Atorvastatin versus placebo in ICU patients with COVID-19: ninety-day results of the INSPIRATION-S trial

Talasaz, A.H.; Sadeghipour, P.; Bakhshandeh, H.; Sharif-Kashani, B.; Rashidi, F.; Beigmohammadi, M.T.; ... ; Bikdeli, B. (2023)

Article / Letter to editor

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 (OR_ordinal: 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).

• statin
• atorvastatin
• lipid
• COVID-19
• functional limitations

• All authors: Talasaz, A.H.; Sadeghipour, P.; Bakhshandeh, H.; Sharif-Kashani, B.; Rashidi, F.; Beigmohammadi, M.T.; Moghadam, K.G.; Rezaian, S.; Dabbagh, A.; Sezavar, S.H.; Farrokhpour, M.; Abedini, A.; Aliannejad, R.; Riahi, T.; Yadollahzadeh, M.; Lookzadeh, S.; Rezaeifar, P.; Matin, S.; Tahamtan, O.; Mohammadi, K.; Zoghi, E.; Rahmani, H.; Hosseini, S.H.; Mousavian, S.M.; Abri, H.; Baghizadeh, E.; Rafiee, F.; Jamalkhani, S.; Amin, A.; Mohebbi, B.; Parhizgar, S.E.; Soleimanzadeh, M.; Aghakouchakzadeh, M.; Eslami, V.; Payandemehr, P.; Khalili, H.; Talakoob, H.; Tojari, T.; Shafaghi, S.; Tabrizi, S.; Kakavand, H.; Kashefizadeh, A.; Najafi, A.; Jimenez, D.; Gupta, A.; Madhavan, M.V.; Sethi, S.S.; Parikh, S.A.; Monreal, M.; Hadavand, N.; Hajighasemi, A.; Ansarin, K.; Maleki, M.; Sadeghian, S.; Barco, S.; Siegerink, B.; Spatz, E.S.; Piazza, G.; Kirtane, A.J.; Tassell, B.W.V.; Lip, G.Y.H.; Klok, F.A.; Goldhaber, S.Z.; Stone, G.W.; Krumholz, H.M.; Bikdeli, B.
• Date: 2023-05-12
• Journal: Thrombosis and Haemostasis
• Volume: 123
• Issue: 07
• Pages: 723 - 733
• DOI: doi:10.1055/a-2059-4844
• Link: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2059...