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Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care UnitThe INSPIRATION Randomized Clinical Trial

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What are the effects of intermediate-dose compared with standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit (ICU)?

Findings  In this randomized clinical trial that included 562 patients with COVID-19 admitted to the ICU, the primary outcome (a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days) occurred in 45.7% of patients in the intermediate-dose prophylactic anticoagulation group and 44.1% of patients in the standard-dose prophylactic anticoagulation group, a difference that was not statistically significant (odds ratio, 1.06).

Meaning  The results do not support routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients with COVID-19 admitted to the ICU.

Abstract

Importance  Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis.

Objective  To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU).

Design, Setting, and Participants  Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020.

Interventions  Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up.

Main Outcomes and Measures  The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated.

Results  Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, −6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, −∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01).

Conclusions and Relevance  Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19.

Trial Registration  ClinicalTrials.gov Identifier: NCT04486508

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Article Information

Corresponding Authors: Parham Sadeghipour, MD, Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Vali-Asr Ave, Niyayesh Blvd, Tehran 1996911101, Iran (psadeghipour@hotmail.com); Behnood Bikdeli, MD, MS, Cardiovascular Medicine Division, Brigham and Women’s Hospital, 75 Francis St, Shapiro 5, Ste 5156, Boston, MA 02115 (bbikdeli@bwh.harvard.edu; behnood.bikdeli@yale.edu).

Accepted for Publication: March 4, 2021.

Published Online: March 18, 2021. doi:10.1001/jama.2021.4152

Authors/INSPIRATION Investigators: Parham Sadeghipour, MD; Azita H. Talasaz, PharmD; Farid Rashidi, MD; Babak Sharif-Kashani, MD; Mohammad Taghi Beigmohammadi, MD; Mohsen Farrokhpour, MD; Seyed Hashem Sezavar, MD; Pooya Payandemehr, MD; Ali Dabbagh, MD; Keivan Gohari Moghadam, MD; Sepehr Jamalkhani, MD (’23); Hossein Khalili, PharmD; Mahdi Yadollahzadeh, MD; Taghi Riahi, MD; Parisa Rezaeifar, MD; Ouria Tahamtan, MD; Samira Matin, MD; Atefeh Abedini, MD; Somayeh Lookzadeh, MD; Hamid Rahmani, PharmD; Elnaz Zoghi, PharmD; Keyhan Mohammadi, PharmD; Pardis Sadeghipour, MD; Homa Abri, MD; Sanaz Tabrizi, MD; Seyed Masoud Mousavian, MD; Shaghayegh Shahmirzaei, MD; Hooman Bakhshandeh, MD, PhD; Ahmad Amin, MD; Farnaz Rafiee, MD; Elahe Baghizadeh, MD; Bahram Mohebbi, MD; Seyed Ehsan Parhizgar, MD; Rasoul Aliannejad, MD; Vahid Eslami, MD; Alireza Kashefizadeh, MD; Hessam Kakavand, PharmD; Seyed Hossein Hosseini, PharmD; Shadi Shafaghi, MD; Samrand Fattah Ghazi, MD; Atabak Najafi, MD; David Jimenez, MD, PhD; Aakriti Gupta, MD, MS; Mahesh V. Madhavan, MD; Sanjum S. Sethi, MD, MPH; Sahil A. Parikh, MD; Manuel Monreal, MD; Naser Hadavand, PharmD; Alireza Hajighasemi, PharmD; Majid Maleki, MD; Saeed Sadeghian, MD; Gregory Piazza, MD, MS; Ajay J. Kirtane, MD, SM; Benjamin W. Van Tassell, PharmD; Paul P. Dobesh, PharmD; Gregg W. Stone, MD; Gregory Y. H. Lip, MD; Harlan M. Krumholz, MD, SM; Samuel Z. Goldhaber, MD; Behnood Bikdeli, MD, MS.

Affiliations of Authors/INSPIRATION Investigators: Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran (Parham Sadeghipour, Mohebbi); Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran (Parham Sadeghipour, Bakhshandeh); Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran (Talasaz, Hajighasemi, Sadeghian); Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (Rashidi, Rezaeifar, Tahamtan, Matin); Tobacoo Prevention and control Research center, National Research institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran (Sharif-Kashani); Lung Transplantation Research Center, Department of Cardiology, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran (Sharif-Kashani, Shafaghi); Anesthesiology and Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran (Beigmohammadi, Ghazi); Firouzgar hospital, Department of internal medicine, Iran University of Medical Sciences, Tehran, Iran (Farrokhpour, Yadollahzadeh, Pardis Sadeghipour, Abri); Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran (Sezavar); Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran (Payandemehr, Shahmirzaei, Najafi); Department of Anesthesiology, School of Medicine Anesthesiology Research Center Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Dabbagh); School of Medicine, Department of Internal Medicine, Shariati Hospital, Tehran, Iran (Moghadam); Student Research Committee, Iran University of Medical Sciences, Tehran, Iran (Jamalkhani); Department of Pharmacotherapy, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran (Khalili); Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran (Riahi, Tabrizi, Mousavian); Chronic Respiratory Disease Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Abedini, Lookzadeh); Department of Pharmacotherapy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran (Rahmani); School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran (Zoghi, Mohammadi, Kakavand, Hosseini); Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran (Bakhshandeh, Amin, Rafiee, Baghizadeh, Parhizgar, Hadavand, Maleki); School of Medicine, Department of Pulmonary and Critical Care, Shariati Hospital, Tehran, Iran (Aliannejad); Advanced Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran (Aliannejad); Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Eslami); Shahid Dr Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Kashefizadeh); Respiratory Department, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (Jimenez); Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain (Jimenez); CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain (Jimenez); Cardiovascular Research Foundation (CRF), New York, New York (Gupta, Madhavan, Sethi, Parikh, Kirtane, Stone, Bikdeli); Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York (Gupta, Madhavan, Sethi, Parikh, Kirtane); Yale/YNHH Center for Outcomes Research & Evaluation, New Haven, Connecticut (Gupta, Krumholz, Bikdeli); Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Universidad Católica de Murcia, Murcia, Spain (Monreal); Cardiovascular Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts (Piazza, Goldhaber, Bikdeli); School of Pharmacy, Department of Pharmacotherapy and Outcome Science, Virginia Commonwealth University, Richmond, Virginia (Van Tassell); School of Pharmacy, Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia (Van Tassell); College of Pharmacy, University of Nebraska Medical Center, Omaha (Dobesh); The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York (Stone); Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom (Lip); Aalborg University, Aalborg, Denmark (Lip); Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (Krumholz); Department of Health Policy and Administration, Yale School of Public Health, New Haven, Connecticut (Krumholz).

Author Contributions: Dr Sadeghipour had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Parham Sadeghipour, Talasaz, Rashidi, Sharif-Kashani, Beigmohammadi, Sezavar, Payandemehr, Dabbagh, Gohari Moghadam, Riahi, Abedini, Mohebbi, Kakavand, Fattah Ghazi, Najafi, Jimenez, Sethi, Monreal, Hajighasemi, Sadeghian, Piazza, Kirtane, Dobesh, Bikdeli.

Acquisition, analysis, or interpretation of data: Parham Sadeghipour, Talasaz, Sharif-Kashani, Beigmohammadi, Farrokhpour, Payandemehr, Dabbagh, Jamalkhani, Khalili, Yadollahzadeh, Rezaeifar, Tahamtan, Matin, Lookzadeh, Rahmani, Zoghi, Mohammadi, Pardis Sadeghipour, Abri, Tabrizi, Mousavian, Shahmirzaei, Bakhshandeh, Amin, Rafiee, Baghizadeh, Mohebbi, Parhizgar, Aliannejad, Eslami, Kashefizadeh, Hosseini, Shafaghi, Jimenez, Gupta, Madhavan, Sethi, Parikh, Hadavand, Maleki, Piazza, Van Tassell, Stone, Lip, Krumholz, Goldhaber, Bikdeli.

Drafting of the manuscript: Parham Sadeghipour, Talasaz, Sharif-Kashani, Farrokhpour, Payandemehr, Jamalkhani, Khalili, Yadollahzadeh, Riahi, Rezaeifar, Tahamtan, Matin, Lookzadeh, Pardis Sadeghipour, Abri, Tabrizi, Mousavian, Shahmirzaei, Rafiee, Baghizadeh, Mohebbi, Parhizgar, Eslami, Kashefizadeh, Hosseini, Shafaghi, Fattah Ghazi, Najafi, Bikdeli.

Critical revision of the manuscript for important intellectual content: Parham Sadeghipour, Talasaz, Rashidi, Beigmohammadi, Sezavar, Payandemehr, Dabbagh, Gohari Moghadam, Abedini, Rahmani, Zoghi, Mohammadi, Bakhshandeh, Amin, Mohebbi, Aliannejad, Kakavand, Najafi, Jimenez, Gupta, Madhavan, Sethi, Parikh, Monreal, Hadavand, Hajighasemi, Maleki, Sadeghian, Piazza, Kirtane, Van Tassell, Dobesh, Stone, Lip, Krumholz, Goldhaber, Bikdeli.

Statistical analysis: Parham Sadeghipour, Bakhshandeh, Mohebbi, Jimenez.

Obtained funding: Parham Sadeghipour, Abedini, Najafi.

Administrative, technical, or material support: Parham Sadeghipour, Talasaz, Beigmohammadi, Payandemehr, Gohari Moghadam, Khalili, Abedini, Rahmani, Zoghi, Mohammadi, Amin, Mohebbi, Parhizgar, Aliannejad, Kakavand, Fattah Ghazi, Najafi, Sethi, Hadavand, Hajighasemi, Maleki, Sadeghian, Piazza, Bikdeli.

Supervision: Parham Sadeghipour, Talasaz, Rashidi, Sharif-Kashani, Beigmohammadi, Payandemehr, Gohari Moghadam, Riahi, Mohebbi, Gupta, Monreal, Piazza, Van Tassell, Dobesh, Goldhaber, Bikdeli.

Other - monitoring of the study progress, supporting patient recruitment, data clarifications, and data entry: Sharif-Kashani, Farrokhpour, Sezavar, Jamalkhani, Yadollahzadeh, Rezaeifar, Tahamtan, Matin, Lookzadeh, Pardis Sadeghipour, Abri, Tabrizi, Mousavian, Shahmirzaei, Eslami, Kashefizadeh, Hosseini, Shafaghi.

Conflict of Interest Disclosures: Dr Jimenez reported receiving personal fees from Bristol Myers Squibb, Daiichi-Sankyo, Bayer, Pfizer, Rovi, and Leo-Pharma and grants from Sanofi outside the submitted work. Dr Gupta reported receiving consulting fees from Edwards Lifesciences, Arnold Porter Law Firm, and Ben C. Martin Law Firm and equity from Heartbeat Health Inc outside the submitted work. Dr Madhavan reported receiving an institutional research grant to Columbia University Irving Medical Center (T32 HL007854) from the National Institutes of Health/National Heart, Lung, and Blood Institute during the conduct of the study. Dr Sethi reported receiving personal fees from Janssen and Chiesi and grants from the American Heart Association outside the submitted work. Dr Parikh reported receiving grants from Abbott Vascular, Boston Scientific, Surmodics, and TriReme Medical; nonfinancial support from Cordis, Medtronic, Philips, and Cardiovascular Systems Inc; and personal fees from Terumo, Abiomed, Inari, and Penumbra outside the submitted work. Dr Monreal reported receiving grants from Sanofi outside the submitted work. Dr Piazza reported receiving grants from Bristol Myers Squibb/Pfizer, Janssen, Portola, Boston Scientific, and Bayer and serving on a data and safety monitoring board for Prairie Education and Research Cooperative outside the submitted work. Dr Kirtane reported receiving institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems Inc, CathWorks, Siemens, Philips, and ReCor Medical, including fees paid to Columbia University and/or the Cardiovascular Research Foundation for speaking engagements and/or consulting; consulting fees from Neurotronic; and travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems Inc, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr Dobesh reported receiving personal fees from the Pfizer/Bristol Myers Squibb Alliance and Janssen Pharmaceuticals outside the submitted work. Dr Stone reported receiving personal fees from Terumo, Cook, TherOx, Reva, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Matrizyme, Miracor Neovasc, V-wave, Abiomed, MAIA Pharmaceuticals, Shockwave, Vectorious, Cardiomech , and Elucid Bio; equity/equity options from Applied Therapeutics, MedFocus, Biostar, Aria, Cagent, Cardiac Success; personal fees and equity/equity options from Spectrawave, Valfix, Ancora; and personal fees, equity/equity options, and honorarium from Orchestra Biomed, and outside the submitted work. Dr Lip reported being a consultant and speaker for Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo outside the submitted work. Dr Krumholz reported receiving personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, Siegfried & Jensen Law Firm, Arnold & Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases, Beijing; being the cofounder of HugoHealth, a personal health information platform, and Refactor Health, an enterprise health care artificial intelligence–augmented data management company; receiving contracts from the Centers for Medicare & Medicaid Services, through Yale New Haven Hospital, to develop and maintain measures of hospital performance; and receiving grants from Medtronic, the US Food and Drug Administration, Johnson & Johnson, and the Shenzhen Center for Health Information outside the submitted work. Dr Goldhaber reported receiving grants from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Boston Scientific, Janssen, the National Heart, Lung, and Blood Institute, and Pfizer and personal fees from Agile, Bayer, Boehringer-Ingelheim, and Pfizer outside the submitted work. Dr Bikdeli reported being a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of inferior vena cava filters. No other disclosures were reported.

Funding/Support: The study was funded by the Rajaie Cardiovascular Medical and Research Center. Some study authors, including the lead author, are affiliated with the Rajaie Cardiovascular Medical and Research Center. Enoxaparin was provided through Alborz Darou, Pooyesh Darou, and Caspian Pharmaceuticals companies, and atorvastatin and matching placebo was provided by Sobhan Darou. None of these companies were study sponsors.

Role of the Funder/Sponsor: Some study authors are affiliated with the study funder (Rajaie Cardiovascular and Medical Research Center). Neither the funder, nor the companies who donated the study drugs (Alborz Darou, Pooyesh Darou and Caspian Pharmaceuticals) had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: A list of the INSPIRATION collaborators appears in Supplement 4.

Data Sharing Statement: See Supplement 5.

Additional Contributions: The authors would like to thank the members of the data and safety monitoring board, Saeideh Mazloomzadeh, MD, PhD; Shiva Khaleghparast, PhD; Behshid Ghadrdoost, PhD; Mostafa Mousavizadeh, MD; and Mohammad Reza Baay, MD (Rajaie Cardiovascular, Medical and Research Center). The authors would also like to thank Feridoun Noohi, MD (Rajaie Cardiovascular, Medical and Research Center), for his support for performing this study, Hamidreza Sharifnia, MD; Arezoo Ahmadi, MD (Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran); Sasan Tavana, MD; Nasser Malekpour Alamdari, MD; Mohammad Fathi, MD; Mahshid Soleimanzadeh, MD (Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran); Mostafa Mohammadi, MD (Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran); and Navid Davoody, MD (Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran), for their kind support for patient recruitment and Maryam Zarinsadaf, Sara Tayyebi, MS; Fahimeh Farrokhzadeh, MS; Faeze Nezamabadi, MS; and Esmaeil Soomari, MS (Rajaie Cardiovascular, Medical and Research Center), for their support and contribution to the INSPIRATION study.

References
1.
Ackermann  M , Verleden  SE , Kuehnel  M ,  et al.  Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19.   N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432PubMedGoogle ScholarCrossref
2.
Wichmann  D , Sperhake  JP , Lütgehetmann  M ,  et al.  Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study.   Ann Intern Med. 2020;173(4):268-277. doi:10.7326/M20-2003PubMedGoogle ScholarCrossref
3.
Libby  P , Lüscher  T .  COVID-19 is, in the end, an endothelial disease.   Eur Heart J. 2020;41(32):3038-3044. doi:10.1093/eurheartj/ehaa623PubMedGoogle ScholarCrossref
4.
Bikdeli  B , Madhavan  MV , Jimenez  D ,  et al; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function.  COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: jacc state-of-the-art review.   J Am Coll Cardiol. 2020;75(23):2950-2973. doi:10.1016/j.jacc.2020.04.031PubMedGoogle ScholarCrossref
5.
Bilaloglu  S , Aphinyanaphongs  Y , Jones  S , Iturrate  E , Hochman  J , Berger  JS .  Thrombosis in hospitalized patients with COVID-19 in a New York City health system.   JAMA. 2020;324(8):799-801. doi:10.1001/jama.2020.13372PubMedGoogle ScholarCrossref
6.
Jiménez  D , García-Sanchez  A , Rali  P ,  et al.  Incidence of venous thromboembolism and bleeding among hospitalized patients with COVID-19: a systematic review and meta-analysis.   Chest. 2021;159(3):1182-1196. doi:10.1016/j.chest.2020.11.005PubMedGoogle ScholarCrossref
7.
Bikdeli  B , Madhavan  MV , Gupta  A ,  et al; Global COVID-19 Thrombosis Collaborative Group.  Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research.   Thromb Haemost. 2020;120(7):1004-1024. doi:10.1055/s-0040-1713152PubMedGoogle ScholarCrossref
8.
Paranjpe  I , Fuster  V , Lala  A ,  et al.  Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19.   J Am Coll Cardiol. 2020;76(1):122-124. doi:10.1016/j.jacc.2020.05.001PubMedGoogle ScholarCrossref
9.
Al-Samkari  H , Gupta  S , Karp Leaf  R ,  et al  Thrombosis, bleeding, and the effect of anticoagulation on survival in critically ill patients with COVID-19 in the United States.   Res Pract Thromb Haemost. 2020;4.Google Scholar
10.
Lemos  ACB , do Espírito Santo  DA , Salvetti  MC ,  et al.  Therapeutic versus prophylactic anticoagulation for severe COVID-19: a randomized phase II clinical trial (HESACOVID).   Thromb Res. 2020;196:359-366. doi:10.1016/j.thromres.2020.09.026PubMedGoogle ScholarCrossref
11.
Bikdeli  B .  Anticoagulation in COVID-19: randomized trials should set the balance between excitement and evidence.   Thromb Res. 2020;196:638-640. doi:10.1016/j.thromres.2020.09.033PubMedGoogle ScholarCrossref
12.
Barnes  GD , Burnett  A , Allen  A ,  et al.  Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.   J Thromb Thrombolysis. 2020;50(1):72-81. doi:10.1007/s11239-020-02138-zPubMedGoogle ScholarCrossref
13.
Moores  LK , Tritschler  T , Brosnahan  S ,  et al.  Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report.   Chest. 2020;158(3):1143-1163. doi:10.1016/j.chest.2020.05.559PubMedGoogle ScholarCrossref
14.
Ramacciotti  E , Macedo  AS , Biagioni  RB ,  et al.  Evidence-based practical guidance for the antithrombotic management in patients with coronavirus disease (COVID-19) in 2020.   Clin Appl Thromb Hemost. 2020;26:1076029620936350. doi:10.1177/1076029620936350PubMedGoogle Scholar
15.
Cuker  A , Tseng  EK , Nieuwlaat  R ,  et al.  American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19.   Blood Adv. 2021;5(3):872-888. doi:10.1182/bloodadvances.2020003763PubMedGoogle ScholarCrossref
16.
Bikdeli  B , Talasaz  AH , Rashidi  F ,  et al.  Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: rationale and design of the INSPIRATION/INSPIRATION-S studies.   Thromb Res. 2020;196:382-394. doi:10.1016/j.thromres.2020.09.027PubMedGoogle ScholarCrossref
17.
Mehran  R , Rao  SV , Bhatt  DL ,  et al.  Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium.   Circulation. 2011;123(23):2736-2747. doi:10.1161/CIRCULATIONAHA.110.009449PubMedGoogle ScholarCrossref
18.
Cook  D , Meade  M , Guyatt  G ,  et al; PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group.  Dalteparin versus unfractionated heparin in critically ill patients.   N Engl J Med. 2011;364(14):1305-1314. doi:10.1056/NEJMoa1014475PubMedGoogle ScholarCrossref
19.
Eck  RJ , Bult  W , Wetterslev  J ,  et al.  Intermediate dose low-molecular-weight heparin for thrombosis prophylaxis: systematic review with meta-analysis and trial sequential analysis.   Semin Thromb Hemost. 2019;45(8):810-824. doi:10.1055/s-0039-1696965PubMedGoogle ScholarCrossref
20.
Connors  JM , Levy  JH .  COVID-19 and its implications for thrombosis and anticoagulation.   Blood. 2020;135(23):2033-2040. doi:10.1182/blood.2020006000PubMedGoogle ScholarCrossref
21.
Levi  M , Thachil  J , Iba  T , Levy  JH .  Coagulation abnormalities and thrombosis in patients with COVID-19.   Lancet Haematol. 2020;7(6):e438-e440. doi:10.1016/S2352-3026(20)30145-9PubMedGoogle ScholarCrossref
22.
Piazza  G , Morrow  DA .  Diagnosis, management, and pathophysiology of arterial and venous thrombosis in COVID-19.   JAMA. 2020;324(24):2548-2549. doi:10.1001/jama.2020.23422PubMedGoogle ScholarCrossref
23.
Llitjos  JF , Leclerc  M , Chochois  C ,  et al.  High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.   J Thromb Haemost. 2020;18(7):1743-1746. doi:10.1111/jth.14869PubMedGoogle ScholarCrossref
24.
Al-Samkari  H , Karp Leaf  RS , Dzik  WH ,  et al.  COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection.   Blood. 2020;136(4):489-500. doi:10.1182/blood.2020006520PubMedGoogle ScholarCrossref
25.
Klok  FA , Kruip  MJHA , van der Meer  NJM ,  et al.  Incidence of thrombotic complications in critically ill ICU patients with COVID-19.   Thromb Res. 2020;191:145-147. doi:10.1016/j.thromres.2020.04.013PubMedGoogle ScholarCrossref
26.
Spyropoulos  AC .  The management of venous thromboembolism in hospitalized patients with COVID-19.   Blood Adv. 2020;4(16):4028. doi:10.1182/bloodadvances.2020002496PubMedGoogle ScholarCrossref
27.
NIH ACTIV trial of blood thinners pauses enrollment of critically ill COVID-19 patients. News release. National Institutes of Health. December 22, 2020. Accessed January 15, 2021. https://www.nih.gov/news-events/news-releases/nih-activ-trial-blood-thinners-pauses-enrollment-critically-ill-covid-19-patients
28.
Pannucci  CJ , Fleming  KI , Agarwal  J , Rockwell  WB , Prazak  AM , Momeni  A .  The impact of once- versus twice-daily enoxaparin prophylaxis on risk for venous thromboembolism and clinically relevant bleeding.   Plast Reconstr Surg. 2018;142(1):239-249. doi:10.1097/PRS.0000000000004517PubMedGoogle ScholarCrossref
29.
Yamakawa  K , Umemura  Y , Murao  S , Hayakawa  M , Fujimi  S .  Optimal timing and early intervention with anticoagulant therapy for sepsis-induced disseminated intravascular coagulation.   Clin Appl Thromb Hemost. 2019;25:1076029619835055. doi:10.1177/1076029619835055PubMedGoogle Scholar
30.
Cummings  MJ , Baldwin  MR , Abrams  D ,  et al.  Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study.   Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2PubMedGoogle ScholarCrossref
31.
Grasselli  G , Zangrillo  A , Zanella  A ,  et al; COVID-19 Lombardy ICU Network.  Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.   JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394PubMedGoogle ScholarCrossref
32.
White  D , MacDonald  S , Bull  T ,  et al.  Heparin resistance in COVID-19 patients in the intensive care unit.   J Thromb Thrombolysis. 2020;50(2):287-291. doi:10.1007/s11239-020-02145-0PubMedGoogle ScholarCrossref
33.
Talasaz AH, Sadeghipour P, Kakavand H, et al.  Antithrombotic therapy in COVID-19: systematic summary of ongoing or completed randomized trials.   J Am Coll Cardiol. Published online March 16, 2021. doi:10.1016/j.jacc.2021.02.035Google Scholar
34.
Piazza  G , Campia  U , Hurwitz  S ,  et al.  Registry of arterial and venous thromboembolic complications in patients with COVID-19.   J Am Coll Cardiol. 2020;76(18):2060-2072. doi:10.1016/j.jacc.2020.08.070PubMedGoogle ScholarCrossref
35.
Hendren  NS , de Lemos  JA , Ayers  C ,  et al.  Association of body mass index and age with morbidity and mortality in patients hospitalized with COVID-19: results from the American Heart Association COVID-19 Cardiovascular Disease Registry.   Circulation. 2021;143(2):135-144. doi:10.1161/CIRCULATIONAHA.120.051936PubMedGoogle ScholarCrossref
36.
Horby  P , Lim  WS , Emberson  JR ,  et al; RECOVERY Collaborative Group.  Dexamethasone in hospitalized patients with Covid-19.   N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436PubMedGoogle ScholarCrossref
37.
Tomazini  BM , Maia  IS , Cavalcanti  AB ,  et al; COALITION COVID-19 Brazil III Investigators.  Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial.   JAMA. 2020;324(13):1307-1316. doi:10.1001/jama.2020.17021PubMedGoogle ScholarCrossref
38.
Sterne  JAC , Murthy  S , Diaz  JV ,  et al; WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.  Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.   JAMA. 2020;324(13):1330-1341. doi:10.1001/jama.2020.17023PubMedGoogle ScholarCrossref
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