Continuation of therapeutic anticoagulation before and during hospitalization is associated with reduced mortality in COVID-19 ICU patients

R. Choron, Stephen Iacono, Karishma Maharaja, Christopher D. Adams, Christopher A. Butts, C. Bargoud, Amanda L. Teichman, Nicole Krumrei, M. Schroeder, M. B. Bover Manderski, M. Rodricks, M. Lissauer, Rajan Gupta
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Abstract

Background: Literature has well established COVID-19 associated coagulopathy with resulting thrombotic complications including microthrombi as an underlying mechanism leading to severe respiratory disease. Therapeutic anticoagulation (TAC) for COVID-19 patients has therefore been widely trialed to combat COVID-19’s coagulopathic effects. However, literature has yet to define which population of patients TAC benefits; the most current randomized controlled trials (RCTs) reveal TAC to be possibly beneficial to moderately-ill hospitalized COVID-19 patients, whereas benefits did not outweigh risks in critically-ill ICU patients. Importantly, these studies excluded patients who received prehospital TAC. We examined outcomes in critically ill COVID-19 ICU patients who received TAC vs prophylactic anticoagulation (PAC) and specifically whether prehospital TAC effected outcomes. Methods: Retrospective cohort study of 132 COVID-19 ICU patients admitted March-June, 2020. Initial clinical practice provided PAC, as literature demonstrating COVID-19 associated coagulopathy and increased thromboembolic complications emerged, a TAC protocol was initiated. Results: 130 patients were included in the study, 95 of whom received TAC and 35 PAC. There was 50.8% overall mortality, with lower mortality in the TAC vs PAC group (46.3% vs 62.9%, p=0.094). There were few thromboembolic and hemorrhagic complications, with no significant difference between TAC and PAC patients. Of 24 patients anticoagulated prior to and during hospitalization, only 1 (4.2%) died, whereas the mortality was 60.6% among patients therapeutically anticoagulated during hospitalization only (p<0.001). Multivariable analysis revealed patients who received prehospital and in hospital TAC had a 92% lower risk of death (p=0.008) compared to in hospital only TAC and PAC patients. Conclusions: Overall, therapeutic anticoagulation did not result in mortality benefit to COVID-19 ICU patients compared to prophylactic anticoagulation. However, a sub-population of patients who received TAC both prior to and during hospitalization had a 12-fold lower risk of death. This suggests a protective effect of TAC when it is continued before and during hospitalization. RCTs are needed to specifically examine this subset of COVID-19 patients.
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住院前和住院期间继续治疗抗凝与COVID-19 ICU患者死亡率降低相关
背景:文献已经很好地证实了COVID-19相关凝血病与由此产生的血栓性并发症(包括微血栓)是导致严重呼吸系统疾病的潜在机制。因此,针对COVID-19患者的治疗性抗凝治疗(TAC)已被广泛试验,以对抗COVID-19的凝血功能。然而,文献尚未确定哪些患者群体的TAC受益;最新的随机对照试验(rct)显示,TAC可能对中度住院的COVID-19患者有益,而对重症ICU患者的益处并不大于风险。重要的是,这些研究排除了院前接受TAC的患者。我们检查了重症COVID-19 ICU患者接受TAC与预防性抗凝治疗(PAC)的结局,特别是院前TAC是否影响结局。方法:对2020年3 - 6月收治的132例COVID-19 ICU患者进行回顾性队列研究。最初的临床实践提供PAC,由于文献显示COVID-19相关凝血功能障碍和血栓栓塞并发症增加,因此启动了TAC方案。结果:纳入研究的130例患者中,95例患者接受TAC治疗,35例患者接受PAC治疗,总死亡率为50.8%,TAC组死亡率低于PAC组(46.3% vs 62.9%, p=0.094)。血栓栓塞和出血并发症很少,TAC和PAC患者之间无显著差异。在24例住院前和住院期间抗凝治疗的患者中,只有1例(4.2%)死亡,而仅住院期间治疗抗凝治疗的患者死亡率为60.6% (p<0.001)。多变量分析显示,与仅在医院接受TAC和PAC的患者相比,院前和院内接受TAC的患者死亡风险降低92% (p=0.008)。结论:总体而言,与预防性抗凝治疗相比,治疗性抗凝治疗并未使COVID-19 ICU患者的死亡率降低。然而,在住院前和住院期间接受TAC治疗的患者亚群死亡风险降低了12倍。这表明在住院前和住院期间继续使用TAC具有保护作用。需要进行随机对照试验来专门检查这部分COVID-19患者。
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