Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial
Authors: Talasaz Azita H. , Sadeghipour Parham , Bakhshandeh Hooman , Sharif-Kashani Babak , Rashidi Farid , Beigmohammadi Mohammad Taghi , Moghadam Keivan Gohari , Rezaian Somaye , Dabbagh Ali , Sezavar Seyed Hashem , Farrokhpour Mohsen , Abedini Atefeh , Aliannejad Rasoul , Riahi Taghi , Yadollahzadeh Mahdi , Lookzadeh Somayeh , Rezaeifar Parisa , Matin Samira , Tahamtan Ouria , Mohammadi Keyhan , Zoghi Elnaz , Rahmani Hamid , Hosseini Seyed Hossein , Mousavian Seyed Masoud , Abri Homa , Sadeghipour Pardis , Baghizadeh Elahe , Rafiee Farnaz , Jamalkhani Sepehr , Amin Ahmad , Mohebbi Bahram , Parhizgar Seyed Ehsan , Soleimanzadeh Mahshid , Aghakouchakzadeh Maryam , Eslami Vahid , Payandemehr Pooya , Khalili Hossein , Talakoob Hamed , Tojari Taranom , Shafaghi Shadi , Tabrizi Sanaz , Kakavand Hessam , Kashefizadeh Alireza , Najafi Atabak , Jimenez David , Gupta Aakriti , Madhavan Mahesh V. , Sethi Sanjum S. , Parikh Sahil A. , Monreal Manuel , Hadavand Naser , Hajighasemi Alireza , Ansarin Khalil , Maleki Majid , Sadeghian Saeed , Barco Stefano , Siegerink Bob , Spatz Erica S. , Piazza Gregory , Kirtane Ajay J. , Tassell Benjamin W. Van , Lip Gregory Y. H. , Klok Frederikus A. , Goldhaber Samuel Z. , Stone Gregg W. , Krumholz Harlan M. , Bikdeli Behnood 
Published: March 2023

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).