背景:抗血栓治疗,包括低分子量肝素(LMWH)或普通肝素(UFH),已被提议作为2019年冠状病毒病(COVID-19)的潜在疗法,以降低弥漫性血管内凝血激活。然而,目前尚不清楚预防或治疗剂量在降低死亡率方面是否具有相似的疗效.方法:我们进行了系统评价(PROSPERO注册CRD42020179955)和荟萃分析,包括观察性队列研究和随机对照试验(RCT)评估肝素的有效性(LMWH,UFH,或磺达肝素)在COVID-19患者中。肝素治疗与不抗凝治疗相比。进行了预防或治疗剂量与不抗凝相比的亚组分析。还将预防性剂量与全剂量抗凝比较。主要终点是全因死亡率。次要终点是大出血和住院时间(LOS)。结果:33项研究(31项观察性,2个RCT)被包括在32,688名患者的总人群中。其中,21,723(66.5%)是肝素。31项研究报告了全因死亡率的数据,显示预防性和全剂量均可降低死亡率(合并危险比[HR]0.63,95%置信区间[CI]分别为0.57-0.69和HR0.56,95%CI0.47-0.66).然而,与预防剂量相比,全剂量与较高的大出血风险相关(赔率比[OR]2.01,95%CI1.14~3.53).最后,在3项研究中评估了LOS;在有和没有肝素的患者之间没有观察到差异(0.98,-3.87,5.83天)。结论:全剂量和预防剂量的肝素均可有效降低住院COVID-19患者的死亡率,与没有治疗相比。然而,全剂量与出血风险增加相关.系统审查注册:https://clinicaltrials.gov/,标识符CRD42020179955。
Background: Antithrombotic treatment, including low molecular weight heparin (
LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality. Methods: We performed a systematic
review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either
LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS). Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14-3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, -3.87, 5.83 days). Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding. Systematic
Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955.