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急诊住院患者使用不同抗凝剂预防血栓形成的系统回顾和网络荟萃分析
作者:小柯机器人 发布时间:2022/7/8 14:17:25

荷兰格罗宁根大学Ruben J Eck团队对急诊住院患者预防血栓形成的抗凝剂进行了一项系统回顾和网络荟萃分析。该项研究成果发表在2022年7月4日出版的《英国医学杂志》上。

为了评估不同类型和剂量的抗凝药物对急诊住院患者预防静脉血栓栓塞的益处和危害,研究组在Cochrane CENTRAL、PubMed/Medline、Embase、科学引文索引、临床试验注册中心和国家卫生局数据库中检索从建库至2021年11月16日已发表和未发表的随机对照试验,这些试验评估了低剂量或中剂量低分子肝素、低剂量或中剂量普通肝素、直接口服抗凝剂、五糖、安慰剂或无干预措施对急诊住院成人患者静脉血栓栓塞的预防作用,对这些试验进行系统回顾和网络荟萃分析。

研究组对四个共同主要结局,即全因死亡率、症状性静脉血栓栓塞、大出血和90天或最接近90天的严重不良事件,进行随机效应、贝叶斯网络荟萃分析。使用Cochrane偏倚风险2.0工具评估偏倚风险。使用网络荟萃分析框架中的置信度对证据质量进行分级。

共确定44个随机对照试验,随机分配的90095名参与者被纳入主要分析。低至中等质量的证据表明,与安慰剂相比,这些干预措施均未降低全因死亡率。五糖(优势比0.32)、中剂量低分子肝素(0.66)、直接口服抗凝剂(0.68)和中剂量普通肝素(0.71)最有可能减少症状性静脉血栓栓塞(极低质量证据)。

中剂量普通肝素(2.63)和直接口服抗凝剂(2.31)最有可能增加大出血风险(低至中等质量证据)。关于严重不良事件(极低至低质量的证据),干预措施之间未发现结论性差异。与用安慰剂取代的不干预相比,所有积极干预在静脉血栓栓塞风险和死亡率方面更有利,而在大出血风险方面则不太有利。以上结果在预先指定的敏感性和亚组分析中是稳健的。

研究结果表明,中等剂量的低分子肝素在预防静脉血栓栓塞方面似乎具有最佳的利弊权衡。普通肝素,尤其是中剂量肝素和直接口服抗凝剂的效果最差。干预效果存在系统性差异,这取决于参考治疗是否为安慰剂。该研究的主要局限性包括证据质量,由于不精确和研究内偏差以及统计不一致性,证据质量通常较低至中等。

附:英文原文

Title: Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis

Author: Ruben J Eck, Tessa Elling, Alex J Sutton, Jrn Wetterslev, Christian Gluud, Iwan C C van der Horst, Reinold O B Gans, Karina Meijer, Frederik Keus

Issue&Volume: 2022/07/04

Abstract:

Objective To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.

Design Systematic review and network meta-analysis.

Data sources Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021.

Eligibility criteria for selecting studies Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital.

Main outcome measures Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework.

Results 44 randomised controlled trials that randomly assigned 90095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses.

Conclusions Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc.

DOI: 10.1136/bmj-2022-070022

Source: https://www.bmj.com/content/378/bmj-2022-070022

期刊信息

BMJ-British Medical Journal:《英国医学杂志》,创刊于1840年。隶属于BMJ出版集团,最新IF:27.604
官方网址:http://www.bmj.com/
投稿链接:https://mc.manuscriptcentral.com/bmj