RR=039,95%CI(0.19-0.78)]。 新药组主要静脉血栓发生率:12篇文献共纳入16 504例患者;各研究间存在明显异质性(χ2= 41.28,P < 0.000 01,I2=73%),结果表明新药组[利伐沙班(10 mg,1次/d)和达比加群(220 mg,1次/d)]比常规(依诺肝素)治疗法主要静脉血栓发生率低[RR=0.52,95%(0.33-0.83)]。 2.3.3 深静脉血栓形成率的Meta分析 见图3。"
达比加群的深静脉血栓形成率:5篇文献共纳入6 224例患者;各研究间无明显异质性(χ2=6.06,P=0.19,I2=34%),结果表明达比加群(220 mg,1次/d)较依诺肝素(40 mg,1次/d)组深静脉血栓发生率低[RR=0.69,95%CI(0.52-0.92)]。 利伐沙班的深静脉血栓发生率:7篇文献共纳入9 029例患者;各研究间存在明显异质性(χ2=37.78,P < 0.000 01,I2=84%),结果表明利伐沙班(10 mg,1次/d)较依诺肝素(40 mg,1次/d)组深静脉血栓发生率低[RR=0.51,95%CI (0.34-0.78)]。 新药组深静脉血栓发生率:12篇文献共纳入15 253例患者;各研究间存在明显异质性(χ2=45.26,P < 0.000 01,I2=76%)。结果表明新药组较传统治疗(依诺肝素40 mg, 1次/d)深静脉血栓发生率低[RR=0.59,95%CI (0.45-0.78)]。 2.3.4 肺血栓栓塞形成率的Meta分析 见图4。"
达比加群的肺血栓栓塞形成率:3篇文献共纳入5 519例患者;各研究间无明显异质性(χ2=0.73,P=0.69,I2=0%),结果表明达比加群(220 mg,1次/d)与依诺肝素(40 mg,1次/d)组肺静脉血栓发生率差异无显著性意义[RR=1.24,95%CI(0.53-2.88)]。 利伐沙班的肺血栓栓塞发生率:6篇文献共纳入10 802例患者;各研究间无明显异质性(χ2=4.74,P=0.19,I2=37%),结果表明利伐沙班(10 mg,1次/d)与依诺肝素(40 mg,1次/d)组肺静脉血栓发生率差异无显著性意义[RR=0.54,95%CI (0.24-1.19]。 新药组的肺血栓栓塞发生率:12篇文献共纳入16 321例患者;各研究间无明显异质性(χ2=7.24,P=0.30,I2=17%),结果表明新药组与传统治疗(依诺肝素40 mg, 1次/d)肺静脉血栓发生率差异无显著性意义[RR=0.79,95%CI(0.45-1.39]。 2.3.5 有症状的深静脉血栓发生率的Meta分析 见图5。 达比加群的有症状深静脉血栓形成率:2篇文献共纳入 3 526例患者;各研究间存在明显异质性(χ2=2.49,P=0.11,I2=60%),结果表明达比加群(220 mg,1次/d)和依诺肝素(40 mg,1次/d)组主要静脉血栓发生率差异无显著性意义[RR=1.89,95%CI(0.29-12.26)]。 利伐沙班的有症状深静脉血栓发生率:6篇文献共纳入12 500例患者;各研究间无明显异质性(χ2=3.45,P=0.63,I2=0%),结果表明利伐沙班(10 mg,1次/d)较依诺肝素(40 mg,1次/d)组有症状的深静脉血栓发生率低[RR=0.49,95%CI (0.34-0.72)]。 新药组的有症状深静脉血栓发生率:8篇文献共纳入 16 026例患者;各研究间无明显异质性(χ2=9.32,P=0.23,I2=25%),结果表明新药组有症状的深静脉血栓较传统治疗(依诺肝素组)发生率低[RR=0.57,95%CI (0.36-0.90)]。"
2.4 依诺肝素,达比加群,利伐沙班安全性的Meta分析 2.4.1 用药后大出血发生率的Meta分析 见图6。 达比加群用药后大出血的发生率:4篇文献共纳入7 411例患者;各研究组无明显异质性(χ2=4.17,P=0.24,I2=28%),结果表明达比加群(220 mg,1次/d)组与依诺肝素(40 mg,1次/d)组在大出血发生率上差异无显著性意义[RR=1.09,95%CI(0.74-1.61)]。 利伐沙班用药后大出血的发生率:8篇文献共纳入 13 432例患者;各研究组间无明显异质性(χ2=4.84,P=0.56,I2=0%),结果表明利伐沙班(10 mg,1次/d)组与依诺肝素(40 mg,1次/d)组在大出血发生率上差异无显著性意义[RR=1.69,95%CI(0.96-2.98)]。 新药组用药后大出血的发生率:12篇文献共纳入20 843例患者;各研究组之间无明显异质性(χ2=10.24,P=0.16,I2=2%),结果表明新药组与传统治疗在用药后大出血的发生率上差异无显著性意义[RR=1.26,95%CI (0.91-1.73)]。"
达比加群临床相关的少量出血的发生率:4篇文献共纳入7 411例患者;各研究组无明显异质性(χ2=0.10,P=0.99,I2=0%),结果表明达比加群(220 mg,1次/d)组与依诺肝素(40 mg,1次/d)组在临床相关少量出血发生率差异无显著性意义[RR=1.15,95%CI(0.90-1.46)]。 利伐沙班临床相关的少量出血的发生率:8篇文献共纳入13 432例患者;各研究组间无明显异质性(χ2=2.87,P=0.90,I2=0%),结果表明利伐沙班(10 mg,1次/d)组与依诺肝素(40 mg,1次/d)组在临床相关少量出血发生率上差异无显著性意义[RR=1.21,95%CI(0.98-1.49)]。 新药组临床相关的少量出血的发生率:12篇文献共纳入20 843例患者;各研究组之间无明显异质性(χ2=3.07,P=0.99,I2=0%),结果表明新药组与传统治疗在用药后大出血的发生率上差异无显著性意义[RR=1.18,95%CI (1.01-1.39)]。 2.5 敏感性分析 鉴于文献质量的异质性和临床实验数据的选择,可能使统计结果产生一定的偏倚。作者对该荟萃分析进行了敏感性分析,结论如下:仅纳入明确采用盲法的随机对照试验,不会使本荟萃分析的有效性和安全性产生明显差异;剔除低级质量的文献后重新进行统计学分析不影响荟萃分析的最终结果;若同时纳入30,40 mg剂量组的依诺肝素进行比较,分析所得有效性和安全性差异无显著性意义。由此,可以认为该荟萃分析纳入的临床试验之间的异质性对所需的统计结果造成的偏倚在可接受范围之内。"
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