The Effect of Heparinoid as Systemic Prophylactic Anticoagulants on COVID-19 Patient Mortality and Its Safety Profiles: A Systematic Review and Meta-Analysis
Ariska Deffy Anggarany, M. Alkaff, Famila Takhwifa, H. Nufus, Diana Paramita
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Abstract
Coagulopathy is one of the complications of COVID-19 and is associated with a higher risk of mortality. However, evidence regarding the effectiveness and safety of anticoagulant therapy in various doses among COVID-19 patients is limited. This systematic review and meta-analysis aims to review and explore the effect of using heparinoids as a systemic anticoagulant at prophylactic doses on mortality in COVID-19 patients. Systematic searches were conducted of various databases (Pubmed, ScienceDirect, SpringerLink, Scopus, and ProQuest) covering the period 2019-2021. We assessed the quality of the articles using the STROBE checklist. Studies with a high risk of bias were excluded before pooled effect size was synthesized with 95% confidence intervals (CI) using random-effects models. From the 12 identified studies (N=8,968), six observational studies (N=7,176) were involved in the meta-analysis. The studies reviewed in the paper used a retrospective cohort design in various settings. The pooled effect size of mortality comparing prophylactic anticoagulant and no anticoagulant in three studies showed that there was an association between using prophylactic anticoagulant and a lower risk of in-hospital mortality (pooled OR= 0.47; 95% CI 0.19-0.76). A prophylactic dose of heparinoid anticoagulant was also associated with lower mortality (pooled OR= 0.51; 95% CI 0.21-0.82) and with lower bleeding events compared to intermediate-to-therapeutic dose anticoagulants. Administration of heparinoid anticoagulants at prophylactic doses was associated with reduced mortality risk in hospitalized COVID-19 patients. Due to the increased risk of bleeding with therapeutic doses, the use of prophylaxis anticoagulant is suggested in COVID-19 patients who are not critically ill.
凝血功能障碍是COVID-19的并发症之一,与较高的死亡风险相关。然而,关于不同剂量的抗凝治疗在COVID-19患者中的有效性和安全性的证据有限。本系统综述和荟萃分析旨在回顾和探讨肝素类药物作为系统性抗凝剂预防剂量对COVID-19患者死亡率的影响。系统检索了2019-2021年期间的各种数据库(Pubmed、ScienceDirect、SpringerLink、Scopus和ProQuest)。我们使用STROBE检查表评估文章的质量。在使用随机效应模型以95%置信区间(CI)综合效应大小之前,排除了高偏倚风险的研究。从12项确定的研究(N=8,968)中,有6项观察性研究(N=7,176)纳入了meta分析。论文中回顾的研究采用了不同环境下的回顾性队列设计。三项研究中比较预防性抗凝剂和不使用抗凝剂的死亡率的综合效应大小显示,使用预防性抗凝剂与较低的院内死亡风险之间存在关联(综合OR= 0.47;95% ci 0.19-0.76)。预防性剂量的类肝素抗凝剂也与较低的死亡率相关(合并OR= 0.51;95% CI 0.21-0.82),与中剂量至治疗剂量抗凝剂相比,出血事件更低。预防剂量的类肝素抗凝剂与住院COVID-19患者死亡风险降低相关。由于治疗剂量的出血风险增加,建议对非危重患者使用预防性抗凝血剂。