Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

被引：537

作者：

Lawler, Patrick R. ^{[1
,2
]}

Golighe, Ewan C. ^{[2
,3
]}

Berge, Jeffrey S. ^{[21
]}

Neal, Matthew D. ^{[29
,30
,54
]}

McVerry, Bryan J. ^{[29
,30
,65
]}

Nicolau, Jose C. ^{[34
]}

Gong, Michelle N. ^{[26
,27
]}

Carrier, Marc ^{[7
,8
]}

Rosenson, Robert S. ^{[22
,23
]}

Reynolds, Harmony R. ^{[21
]}

Turgeon, Alexis F. ^{[10
,11
]}

Escobedo, Jorge ^{[43
]}

Huang, David T. ^{[29
]}

Bradbury, Charlotte A. ^{[44
,45
]}

Houston, Brett L. ^{[12
,13
]}

Kornblith, Lucy Z. ^{[58
]}

Kumar, Anand ^{[12
]}

Kah, Susan R. n ^{[15
]}

Cushman, Mary ^{[64
]}

McQuilten, Zoe ^{[65
]}

Slutsky, Arthur S. ^{[2
,4
]}

Kim, Keri S. ^{[70
]}

Gordon, Anthony C. ^{[46
,47
]}

Kirwan, Bridget-Anne ^{[48
,74
]}

Brooks, Maria M. ^{[29
]}

Higgins, Alisa M. ^{[65
]}

Lewis, Roger J. ^{[59
,76
]}

Lorenzi, Elizabeth ^{[76
]}

Berry, Scott M. ^{[76
]}

Berry, Lindsay R. ^{[76
]}

Angus, Derek C. ^{[29
,30
]}

McArthur, Colin J. ^{[65
,79
,81
]}

Webb, Steven A. ^{[65
,67
]}

Farkouh, Michael E. ^{[1
,2
,58
]}

Hochman, Judith S. ^{[21
]}

Zarychanski, Ryan ^{[12
,13
]}

Aday, Aaron W. ^{[82
]}

Al-Beidh, Farah ^{[46
]}

Annane, Djillali ^{[84
]}

Arabi, Yaseen M. ^{[86
,87
]}

Aryal, Diptesh ^{[88
,89
]}

Kreuziger, Lisa Baumann ^{[90
]}

Beane, Abi ^{[92
]}

Bhimani, Zahra ^{[4
]}

Bihari, Shailesh ^{[69
]}

Billett, Henny H. ^{[26
,27
]}

Bond, Lindsay ^{[5
]}

Bonten, Marc ^{[93
]}

Brunkhorst, Frank ^{[95
]}

Buxton, Meredith ^{[60
]}

机构：

[1] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada

[2] Univ Toronto, Toronto, ON, Canada

[3] Univ Hlth Network, Toronto, ON, Canada

[4] St Michaels Hosp Unity Hlth, Toronto, ON, Canada

[5] Ozmosis Res, Toronto, ON, Canada

[6] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[7] Ottawa Hosp Res Inst, Ottawa, ON, Canada

[8] Inst Savoir Montfort, Ottawa, ON, Canada

[9] Univ Ottawa, Ottawa, ON, Canada

[10] Univ Laval, Quebec City, PQ, Canada

[11] CHU Quebec Univ Laval Res Ctr, Quebec City, PQ, Canada

[12] Univ Manitoba, Winnipeg, MB, Canada

[13] CancerCare Manitoba, Winnipeg, MB, Canada

[14] St Boniface Gen Hosp, Winnipeg, MB, Canada

[15] McGill Univ, Montreal, PQ, Canada

[16] McMaster Univ, Hamilton, ON, Canada

[17] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada

[18] Univ Sherbrooke, Sherbrooke, PQ, Canada

[19] Univ British Columbia, Vancouver, BC, Canada

[20] Univ Alberta, Edmonton, AB, Canada

[21] NYU Langone Hlth, NYU Grossman Sch Med, New York, NY USA

[22] NYU Langone Hlth, Icahn Sch Med Mt Sinai, New York, NY USA

[23] NYU Langone Hlth, Mt Sinai Heart, New York, NY USA

[24] NYU Langone Hosp, New York, NY USA

[25] Bellevue Hosp, New York, NY USA

[26] Montefiore Med Ctr, Bronx, NY USA

[27] Albert Einstein Coll Med, Bronx, NY 10467 USA

[28] NYU Langone Long Isl, Mineola, NY USA

[29] Univ Pittsburgh, Pittsburgh, PA USA

[30] UPMC, Pittsburgh, PA USA

[31] Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illness CRI, Pittsburgh, PA USA

[32] UPMC Childrens Hosp Pittsburgh, Pittsburgh, PA USA

[33] Penn State Hershey Med Ctr, Emergency Med, Hershey, PA USA

[34] Univ Sao Paulo, Hosp Clin, Fac Med, Inst Coracao, Sao Paulo, SP, Brazil

[35] Avanti Pesquisa Clin, Sao Paulo, Brazil

[36] Hosp Julho, Sao Paulo, Brazil

[37] Hosp Coracao, Sao Paulo, Brazil

[38] Hosp Cora Mato Grosso do Sul, Campo Grande, MS, Brazil

[39] Univ Fed Mato Grosso do Sul, Campo Grande, MS, Brazil

[40] Hosp Univ Maria Aparecida Pedrossia, Campo Grande, MS, Brazil

[41] Hosp Unimed Campo Grande, Campo Grande, MS, Brazil

[42] Clin Res Ctr, INGOH, Goiania, Go, Brazil

[43] Inst Mexicano Seguro Social, Mexico City, DF, Mexico

[44] Univ Bristol, Bristol, Avon, England

[45] Univ Hosp Bristol & Weston NHS Fdn Trust, Bristol, Avon, England

[46] Imperial Coll London, London, England

[47] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England

[48] London Sch Hyg & Trop Med, London, England

[49] Univ Coll London Hosp, London, England

[50] Kings Healthcare Partners, London, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2021年 / 385卷 / 09期

基金：

英国医学研究理事会; 加拿大健康研究院; 英国惠康基金; 美国国家卫生研究院; 欧盟地平线“2020”;

关键词：

D O I：

10.1056/NEJMoa2105911

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. 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. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline D-dimer level. RESULTS The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high D-dimer cohort, 92.9% in the low D-dimer cohort, and 97.3% in the unknown D-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.

引用

页码：790 / 802

页数：13

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