Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.
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DOI：
10.1056/nejmoa2103417
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发表时间：
2021-08-26
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通讯作者：
Zarychanski R
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REMAP-CAP Investigators;ACTIV-4a Investigators;ATTACC Investigators;Goligher EC;Bradbury CA;McVerry BJ;Lawler PR;Berger JS;Gong MN;Carrier M;Reynolds HR;Kumar A;Turgeon AF;Kornblith LZ;Kahn SR;Marshall JC;Kim KS;Houston BL;Derde LPG;Cushman M;Tritschler T;Angus DC;Godoy LC;McQuilten Z;Kirwan BA;Farkouh ME;Brooks MM;Lewis RJ;Berry LR;Lorenzi E;Gordon AC;Ahuja T;Al-Beidh F;Annane D;Arabi YM;Aryal D;Baumann Kreuziger L;Beane A;Bhimani Z;Bihari S;Billett HH;Bond L;Bonten M;Brunkhorst F;Buxton M;Buzgau A;Castellucci LA;Chekuri S;Chen JT;Cheng AC;Chkhikvadze T;Coiffard B;Contreras A;Costantini TW;de Brouwer S;Detry MA;Duggal A;Džavík V;Effron MB;Eng HF;Escobedo J;Estcourt LJ;Everett BM;Fergusson DA;Fitzgerald M;Fowler RA;Froess JD;Fu Z;Galanaud JP;Galen BT;Gandotra S;Girard TD;Goodman AL;Goossens H;Green C;Greenstein YY;Gross PL;Haniffa R;Hegde SM;Hendrickson CM;Higgins AM;Hindenburg AA;Hope AA;Horowitz JM;Horvat CM;Huang DT;Hudock K;Hunt BJ;Husain M;Hyzy RC;Jacobson JR;Jayakumar D;Keller NM;Khan A;Kim Y;Kindzelski A;King AJ;Knudson MM;Kornblith AE;Kutcher ME;Laffan MA;Lamontagne F;Le Gal G;Leeper CM;Leifer ES;Lim G;Gallego Lima F;Linstrum K;Litton E;Lopez-Sendon J;Lother SA;Marten N;Saud Marinez A;Martinez M;Mateos Garcia E;Mavromichalis S;McAuley DF;McDonald EG;McGlothlin A;McGuinness SP;Middeldorp S;Montgomery SK;Mouncey PR;Murthy S;Nair GB;Nair R;Nichol AD;Nicolau JC;Nunez-Garcia B;Park JJ;Park PK;Parke RL;Parker JC;Parnia S;Paul JD;Pompilio M;Quigley JG;Rosenson RS;Rost NS;Rowan K;Santos FO;Santos M;Santos MO;Satterwhite L;Saunders CT;Schreiber J;Schutgens REG;Seymour CW;Siegal DM;Silva DG Jr;Singhal AB;Slutsky AS;Solvason D;Stanworth SJ;Turner AM;van Bentum-Puijk W;van de Veerdonk FL;van Diepen S;Vazquez-Grande G;Wahid L;Wareham V;Widmer RJ;Wilson JG;Yuriditsky E;Zhong Y;Berry SM;McArthur CJ;Neal MD;Hochman JS;Webb SA;Zarychanski R
血栓形成和炎症可能导致2019冠状病毒病（Covid-19）患者的发病率和死亡率。我们假设治疗剂量抗凝可以改善Covid-19危重患者的预后。在一项开放标签、适应性、多平台、随机临床试验中，重症Covid-19危重患者被随机分配到实际定义的治疗剂量肝素抗凝治疗方案或根据当地常规护理的药物血栓预防治疗方案。主要终点是无器官支持天数，以综合住院死亡（赋值为- 1）和存活至出院的患者在第21天无心血管或呼吸器官支持天数的顺序量表进行评估。当治疗剂量抗凝治疗达到预先规定的无效标准时，试验停止。1098例患者的主要结局数据可用（534例分配给治疗剂量抗凝治疗，564例分配给常规护理血栓预防治疗）。在接受治疗剂量抗凝治疗的患者中，无器官支持天数的中位数为1（四分位数范围，- 1至16），在接受常规护理的血栓预防患者中，无器官支持天数的中位数为4（四分位数范围，- 1至16）（调整比例优势比，0.83；95%可信区间，0.67至1.03；无效后验概率[定义为优势比<1.2],99.9%）。两组患者存活至出院的百分比相似（分别为62.7%和64.5%；校正优势比为0.84；95%可信区间为0.64 ~ 1.11）。分配给治疗剂量抗凝治疗的患者中有3.8%发生大出血，分配给常规药物血栓预防治疗的患者中有2.3%发生大出血。在Covid-19危重患者中，与常规护理药物血栓预防治疗相比，初始治疗剂量肝素抗凝治疗并不会导致更大的生存到出院的可能性或更长的无心血管或呼吸器官支持的天数。（REMAP-CAP、ACTIV-4a和ATTACC ClinicalTrials.gov编号：NCT02735707、NCT04505774、NCT04359277和NCT04372589）
Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.)