Background

Hospital-associated venous thromboembolism is a major patient safety concern. Provision of prophylaxis to patients admitted for elective total knee replacement surgery has been proposed as an effective strategy to reduce the incidence of venous thromboembolism. We aimed to assess the relative efficacy and safety of all available prophylaxis strategies in this setting.

Methods

We did a systematic review and Bayesian network meta-analyses of randomised controlled trials to assess the relative efficacy and safety of venous thromboembolism prophylaxis strategies and to populate an economic model that assessed the cost-effectiveness of these strategies and informed the updated National Institute for Health and Care Excellence (NICE) guideline recommendations for patients undergoing elective total knee replacement surgery. The Cochrane Library (CENTRAL), Embase, and Medline were last searched on June 19, 2017, with key terms relating to the population (venous thromboembolism and total knee replacement) and the interventions compared, including available pharmacological and mechanical interventions. Outcomes of interest were deep vein thrombosis (symptomatic and asymptomatic), pulmonary embolism, and major bleeding. Risk of bias was assessed, and relevant data extracted from the included randomised controlled trials for the network meta-analyses. Relative risks (RR; with 95% credible intervals [95% CrI]) compared to no prophylaxis, median ranks (with 95% CrI), and the probability of being the best intervention were calculated. The study was done in accordance with PRISMA guidelines.

Findings

25 randomised controlled trials were included in the network meta-analyses. 23 trials (19 interventions; n=15 028) were included in the deep vein thrombosis network, 12 in the pulmonary embolism network (13 interventions; n=15 555), and 19 in the major bleeding network (11 interventions; n=19 797). Risk of bias ranged from very low to high. Rivaroxaban ranked first for prevention of deep vein thrombosis (RR 0·12 [95% CrI 0·06–0·22]). Low molecular weight heparin (LMWH; standard prophylactic dose, 28–35 days) ranked first in the pulmonary embolism network (RR 0·02 [95% CrI 0·00–3·86]) and LMWH (low prophylactic dose, 10–14 days) ranked first in the major bleeding network (odds ratio 0·08 [95% CrI 0·00–1·76]), but the results for pulmonary embolism and major bleeding are highly uncertain.

Interpretation

Single prophylaxis strategies are more effective in prevention of deep vein thrombosis in the elective total knee replacement population than combination strategies, with rivaroxaban being the most effective. The results of the pulmonary embolism and major bleeding meta-analyses are uncertain and no clear conclusion can be made other than what is biologically plausible (eg, that no prophylaxis and mechanical prophylaxis strategies should have the lowest risk of major bleeding).

Funding

National Institute for Health and Care Excellence.

中文翻译：

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选择性全膝关节置换患者静脉血栓栓塞预防策略：系统评价和网络荟萃分析

背景

医院相关的静脉血栓栓塞是一个主要的患者安全问题。已提议为因择期全膝关节置换手术入院的患者提供预防措施，作为降低静脉血栓栓塞发生率的有效策略。我们旨在评估在这种情况下所有可用预防策略的相对有效性和安全性。

方法

我们对随机对照试验进行了系统评价和贝叶斯网络荟萃分析，以评估静脉血栓栓塞预防策略的相对有效性和安全性，并建立一个评估这些策略的成本效益的经济模型，并为更新后的美国国立卫生研究院提供信息和卓越护理 (NICE) 指南对接受选择性全膝关节置换手术的患者的建议。Cochrane Library (CENTRAL)、Embase 和 Medline 的最后一次检索是在 2017 年 6 月 19 日，其中包含与人群相关的关键术语（静脉血栓栓塞和全膝关节置换术）以及比较的干预措施，包括可用的药物和机械干预措施。感兴趣的结果是深静脉血栓形成（有症状和无症状）、肺栓塞和大出血。评估偏倚风险，并从纳入的随机对照试验中提取相关数据用于网络荟萃分析。计算相对风险（RR；95% 可信区间 [95% CrI]）与无预防相比，中位等级（95% CrI）和成为最佳干预的概率。该研究是根据 PRISMA 指南进行的。

发现

网络荟萃分析纳入了 25 项随机对照试验。23 项试验（19 项干预措施；n=15 028）被纳入深静脉血栓形成网络，12 项试验纳入肺栓塞网络（13 项干预措施；n=15 555），19 项试验纳入大出血网络（11 项干预措施；n=19 797)。偏倚风险从非常低到高不等。利伐沙班在预防深静脉血栓形成方面排名第一（RR 0·12 [95% CrI 0·06–0·22]）。低分子量肝素（LMWH；标准预防剂量，28-35 天）在肺栓塞网络（RR 0·02 [95% CrI 0·00-3·86]）和 LMWH（低预防剂量，10- 14 天）在大出血网络中排名第一（优势比 0·08 [95% CrI 0·00–1·76]），但肺栓塞和大出血的结果高度不确定。

解释

在选择性全膝关节置换人群中，单一预防策略在预防深静脉血栓形成方面比联合策略更有效，利伐沙班是最有效的。肺栓塞和大出血荟萃分析的结果是不确定的，除了生物学上的合理性（例如，没有任何预防和机械预防策略应该具有最低的大出血风险）之外，无法得出明确的结论。

资金

国家健康与护理卓越研究所。