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

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,

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).

Informations de copyright

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Déclaration de conflit d'intérêts

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.