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Atorvastatin Versus Placebo in Icu Patients With Covid-19: Ninety-Day Results of the Inspiration-S Trial Publisher Pubmed



Talasaz AH1, 2 ; Sadeghipour P3, 4, 5 ; Bakhshandeh H3, 4 ; Sharifkashani B6, 7 ; Rashidi F8 ; Beigmohammadi MT9 ; Moghadam KG10 ; Rezaian S11 ; Dabbagh A12 ; Sezavar SH13 ; Farrokhpour M14 ; Abedini A15 ; Aliannejad R16, 17 ; Riahi T18 Show All Authors
Authors
  1. Talasaz AH1, 2
  2. Sadeghipour P3, 4, 5
  3. Bakhshandeh H3, 4
  4. Sharifkashani B6, 7
  5. Rashidi F8
  6. Beigmohammadi MT9
  7. Moghadam KG10
  8. Rezaian S11
  9. Dabbagh A12
  10. Sezavar SH13
  11. Farrokhpour M14
  12. Abedini A15
  13. Aliannejad R16, 17
  14. Riahi T18
  15. Yadollahzadeh M14
  16. Lookzadeh S15
  17. Rezaeifar P8
  18. Matin S8
  19. Tahamtan O8
  20. Mohammadi K19
  21. Zoghi E19
  22. Rahmani H19
  23. Hosseini SH19
  24. Mousavian SM18
  25. Abri H14
  26. Sadeghipour P3, 4, 5
  27. Baghizadeh E3
  28. Rafiee F3
  29. Jamalkhani S20, 21
  30. Amin A3
  31. Mohebbi B5
  32. Parhizgar SE3
  33. Soleimanzadeh M12
  34. Aghakouchakzadeh M19
  35. Eslami V22
  36. Payandemehr P23
  37. Khalili H21
  38. Talakoob H24
  39. Tojari T25
  40. Shafaghi S7
  41. Tabrizi S18
  42. Kakavand H19
  43. Kashefizadeh A26
  44. Najafi A22
  45. Jimenez D27, 28, 29
  46. Gupta A30, 31
  47. Madhavan MV32, 33
  48. Sethi SS32, 33
  49. Parikh SA32, 33
  50. Monreal M34
  51. Hadavand N3
  52. Hajighasemi A1
  53. Ansarin K8
  54. Maleki M3
  55. Sadeghian S1
  56. Barco S35, 36
  57. Siegerink B37
  58. Spatz ES38, 39
  59. Piazza G40, 41
  60. Kirtane AJ40, 41
  61. Van Tassell BW2
  62. Lip GYH42, 43
  63. Klok FA44
  64. Goldhaber SZ40, 41
  65. Stone GW32, 45
  66. Krumholz HM30, 39, 46
  67. Bikdeli B32, 38, 40, 41
Show Affiliations
Authors Affiliations
  1. 1. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, VA, United States
  3. 3. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Tobacoo Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Department of Cardiology, Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
  8. 8. Tuberclosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  9. 9. Department of Intensive Care, Tehran University of Medical Sciences, Imam Khomeini Hospital Complex, Tehran, Iran
  10. 10. Department of Internal Medicine, School of Medicine, Shariati Hospital, Tehran, Iran
  11. 11. Department of Internal Medicine, Alborz University of Medicine Science, Karaj, Iran
  12. 12. Department of Anesthesiology, School of Medicine Anesthesiology Research Center Shahid Modarres Hospital, Shahid Beheshti 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. Department of Internal Medicine, Iran University of Medical Sciences, Firouzgar Hospital, Tehran, Iran
  15. 15. Chronic Respiratory Disease Research Center, Shahid Beheshti University of Medical Sciences, Masih Daneshvari Hospital, Tehran, Iran
  16. 16. Department of Pulmonary and Critical Care, School of Medicine, Shariati Hospital, Tehran, Iran
  17. 17. Advanced Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran
  18. 18. Department of Internal Medicine, Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  19. 19. Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  20. 20. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
  21. 21. Department of Pharmacotherapy, Tehran University of Medical Sciences, Imam Khomeini Hospital Complex, Tehran, Iran
  22. 22. Department of Emergency Medicine, Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  23. 23. Department of Emergency Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  24. 24. Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
  25. 25. Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
  26. 26. Department of Internal Medicine, Shahid Dr. Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  27. 27. Respiratory Department, Hospital Ramon y Cajal (IRYCIS), Madrid, Spain
  28. 28. Medicine Department, Universidad de Alcala (IRYCIS), Madrid, Spain
  29. 29. CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain
  30. 30. Yale/YNHH Center for Outcomes Research and Evaluation (CORE), New Haven, CT, United States
  31. 31. Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, United States
  32. 32. Cardiovascular Research Foundation (CRF), New York, NY, United States
  33. 33. Division of Cardiology, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY, United States
  34. 34. Catedra de Enfermedad Tromboembolica, Universidad Catolica de Murcia, Murcia, Spain
  35. 35. Department of Angiology, University Hospital Zurich, Zurich, Switzerland
  36. 36. Center for Thrombosis and Hemostasis, Johannes Gutenberg University Mainz, Mainz, Germany
  37. 37. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
  38. 38. Yale/YNHH Center for Outcomes Research and Evaluation, New Haven, CT, United States
  39. 39. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States
  40. 40. Cardiovascular Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  41. 41. Thrombosis Research Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  42. 42. Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart, Chest Hospital, Liverpool, United Kingdom
  43. 43. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  44. 44. Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Centre, Leiden, Netherlands
  45. 45. Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  46. 46. Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, United States

Source: Thrombosis and Haemostasis Published:2023


Abstract

Background In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. Methods This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. Results In the primary analysis, 587 patients were included (age: 57 [Q1–Q3: 45–68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60–1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42–0.86, pinteraction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41–1.01, p = 0.05). Conclusion Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508). © 2023. Thieme. All rights reserved.
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