Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis.
Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis.
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Covid-19 患者强化预防性抗凝治疗与标准预防性抗凝治疗的疗效和安全性：系统评价和荟萃分析。
DOI：
10.1101/2022.03.05.22271947
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Wasserman,Sean
中科院分区：
文献类型：
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作者：
Wills,NicolaK;Nair,Nikhil;Patel,Kashyap;Sikder,Omaike;Adriaanse,Marguerite;Eikelboom,John;Wasserman,Sean
背景：随机对照试验（RCTs）报告了强化抗凝治疗对Covid-19临床结果的不一致影响。我们对现有试验的汇总数据进行了荟萃分析，以量化对非致命和致命结局的影响，并确定可能受益的亚组。方法检索多个数据库，比较截至2022年1月19日实验室确诊的成人Covid-19强化（中间或治疗剂量）抗凝治疗与标准预防剂量抗凝治疗的随机对照试验。主要疗效指标为随访结束或出院时的全因死亡率。我们使用随机效应荟萃分析来估计死亡率、血栓形成和出血事件的合并风险比，并对临床环境和强化抗凝剂量进行亚组分析。结果纳入11项随机对照试验（n = 5873）。与预防性抗凝相比，强化抗凝与45天内死亡率的降低无关：强化抗凝组有17.5%（501/2861）死亡，预防性抗凝组有18.8%（513/2734）死亡，相对风险（RR） 0.93；95%ci, 0.79 - 1.10。在亚组分析中，普通病房住院患者的死亡率可能有降低的信号，但精确度低且异质性高（5项研究；RR 0.84; 95% CI, 0.49 - 1.44; I2 = 75%），与在ICU进行的研究无显著差异（相互作用P = 0.51）。与预防相比，强化抗凝可降低静脉血栓栓塞的风险（8项研究；RR 0.53, 95%CI 0.41 - 0.69; I2 = 0%）。在亚组分析中，这种效应是由治疗剂量而不是中间剂量驱动的（相互作用P = 0.04）。使用强化抗凝治疗会增加大出血（RR 1.73, 95% CI 1.17 - 2.56），与剂量和临床环境没有相互作用。结论强化抗凝治疗对Covid-19住院成人的短期死亡率没有影响，并与出血风险增加有关。在非icu住院患者中观察到的静脉血栓栓塞风险降低和死亡率降低的趋势需要在其他随机对照试验中进行探索。
Background Randomised controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in Covid-19. We performed an aggregate data meta-analysis from available trials to quantify effect on non-fatal and fatal outcomes and identify subgroups who may benefit. Methods We searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) versus standard prophylactic dose anticoagulation in adults with laboratory-confirmed Covid-19 through 19 January 2022. The primary efficacy outcome was all-cause mortality at end of follow-up or discharge. We used random effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events, and performed subgroup analysis for clinical setting and dose of intensified anticoagulation. Results Eleven RCTs were included (n = 5873). Intensified anticoagulation was not associated with a reduction in mortality for up to 45 days compared with prophylactic anticoagulation: 17.5% (501/2861) died in the intensified anticoagulation group and 18.8% (513/2734) died in the prophylactic anticoagulation group, relative risk (RR) 0.93; 95%CI, 0.79 – 1.10. On subgroup analysis, there was a possible signal of mortality reduction for inpatients admitted to general wards, although with low precision and high heterogeneity (5 studies; RR 0.84; 95% CI, 0.49 – 1.44; I2 = 75%) and not significantly different to studies performed in the ICU (interaction P = 0.51). Risk of venous thromboembolism was reduced with intensified anticoagulation compared with prophylaxis (8 studies; RR 0.53, 95%CI 0.41 – 0.69; I2 = 0%). This effect was driven by therapeutic rather than intermediate dosing on subgroup analysis (interaction P = 0.04). Major bleeding was increased with use of intensified anticoagulation (RR 1.73, 95% CI 1.17 – 2.56) with no interaction for dosing and clinical setting. Conclusion Intensified anticoagulation has no effect on short term mortality among hospitalised adults with Covid-19 and is associated with increased risk of bleeding. The observed reduction in venous thromboembolism risk and trend towards reduced mortality in non-ICU hospitalised patients requires exploration in additional RCTs.