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... Show moreBackground 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). Show less
Introduction: Patients affected with severe forms of coronavirus disease 2019 (COVID-19) suffer from a wide range of sequelae, from limited airway diseases to multiple organ failure. These sequelae... Show moreIntroduction: Patients affected with severe forms of coronavirus disease 2019 (COVID-19) suffer from a wide range of sequelae, from limited airway diseases to multiple organ failure. These sequelae may create exercise limitation, impair the daily activity and thus impact the mental health and the social life. However, the extent of functional limitations and depressive symptoms are understudied especially in patients with COVID-19 after intensive care unit (ICU) hospitalization. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) was a clinical trial that randomized ICU patients with COVID-19 to intermediate-dose vs standard-dose anticoagulation. In the current study, we assessed the interval change in 30-day and 90-day functional limitations based on the post-COVID-19 functional status scale (PCFS) and depressive symptoms based on the Patient Health Questionnaire-2 (PHQ-2) in the trial participants. We also assessed the effect of intermediate-dose vs standard-dose prophylactic anticoagulation on the functional outcomes and depressive symptoms. Results: Of 600 randomized patients in INSPIRATION, 375 (age: 62 years; 42% women) participated in the functional status study. 195 patients died during the 90-day follow up (191 by day 30). Among survivors, between day 30 and day 90, the proportion of patients with moderate-to-severe functional limitation (PCSF grade 3-or-4) decreased from 20.0% to 4.8% (P <0.001) and PHQ-2 >= 3 decreased from 25.5% to 16.6% (P = 0.05). The proportion of patients with no functional limitations (PCFS grade 0) increased (4.2% to 15.4%, P<0.001). Intermediate-dose compared with standard-dose prophylactic anticoagulation did not impact the 90-day proportion of patients with PCFS grade 3-or-4 (5.3% vs 4.2%; odds ratio (OR), 1.20, [95% CI, 0.46-3.11]; P = 0.80) or PHQ-2 >= 3 (17.9% vs 15.3%; OR, 1.14, [95% CI, 0.79-1.65]; P = 0.14), with similar results when accounting for study center. Conclusion: In patients with COVID-19 admitted to the ICU, functional limitations and depressive symptoms were common at 30-day follow-up and had some improvement by 90-day follow-up among survivors. Intermediate-dose compared to standard-dose prophylactic anticoagulation did not improve functional outcomes. Show less
