The Effect of Heparin Full-Dose Anticoagulation on Survival of Hospitalized, Non-critically Ill COVID-19 Patients: A Meta-analysis of High Quality Studies,Lung

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The Effect of Heparin Full-Dose Anticoagulation on Survival of Hospitalized, Non-critically Ill COVID-19 Patients: A Meta-analysis of High Quality Studies
Lung ( IF 4.6 ) Pub Date : 2023-02-04 , DOI: 10.1007/s00408-023-00599-6
Eros Pilia _{1,

2} , Alessandro Belletti ₃ , Stefano Fresilli ₃ , Todd C Lee ₄ , Alberto Zangrillo _{3,

5} , Gabriele Finco _{1,

2} , Giovanni Landoni _{3,

5} ,

Affiliation

Background

International COVID-19 guidelines recommend thromboprophylaxis for non-critically ill inpatients to prevent thrombotic complications. It is still debated whether full-dose thromboprophylaxis reduces all-cause mortality. The main aim of this updated systematic review and meta-analysis is to evaluate the effect of full-dose heparin-based thromboprophylaxis on survival in hospitalized non-critically ill COVID-19 patients.

Methods

A systematic review was performed across Pubmed/Medline, EMBASE, Cochrane Central Register of clinical trials, Clinicaltrials.gov, and medRxiv.org from inception to November 2022. We conducted a meta-analysis of randomized clinical trials (RCTs) comparing full-dose heparin-based anticoagulation to prophylactic or intermediate dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations Assessment, Development and Evaluation was applied. The primary outcome was all-cause mortality at the longest follow-up available.

Results

We identified 6 multicenter RCTs involving 3297 patients from 13 countries across 4 continents. The rate of all-cause mortality was 6.2% (103/1662) in the full-dose group vs 7.7% (126/1635) in the prophylactic or intermediate dose group (Risk Ratio [RR] = 0.76; 95% confidence interval [CI] = 0.59–0.98; P = 0.037). The probabilities of any mortality difference and of NNT ≤ 100 were estimated at 98.2% and 84.5%, respectively. The risk of bias was low for all included RCTs and the strength of the evidence was “moderate.”

Conclusion

Our meta-analysis of high-quality multicenter RCTs suggests that full-dose anticoagulation with heparin or low molecular weight heparin reduces all-cause mortality in hospitalized non-critically ill COVID-19 patients.

Study registration: PROSPERO, review no. CRD42022348993.

Graphical Abstract

中文翻译：

肝素全剂量抗凝对住院非重症 COVID-19 患者生存的影响：高质量研究的荟萃分析

背景

国际 COVID-19 指南建议对非重症住院患者进行血栓预防，以预防血栓并发症。全剂量血栓预防是否能降低全因死亡率仍有争议。本次更新的系统评价和荟萃分析的主要目的是评估基于全剂量肝素的血栓预防对住院非重症 COVID-19 患者生存的影响。

方法

从开始到 2022 年 11 月，对 Pubmed/Medline、EMBASE、Cochrane 临床试验中央注册中心、Clinicaltrials.gov 和 medRxiv.org 进行了系统评价。我们对随机临床试验 (RCT) 进行了荟萃分析，比较了全剂量在住院的非重症 COVID-19 患者中，基于肝素的抗凝到预防或中等剂量抗凝或标准治疗。使用用于随机试验的 Cochrane 偏倚风险工具评估偏倚风险，并应用推荐评估、制定和评估的分级。主要结局是最长随访时间内的全因死亡率。

结果

我们确定了 6 项多中心随机对照试验，涉及来自 4 大洲 13 个国家的 3297 名患者。全剂量组的全因死亡率为 6.2% (103/1662)，而预防或中剂量组为 7.7% (126/1635)（风险比 [RR] = 0.76；95% 置信区间 [ CI] = 0.59–0.98；P = 0.037）。任何死亡率差异和 NNT ≤ 100 的概率估计分别为 98.2% 和 84.5%。所有纳入的随机对照试验的偏倚风险都很低，证据强度为“中等”。