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Randomized Controlled Trial
. 2023 Jul;123(7):723-733.
doi: 10.1055/a-2059-4844. Epub 2023 Mar 21.

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial

Azita H Talasaz  1   2 , Parham Sadeghipour  3   4   5 , Hooman Bakhshandeh  3   4 , Babak Sharif-Kashani  6   7 , Farid Rashidi  8 , Mohammad Taghi Beigmohammadi  9 , Keivan Gohari Moghadam  10 , Somaye Rezaian  11 , Ali Dabbagh  12 , Seyed Hashem Sezavar  13 , Mohsen Farrokhpour  14 , Atefeh Abedini  15 , Rasoul Aliannejad  16   17 , Taghi Riahi  18 , Mahdi Yadollahzadeh  14 , Somayeh Lookzadeh  15 , Parisa Rezaeifar  8 , Samira Matin  8 , Ouria Tahamtan  8 , Keyhan Mohammadi  19 , Elnaz Zoghi  19 , Hamid Rahmani  19 , Seyed Hossein Hosseini  19 , Seyed Masoud Mousavian  18 , Homa Abri  14 , Pardis Sadeghipour  14 , Elahe Baghizadeh  3 , Farnaz Rafiee  3 , Sepehr Jamalkhani  20   21 , Ahmad Amin  3 , Bahram Mohebbi  5 , Seyed Ehsan Parhizgar  3 , Mahshid Soleimanzadeh  12 , Maryam Aghakouchakzadeh  19 , Vahid Eslami  22 , Pooya Payandemehr  23 , Hossein Khalili  21 , Hamed Talakoob  24 , Taranom Tojari  25 , Shadi Shafaghi  7 , Sanaz Tabrizi  18 , Hessam Kakavand  19 , Alireza Kashefizadeh  26 , Atabak Najafi  22 , David Jimenez  27   28   29 , Aakriti Gupta  30   31 , Mahesh V Madhavan  32   33 , Sanjum S Sethi  32   33 , Sahil A Parikh  32   33 , Manuel Monreal  34 , Naser Hadavand  3 , Alireza Hajighasemi  1 , Khalil Ansarin  8 , Majid Maleki  3 , Saeed Sadeghian  1 , Stefano Barco  35   36 , Bob Siegerink  37 , Erica S Spatz  38   39 , Gregory Piazza  40   41 , Ajay J Kirtane  40   41 , Benjamin W Van Tassell  2 , Gregory Y H Lip  42   43 , Frederikus A Klok  44 , Samuel Z Goldhaber  40   41 , Gregg W Stone  32   45 , Harlan M Krumholz  30   39   46 , Behnood Bikdeli  32   38   40   41
Affiliations
Randomized Controlled Trial

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial

Azita H Talasaz et al. Thromb Haemost. 2023 Jul.

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, p interaction = 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).

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Conflict of interest statement

D. V. reports consultant and speaker for BMS/Pfizer, Daiichi-Sankyo, Rovi, and Sanofi. Dr. Gupta received payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook inferior vena cava filter litigation. A. G. holds equity in a health care telecardiology startup, Heartbeat Health, Inc., and received consulting fees from Edwards LifeSciences. M. V. M. has received support from an institutional grant by the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). S. S. S. reports honoraria from Janssen and Chiesi and research grant support from the American Heart Association. G. P. has received research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific Corporation, Janssen, Namsa, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen. S. A. P. reports being on the Advisory Board for Abbott, Boston Scientific, Medtronic, CSI, Philips, Janssen; research grants: Abbott, Boston Scientific, Surmodics, TriReme Medical, Shockwave Medical; and receiving consulting fees from Terumo and Abiomed. M. M. received an unrestricted educational grant for research from Sanofi, Leo, and Rovi, and fees for participating in advisory meetings from Sanofi. A. J. K. reports institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr. Kirtane controlled the content. Personal: consulting from IMDS; Travel Expenses/Meals from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. S. B. reports unrestricted research grants from Bayer, Concept Medical, INARI, Boston Scientific, Bard, and Sanofi; honoraria from Bayer, Concept Medical, INARI, and Boston Scientific. B. W. V. T. has received research support from Novartis, Swedish Orphan Biovitrum, Olatec Therapeutics, Serpin Pharm, and R-Pharm. He has been a consultant of R-Pharm and Serpin Pharma. G. W. S. has received speaker or other honoraria from Cook, Terumo, and Orchestra Biomed; served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, and Cardiomech; and has received equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. G. Y. H. L. reports consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. H. M. K. reports personal fees from UnitedHealth, personal fees from IBM Watson Health, personal fees from Element Science, personal fees from Aetna, personal fees from Facebook, personal fees from Siegfried & Jensen Law Firm, personal fees from Arnold & Porter Law Firm, personal fees from Ben C. Martin Law Firm, personal fees from National Center for Cardiovascular Diseases, Beijing, ownership of HugoHealth, ownership of Refactor Health, contracts from the Centers for Medicare & Medicaid Services, grants from Medtronic and the Food and Drug Administration, grants from Medtronic and Johnson and Johnson, grants from Shenzhen Center for Health Information, and is a Venture Partner at FPrime. Outside the submitted work. B. B. is supported by a research grant from The Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital. B. B. reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. All other authors report no relevant disclosures.

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