Atorvastatin Versus Placebo In Icu Patients With Covid19: Ninety-day Results Of The INSPIRATION-S Trial

Backgrounds: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a non-significant 16% reduction in 30-day composite of venous/arterial thrombosis or death in ICU patients with COVID-19. Thrombo-inflammatory response in 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 pre-specified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with Post-COVID-19 Functional Scale (PCFS). 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 to 1.01, P=0.05). Conclusions: 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.