College of Pharmacy, Western University of Health Sciences, Pomona, CA.
Department of Medicine, McGill University, Montreal, QC, Canada.
Chest. 2011 Aug;140(2):374-381. doi: 10.1378/chest.10-3084. Epub 2011 Feb 24.
In medical patients, it is unclear whether thromboprophylaxis with low-dose unfractionated heparin (UFH) should be administered bid or tid.
This study was a mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk for VTE and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one another or to an inactive control subject. DVT, pulmonary embolism (PE), major bleeding, and death were measured. A Bayesian framework using a random-effects model was applied.
Sixteen trials with moderate methodologic quality enrolling 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89 (0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes.
Moderate-quality evidence suggests that subcutaneous UFH bid and UFH tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.
在医学患者中，低剂量未分级肝素（UFH）的预防性抗血栓治疗每日两次（bid）或每日三次（tid）给药的效果尚不清楚。
本研究为一项混合治疗比较的荟萃分析，纳入了有静脉血栓栓塞（VTE）风险的住院非手术患者，并比较了 UFH bid、UFH tid、或低分子肝素（LMWH）与彼此或与无活性对照之间的差异。评估了深静脉血栓形成（DVT）、肺栓塞（PE）、大出血和死亡。采用贝叶斯框架，使用随机效应模型进行分析。
16 项具有中等方法学质量的试验共纳入了 27667 名患者，为该分析提供了数据。与 UFH bid 相比，UFH tid 用于预防 DVT、PE、死亡和大出血的相对风险和 95%可信区间分别为 1.56（0.64-4.33）、1.67（0.49-208.09）、1.17（0.72-1.95）和 0.89（0.08-7.05）。与任何一种剂量的 UFH 相比，LMWH 的使用在所有四项结局上的效果与 UFH 相似。
中等质量证据表明，皮下 UFH bid 和 UFH tid 在预防 DVT、PE、大出血和死亡率方面的效果没有差异。UFH 的两种给药方案或 LMWH 都似乎是医学患者预防性抗血栓治疗的合理策略。考虑到要证明存在的差异（如果存在的话，无疑是很小的），需要进行非常大的样本量随机试验来比较这两种 UFH 剂量，这种试验非常不可能进行。
