Can atorvastatin save COVID-19 patients in intensive care?

Use of atorvastatin in adults with COVID-19 admitted to the intensive care unit (ICU) is safe but does not result in a marked decrease in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all-cause mortality, a study has shown.

However, “[a]s the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded,” the researchers said.

A multicentre, randomized controlled trial with a 2x2 factorial design (INSPIRATION/INSPIRATION-S) was conducted in 11 hospitals in Iran. Adults with COVID-19 admitted to the ICU received either atorvastatin 20 mg orally once daily or placebo, continued for 30 days from randomization regardless of hospital discharge status.

Between 29 July 2020 and 4 April 2021, 605 patients underwent statin randomization in the INSPIRATION-S trial, of whom 587 (median age 57 years, 44 percent women) were included in the primary analysis: 290 were assigned to atorvastatin and 297 to placebo.

The primary outcome (a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all-cause mortality within 30 days from randomization) occurred in 95 (33 percent) patients on atorvastatin and 108 (36 percent) on placebo (odds ratio [OR], 0.84, 95 percent confidence interval [CI], 0.58‒1.21). [BMJ 2022;376:e068407]

Ninety (31 percent) and 103 (35 percent) patients died in the atorvastatin and placebo groups, respectively (OR, 0.84, 95 percent CI, 0.58‒1.22), while six (2 percent) and nine (3 percent) had venous thromboembolism, respectively (OR, 0.71, 95 percent CI, 0.24‒2.06). None of the patients in either group developed myopathy. Additionally, five (2 percent) patients on atorvastatin and six (2 percent) on placebo had increased levels of liver enzyme (OR, 0.85, 95 percent CI, 0.25‒2.81).

These findings can be explained by the following: first, statin treatment could have had a small protective role; second, it was possible that statins were beneficial in early COVID-19 prior to the irreversible damage cause by inflammatory response; third, the effect of statins on venous or arterial thrombosis or mortality could have become apparent beyond the 30 days of follow-up. [JAMA 2020;324:1330-1341; Circ Res 2020;126:1443-1455]

“It is conceivable that lipid modulating agents might affect the risk of thrombosis or inflammation in patients with COVID-19,” the researchers said. “Several ongoing randomized controlled trials are assessing the effects of lipid modulating agents, including statins, omega 3 fatty acids, fibrates, and niacin across the spectrum of illness severity in COVID-19.” [Metabolism 2020;113:154375; J Am Coll Cardiol 2021;78:1635-1654]

Although a distinct treatment effect for statins based on the underlying inflammatory biomarkers was possible, INSPIRATION-S did not have a prespecified biomarker study. [Lancet Respir Med 2018;6:691-698; Lancet Respir Med 2020;8:1209-1218]

“Since INSPIRATION-S focused on patients with COVID-19 admitted to the ICU, the findings are not generalizable to other patient subgroups, including those admitted to medical wards or outpatients with COVID-19,” the researchers said.