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Intermediate-Dose Versus Standard-Dose Prophylactic Anticoagulation in Patients With Covid-19 Admitted to the Intensive Care Unit: 90-Day Results From the Inspiration Randomized Trial Publisher Pubmed



Bikdeli B1, 2, 3 ; Talasaz AH4 ; Rashidi F5 ; Bakhshandeh H6, 7 ; Rafiee F7 ; Rezaeifar P5 ; Baghizadeh E7 ; Matin S5 ; Jamalkhani S8 ; Tahamtan O5 ; Sharifkashani B9, 10 ; Beigmohammadi MT11 ; Farrokhpour M12 ; Sezavar SH13 Show All Authors
Authors
  1. Bikdeli B1, 2, 3
  2. Talasaz AH4
  3. Rashidi F5
  4. Bakhshandeh H6, 7
  5. Rafiee F7
  6. Rezaeifar P5
  7. Baghizadeh E7
  8. Matin S5
  9. Jamalkhani S8
  10. Tahamtan O5
  11. Sharifkashani B9, 10
  12. Beigmohammadi MT11
  13. Farrokhpour M12
  14. Sezavar SH13
  15. Payandemehr P14
  16. Dabbagh A15
  17. Moghadam KG16
  18. Khalili H17
  19. Yadollahzadeh M12
  20. Riahi T18
  21. Abedini A19
  22. Lookzadeh S19
  23. Rahmani H20
  24. Zoghi E21
  25. Mohammadi K21
  26. Sadeghipour P12
  27. Abri H12
  28. Tabrizi S18
  29. Mousavian SM18
  30. Shahmirzaei S14
  31. Amin A7
  32. Mohebbi B22
  33. Parhizgar SE7
  34. Aliannejad R23, 24
  35. Eslami V25
  36. Kashefizadeh A26
  37. Dobesh PP27
  38. Kakavand H21
  39. Hosseini SH21
  40. Shafaghi S10
  41. Ghazi SF11
  42. Najafi A14
  43. Jimenez D28, 29, 30
  44. Gupta A2, 3, 31
  45. Madhavan MV3, 31
  46. Sethi SS3, 31
  47. Parikh SA3, 31
  48. Monreal M32, 33
  49. Hadavand N7
  50. Hajighasemi A4
  51. Maleki M7
  52. Sadeghian S4
  53. Piazza G1
  54. Kirtane AJ3, 31
  55. Van Tassell BW34, 35
  56. Stone GW3, 36
  57. Lip GYH37, 38
  58. Krumholz HM2, 39, 40
  59. Goldhaber SZ1
  60. Sadeghipour P12
Show Affiliations
Authors Affiliations
  1. 1. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
  2. 2. Yale/YNHH Center for Outcomes Research and Evaluation, New Haven, CT, United States
  3. 3. Cardiovascular Research Foundation, New York, NY, United States
  4. 4. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
  7. 7. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
  9. 9. Tobacoo Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  10. 10. Department of Cardiology, Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  11. 11. Anesthesiology and Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Department of Internal Medicine, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran
  13. 13. Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
  14. 14. Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  15. 15. Department of Anesthesiology, School of Medicine Anesthesiology Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  16. 16. Department of Internal Medicine, School of Medicine, Shariati Hospital, Tehran, Iran
  17. 17. Department of Pharmacotherapy, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  18. 18. Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  19. 19. Chronic Respiratory Disease Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  20. 20. Department of Pharmacotherapy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
  21. 21. School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  22. 22. Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
  23. 23. Department of Pulmonary and Critical Care, School of Medicine, Shariati Hospital, Tehran, Iran
  24. 24. Advanced Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran
  25. 25. Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  26. 26. Shahid Dr. Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  27. 27. College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, United States
  28. 28. Respiratory Department, Hospital Ramon y Cajal, Madrid, Spain
  29. 29. Medicine Department, Universidad de Alcala, Madrid, Spain
  30. 30. CIBER Enfermedades Respiratorias, Madrid, Spain
  31. 31. Division of Cardiology, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY, United States
  32. 32. Department of Internal Medicine, Hospital Germans Trias i Pujol, Barcelona, Badalona, Spain
  33. 33. Universidad Catolica de Murcia, Murcia, Spain
  34. 34. Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, United States
  35. 35. Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, United States
  36. 36. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  37. 37. Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
  38. 38. Aalborg University, Aalborg, Denmark
  39. 39. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States
  40. 40. Department of Health Policy and Administration, Yale School of Public Health, New Haven, CT, United States

Source: Thrombosis and Haemostasis Published:2021


Abstract

Background  Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods  This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results  Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). Conclusion  Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up. © 2021. Thieme. All rights reserved.
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