Atorvastatin use in patients infected with COVID-19 and with more severe disease in an intensive care unit (ICU) does not lead to a significant reduction in adverse outcomes, according to research by a team from the Rajaie Cardiovascular Medical and Research Centre, Tehran, Iran.
Hydroxymethylglutaryl coenzyme A reductase inhibitors (or statins), have a number of physiological effects including a direct antithrombotic action in models of arterial and venous thrombosis which is unrelated to their cholesterol-lowering activity, as well as anti-inflammatory properties.
Furthermore, a 2021 systematic review also identified additional pleiotropic effects including antiviral and immunomodulatory that might be of benefit to those with COVID-19.
With a potentially beneficial effect on COVID-19, the Iranian team sought to examine the impact of atorvastatin on thromboembolic events or death, in patients with the most severe form of COVID-19, i.e., those admitted to ICU.
Their study was part of the INSPIRATION trial which had two arms: one that explored the effect of prophylactic anticoagulation and the other focusing on the use of atorvastatin.
The team recruited patients 18 years and older, with a PCR confirmed COVID-19 infection in ICU in whom there was no baseline therapeutic need for a statin. Enrolled patients were then randomised 1:1 to atorvastatin 20 mg daily or matching placebo and followed for 30 days after randomisation.
For patients requiring mechanical ventilation, the drug was delivered via a nasogastric or orogastric tube. The primary outcome of interest was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation or all-cause mortality within 30 days of randomisation.
Findings
A total of 587 patients with a median age of 57 years (44% female) were randomised to atorvastatin or placebo and treatment was used for a median of 21 days and slightly less, at 19 days for placebo. The median length of stay within ICU was five days in both groups.
After 30 days, the primary outcome had occurred in 95 (33%) of patients assigned to atorvastatin and 108 (36%) of those given placebo (odds ratio, OR = 0.84, 95% CI 0.58 – 1.21, p = 0.35). The results for the primary outcome were largely driven by mortality, with 31% and 35% of deaths in the atorvastatin and placebo groups respectively although no patients required extracorporeal membrane oxygenation.
The use of imaging tests such as computed tomography pulmonary angiograms and doppler, revealed a similar level of venous thromboembolism diagnoses in the two groups (20% vs 20%, p = 0.64). There was also no difference in the incidence of arterial thrombosis. In subgroup analysis, there were no sex-related differences, among patients older/younger than 65 years, smokers or in those with/without obesity or diabetes.
The authors speculated that the reason atorvastatin did not produce the desired effect, might have been cause it only produces a small protective effect which was undetectable. Alternatively, they thought that statins were only of benefit in the early stages of COVID-19 infection prior to the inflammatory response which led to irreversible damage.
Citation
NSPIRATION-S investigators. Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial. BMJ 2022.
