Atorvastatin does not reduce mortality in COVID-19

Patients who were hospitalised with COVID-19 and given atorvastatin fared no better than patients who were given a placebo, with respect to reducing venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality [1]. Results of the INSPIRATION trial also found no difference between the groups in terms of the main safety outcomes of clinically diagnosed myopathy or elevated liver enzymes.

Some patients with COVID-19 exhibit a dramatic immune response, resulting in increased thrombotic events and a hyperinflammatory state. The intensity of the immune response can lead to the development of acute respiratory distress syndrome (ARDS) and ultimately death. Statins are known to have pleiotropic effects that include both anti-inflammatory and anti-thrombotic effects. Previous studies have shown a beneficial effect of statins on hyper-inflammatory phenotypes of ARDS (but not hypo-inflammatory phenotypes) [2,3]. Furthermore, antecedent statin use has been associated with decreased mortality in COVID-19 hospitalised patients. Dr Behnood Bikdeli (Brigham and Women’s Hospital, MA, USA) and colleagues aimed to investigate whether statins could benefit patients who were severely affected with COVID-19.

The INSPIRATION trial (NCT04486508) randomised 605 patients who were critically ill with COVID-19 to receive either 20 mg of atorvastatin daily (n=303) or a placebo (n=302) over 30 days. Of the original 303 patients in the atorvastatin arm, 290 were included in the prespecified primary analysis; of the original 302 patients in the placebo arm, 297 were included in the prespecified primary analysis.

The primary endpoint was a composite of 30-day venous or arterial thrombosis, treatment with ECMO, or all-cause mortality. In the atorvastatin arm, 95/290 (32.7%) reached the primary endpoint compared with 108/297 (36.3%) in the placebo arm (HR 0.84; 95% CI 0.63–1.11; P=0.22).

The main safety outcomes were a rise in liver enzymes of >3 times normal and clinically diagnosed myopathy. In the atorvastatin group, only 5 (1.7%) patients experienced a rise in liver enzymes compared with 6 (2.0%) in the placebo group. No patients were diagnosed with myopathy.

The investigators concluded that the administration of 20 mg atorvastatin daily to ICU-admitted patients with COVID-19 was no more beneficial than a placebo. However, they suggested that a smaller treatment effect could not be excluded. They identified the need for further research that explores the potential role of statins if administered sooner; that is, before the hyperinflammatory pathway is activated.

1. 
   
   1. Bikdeli B. Atorvastatin vs Placebo in Critically-ill Patients with Covid-19: The Inspiration-S Double Blind Randomised Controlled Trial. Abstract 409-16, ACC 2021 Scientific Session, 15–17 May.
   2. Heijnen NFL, et al. J Thorac Dis 2019;11(Suppl 3):S296-S299.
   3. Calfee CS, et al. Lancet Respir Med 2018;6(9):691-698.

 

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Posted on 9 July, 20216 September, 2023