Медицинская библиотека · The New England journal of medicine · 2021

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

ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Lawler Patrick R, Goligher Ewan C, Berger Jeffrey S, Neal Matthew D, McVerry Bryan J, Nicolau Jose C, Gong Michelle N, Carrier Marc, Rosenson Robert S, Reynolds Harmony R, Turgeon Alexis F, Escobedo Jorge, Huang David T, Bradbury Charlotte A, Houston Brett L, Kornblith Lucy Z, Kumar Anand, Kahn Susan R, Cushman Mary, McQuilten Zoe, Slutsky Arthur S, Kim Keri S, Gordon Anthony C, Kirwan Bridget-Anne, Brooks Maria M, Higgins Alisa M, Lewis Roger J, Lorenzi Elizabeth, Berry Scott M, Berry Lindsay R, Aday Aaron W, Al-Beidh Farah, Annane Djillali, Arabi Yaseen M, Aryal Diptesh, Baumann Kreuziger Lisa, Beane Abi, Bhimani Zahra, Bihari Shailesh, Billett Henny H, Bond Lindsay, Bonten Marc, Brunkhorst Frank, Buxton Meredith, Buzgau Adrian, Castellucci Lana A, Chekuri Sweta, Chen Jen-Ting, Cheng Allen C, Chkhikvadze Tamta, Coiffard Benjamin, Costantini Todd W, de Brouwer Sophie, Derde Lennie P G, Detry Michelle A, Duggal Abhijit, Džavík Vladimír, Effron Mark B, Estcourt Lise J, Everett Brendan M, Fergusson Dean A, Fitzgerald Mark, Fowler Robert A, Galanaud Jean P, Galen Benjamin T, Gandotra Sheetal, García-Madrona Sebastian, Girard Timothy D, Godoy Lucas C, Goodman Andrew L, Goossens Herman, Green Cameron, Greenstein Yonatan Y, Gross Peter L, Hamburg Naomi M, Haniffa Rashan, Hanna George, Hanna Nicholas, Hegde Sheila M, Hendrickson Carolyn M, Hite R Duncan, Hindenburg Alexander A, Hope Aluko A, Horowitz James M, Horvat Christopher M, Hudock Kristin, Hunt Beverley J, Husain Mansoor, Hyzy Robert C, Iyer Vivek N, Jacobson Jeffrey R, Jayakumar Devachandran, Keller Norma M, Khan Akram, Kim Yuri, Kindzelski Andrei L, King Andrew J, Knudson M Margaret, Kornblith Aaron E, Krishnan Vidya, Kutcher Matthew E, Laffan Michael A, Lamontagne Francois, Le Gal Grégoire, Leeper Christine M, Leifer Eric S, Lim George, Lima Felipe Gallego, Linstrum Kelsey, Litton Edward, Lopez-Sendon Jose, Lopez-Sendon Moreno Jose L, Lother Sylvain A, Malhotra Saurabh, Marcos Miguel, Saud Marinez Andréa, Marshall John C, Marten Nicole, Matthay Michael A, McAuley Daniel F, McDonald Emily G, McGlothlin Anna, McGuinness Shay P, Middeldorp Saskia, Montgomery Stephanie K, Moore Steven C, Morillo Guerrero Raquel, Mouncey Paul R, Murthy Srinivas, Nair Girish B, Nair Rahul, Nichol Alistair D, Nunez-Garcia Brenda, Pandey Ambarish, Park Pauline K, Parke Rachael L, Parker Jane C, Parnia Sam, Paul Jonathan D, Pérez González Yessica S, Pompilio Mauricio, Prekker Matthew E, Quigley John G, Rost Natalia S, Rowan Kathryn, Santos Fernanda O, Santos Marlene, Olombrada Santos Mayler, Satterwhite Lewis, Saunders Christina T, Schutgens Roger E G, Seymour Christopher W, Siegal Deborah M, Silva Delcio G, Shankar-Hari Manu, Sheehan John P, Singhal Aneesh B, Solvason Dayna, Stanworth Simon J, Tritschler Tobias, Turner Anne M, van Bentum-Puijk Wilma, van de Veerdonk Frank L, van Diepen Sean, Vazquez-Grande Gloria, Wahid Lana, Wareham Vanessa, Wells Bryan J, Widmer R Jay, Wilson Jennifer G, Yuriditsky Eugene, Zampieri Fernando G, Angus Derek C, McArthur Colin J, Webb Steven A, Farkouh Michael E, Hochman Judith S, Zarychanski Ryan

Сравнительное исследованиеСтатьяМногоцентровое исследованиеPragmatic Clinical TrialРандомизированное исследованиеПеревод в очереди

Аннотация

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. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Для цитирования: ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Lawler Patrick R, Goligher Ewan C, Berger Jeffrey S, Neal Matthew D, McVerry Bryan J, Nicolau Jose C, Gong Michelle N, Carrier Marc, Rosenson Robert S, Reynolds Harmony R, Turgeon Alexis F, Escobedo Jorge, Huang David T, Bradbury Charlotte A, Houston Brett L, Kornblith Lucy Z, Kumar Anand, Kahn Susan R, Cushman Mary, McQuilten Zoe, Slutsky Arthur S, Kim Keri S, Gordon Anthony C, Kirwan Bridget-Anne, Brooks Maria M, Higgins Alisa M, Lewis Roger J, Lorenzi Elizabeth, Berry Scott M, Berry Lindsay R, Aday Aaron W, Al-Beidh Farah, Annane Djillali, Arabi Yaseen M, Aryal Diptesh, Baumann Kreuziger Lisa, Beane Abi, Bhimani Zahra, Bihari Shailesh, Billett Henny H, Bond Lindsay, Bonten Marc, Brunkhorst Frank, Buxton Meredith, Buzgau Adrian, Castellucci Lana A, Chekuri Sweta, Chen Jen-Ting, Cheng Allen C, Chkhikvadze Tamta, Coiffard Benjamin, Costantini Todd W, de Brouwer Sophie, Derde Lennie P G, Detry Michelle A, Duggal Abhijit, Džavík Vladimír, Effron Mark B, Estcourt Lise J, Everett Brendan M, Fergusson Dean A, Fitzgerald Mark, Fowler Robert A, Galanaud Jean P, Galen Benjamin T, Gandotra Sheetal, García-Madrona Sebastian, Girard Timothy D, Godoy Lucas C, Goodman Andrew L, Goossens Herman, Green Cameron, Greenstein Yonatan Y, Gross Peter L, Hamburg Naomi M, Haniffa Rashan, Hanna George, Hanna Nicholas, Hegde Sheila M, Hendrickson Carolyn M, Hite R Duncan, Hindenburg Alexander A, Hope Aluko A, Horowitz James M, Horvat Christopher M, Hudock Kristin, Hunt Beverley J, Husain Mansoor, Hyzy Robert C, Iyer Vivek N, Jacobson Jeffrey R, Jayakumar Devachandran, Keller Norma M, Khan Akram, Kim Yuri, Kindzelski Andrei L, King Andrew J, Knudson M Margaret, Kornblith Aaron E, Krishnan Vidya, Kutcher Matthew E, Laffan Michael A, Lamontagne Francois, Le Gal Grégoire, Leeper Christine M, Leifer Eric S, Lim George, Lima Felipe Gallego, Linstrum Kelsey, Litton Edward, Lopez-Sendon Jose, Lopez-Sendon Moreno Jose L, Lother Sylvain A, Malhotra Saurabh, Marcos Miguel, Saud Marinez Andréa, Marshall John C, Marten Nicole, Matthay Michael A, McAuley Daniel F, McDonald Emily G, McGlothlin Anna, McGuinness Shay P, Middeldorp Saskia, Montgomery Stephanie K, Moore Steven C, Morillo Guerrero Raquel, Mouncey Paul R, Murthy Srinivas, Nair Girish B, Nair Rahul, Nichol Alistair D, Nunez-Garcia Brenda, Pandey Ambarish, Park Pauline K, Parke Rachael L, Parker Jane C, Parnia Sam, Paul Jonathan D, Pérez González Yessica S, Pompilio Mauricio, Prekker Matthew E, Quigley John G, Rost Natalia S, Rowan Kathryn, Santos Fernanda O, Santos Marlene, Olombrada Santos Mayler, Satterwhite Lewis, Saunders Christina T, Schutgens Roger E G, Seymour Christopher W, Siegal Deborah M, Silva Delcio G, Shankar-Hari Manu, Sheehan John P, Singhal Aneesh B, Solvason Dayna, Stanworth Simon J, Tritschler Tobias, Turner Anne M, van Bentum-Puijk Wilma, van de Veerdonk Frank L, van Diepen Sean, Vazquez-Grande Gloria, Wahid Lana, Wareham Vanessa, Wells Bryan J, Widmer R Jay, Wilson Jennifer G, Yuriditsky Eugene, Zampieri Fernando G, Angus Derek C, McArthur Colin J, Webb Steven A, Farkouh Michael E, Hochman Judith S, Zarychanski Ryan. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.. The New England journal of medicine. 2021. DOI: 10.1056/nejmoa2105911.

Предметные рубрики MeSH

Adult Aged Anticoagulants COVID-19 Female Hemorrhage Heparin Heparin, Low-Molecular-Weight Hospital Mortality Humans Male Middle Aged Survival Analysis Thrombosis COVID-19 Drug Treatment

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