加拿大麦克马斯特大学Maura Marcucci团队研究了非心脏手术患者直接口服抗凝剂和低分子肝素预防血栓形成的利弊。相关论文于2022年3月9日发表在《英国医学杂志》上。
为了系统比较直接口服抗凝剂和低分子肝素预防血栓形成对非心脏手术患者的利弊，研究组在MEDLINE、EMABASE和Cochrane中央对照试验登记册中检索从建库至2021年8月的文献，对相关随机对照试验进行系统回顾和网络荟萃分析。
选择接受非心脏手术的成年人进行随机对照试验，比较低分子量肝素（预防性[低]或更高剂量）与直接口服抗凝剂或未进行积极治疗的预后。主要结局为症状性静脉血栓栓塞、症状性肺栓塞和大出血。
系统评价和荟萃分析（PRISMA）指南的首选报告项目用于网络荟萃分析。摘要和全文独立筛选，一式两份。从研究参与者、干预措施和结果中提取数据，并对偏倚风险进行独立评估，一式两份。多变量随机效应模型的频度网络荟萃分析提供了95%置信区间的优势比，等级评估表明了证据的确定性。
该研究共纳入68项随机对照试验（51例骨科、10例普通科、4例妇科、2例胸科和1例泌尿外科），共45445名患者。低剂量（优势比0.33）和高剂量（0.19）低分子肝素，以及直接口服抗凝剂（0.17）与无积极治疗相比，减少了症状性静脉血栓栓塞，根据基线风险（中高确定性证据），绝对风险差异为1-100/1000患者。
没有一种活性药物能减少症状性肺栓塞（中低确定性证据）。直接口服抗凝剂和低分子量肝素与未经积极治疗（中高确定性证据）相比，大出血的几率增加2-3倍，高危患者的绝对风险差异高达50/1000患者。
与低剂量低分子肝素相比，高剂量低分子肝素并未减少症状性静脉血栓栓塞（0.57），但增加了大出血（1.87）；直接口服抗凝剂可减少症状性静脉血栓栓塞（0.53），且不会增加大出血（1.23）。
研究结果表明，与未进行积极治疗相比，直接口服抗凝剂和低分子量肝素可减少静脉血栓栓塞，但可能会增加大出血，程度相似。直接口服抗凝剂可能比预防性低分子肝素更能预防症状性静脉血栓栓塞。
附：英文原文
Title: Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials
Author: Maura Marcucci, Itziar Etxeandia-Ikobaltzeta, Stephen Yang, Federico Germini, Shyla Gupta, Arnav Agarwal, Matthew Ventresca, Shaowen Tang, Gian Paolo Morgano, Mengxiao Wang, Muhammad Muneeb Ahmed, Ignacio Neumann, Ariel Izcovich, Juan Criniti, Federico Popoff, P J Devereaux, Philipp Dahm, David Anderson, Lauri I Lavikainen, Kari A O Tikkinen, Gordon H Guyatt, Holger J Schünemann, Philippe D Violette
Issue&Volume: 2022/03/09
Abstract:
Objective To systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery.
Design Systematic review and network meta-analysis of randomised controlled trials.
Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), up to August 2021.
Review methods Randomised controlled trials in adults undergoing non-cardiac surgery were selected, comparing low molecular weight heparin (prophylactic (low) or higher dose) with direct oral anticoagulants or with no active treatment. Main outcomes were symptomatic venous thromboembolism, symptomatic pulmonary embolism, and major bleeding. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for network meta-analyses. Abstracts and full texts were screened independently in duplicate. Data were abstracted on study participants, interventions, and outcomes, and risk of bias was assessed independently in duplicate. Frequentist network meta-analysis with multivariate random effects models provided odds ratios with 95% confidence intervals, and GRADE (grading of recommendations, assessment, development, and evaluation) assessments indicated the certainty of the evidence.
Results 68 randomised controlled trials were included (51 orthopaedic, 10 general, four gynaecological, two thoracic, and one urological surgery), involving 45445 patients. Low dose (odds ratio 0.33, 95% confidence interval 0.16 to 0.67) and high dose (0.19, 0.07 to 0.54) low molecular weight heparin, and direct oral anticoagulants (0.17, 0.07 to 0.41) reduced symptomatic venous thromboembolism compared with no active treatment, with absolute risk differences of 1-100 per 1000 patients, depending on baseline risks (certainty of evidence, moderate to high). None of the active agents reduced symptomatic pulmonary embolism (certainty of evidence, low to moderate). Direct oral anticoagulants and low molecular weight heparin were associated with a 2-3-fold increase in the odds of major bleeding compared with no active treatment (certainty of evidence, moderate to high), with absolute risk differences as high as 50 per 1000 in patients at high risk. Compared with low dose low molecular weight heparin, high dose low molecular weight heparin did not reduce symptomatic venous thromboembolism (0.57, 0.26 to 1.27) but increased major bleeding (1.87, 1.06 to 3.31); direct oral anticoagulants reduced symptomatic venous thromboembolism (0.53, 0.32 to 0.89) and did not increase major bleeding (1.23, 0.89 to 1.69).
Conclusions Direct oral anticoagulants and low molecular weight heparin reduced venous thromboembolism compared with no active treatment but probably increased major bleeding to a similar extent. Direct oral anticoagulants probably prevent symptomatic venous thromboembolism to a greater extent than prophylactic low molecular weight heparin.
DOI: 10.1136/bmj-2021-066785
Source: https://www.bmj.com/content/376/bmj-2021-066785
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：93.333
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本期文章：《英国医学杂志》：Online/在线发表
