Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial. (7th January 2022)

• Record Type: Journal Article
• Other Names: author non-byline.; Bikdeli Behnood author non-byline.; Talasaz Azita H author non-byline.; Sharif-Kashani Babak author non-byline.; Rashidi Farid author non-byline.; Beigmohammadi Mohammad Taghi author non-byline.; Gohari Moghadam Keivan author non-byline.; Rezaian Somaye author non-byline.; Dabbagh Ali author non-byline.; Sezavar Seyed Hashem author non-byline.; Farrokhpour Mohsen author non-byline.; Bakhshandeh Hooman author non-byline.; Abedini Atefeh author non-byline.; Aliannejad Rasoul author non-byline.; Riahi Taghi author non-byline.; Yadollahzadeh Mahdi author non-byline.; Lookzadeh Somayeh author non-byline.; Rezaeifar Parisa author non-byline.; Matin Samira author non-byline.; Tahamtan Ouria author non-byline.; Mohammadi Keyhan author non-byline.; Zoghi Elnaz author non-byline.; Rahmani Hamid author non-byline.; Hosseini Seyed Hossein author non-byline.; Mousavian Seyed Masoud author non-byline.; Abri Homa author non-byline.; Sadeghipour Pardis author non-byline.; Baghizadeh Elahe author non-byline.; Rafiee Farnaz author non-byline.; Jamalkhani Sepehr author non-byline.; Amin Ahmad author non-byline.; Mohebbi Bahram author non-byline.; Parhizgar Seyed Ehsan author non-byline.; Soleimanzadeh Mahshid author non-byline.; Aghakouchakzadeh Maryam author non-byline.; Eslami Vahid author non-byline.; Payandemehr Pooya author non-byline.; Khalili Hossein author non-byline.; Talakoob Hamed author non-byline.; Tojari Taranom author non-byline.; Shafaghi Shadi author non-byline.; Fattah Ghazi Samrand author non-byline.; Tabrizi Sanaz author non-byline.; Kakavand Hessam author non-byline.; Kashefizadeh Alireza author non-byline.; Shahmirzaei Shaghayegh author non-byline.; Najafi Atabak author non-byline.; Fathi Mohammad author non-byline.; Jimenez David author non-byline.; Gupta Aakriti author non-byline.; Madhavan Mahesh V author non-byline.; Sethi Sanjum S author non-byline.; Parikh Sahil A. author non-byline.; Monreal Manuel author non-byline.; Hadavand Naser author non-byline.; Hajighasemi Alireza author non-byline.; Ansarin Khalil author non-byline.; Maleki Majid author non-byline.; Sadeghian Saeed author non-byline.; Piazza Gregory author non-byline.; Kirtane Ajay J author non-byline.; Van Tassell Benjamin W author non-byline.; Stone Gregg W author non-byline.; Lip Gregory Y H author non-byline.; Krumholz Harlan M author non-byline.; Goldhaber Samuel Z author non-byline.; Sadeghipour Parham author non-byline.;
• Is Part Of: BMJ. Volume 376(2022)
• Publication Date: 2022-01-07
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Periodicals; 610
• DOI: 10.1136/bmj-2021-068407
• Languages: English
• ISSNs: 0007-1447

Abstract

Abstract: Objective: To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). Design: INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. Setting: 11 hospitals in Iran. Participants: Adults aged ≥18 years with covid-19 admitted to the ICU. Intervention: Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. Main outcome measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. Results: Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). Conclusions: In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. Trial registration: ClinicalTrials.gov NCT04486508.