Atorvastatin: A potential treatment in COVID-19?
For patients with COVID-19 admitted to intensive care, giving atorvastatin 20 mg/d did not result in a significant reduction in risk for venous or arterial thrombosis, for treatment with extracorporeal membrane oxygenation (ECMO), or for all-cause mortality, compared with placebo in the INSPIRATION-S study.
However, there was a suggestion of benefit in the subgroup of patients who were treated within 7 days of COVID-19 symptom onset.
The study was presented by Behnood Bikdeli, MD, Brigham and Women’s Hospital, Boston, on May 16 at the annual scientific sessions of the American College of Cardiology.
He explained that COVID-19 is characterized by an exuberant immune response and that there is a potential for thrombotic events because of enhanced endothelial activation and a prothrombotic state.
“In this context, it is interesting to think about statins as potential agents to be studied in COVID-19, because as well as having lipid-lowering actions, they are also thought to have anti-inflammatory and antithrombotic effects,” he said.
In the HARP-2 trial of simvastatin in acute respiratory distress syndrome (ARDS), published a few years ago, the main results were neutral, but in the subgroup of patients with hyperinflammatory ARDS, there was a reduction in mortality with simvastatin in comparison with placebo, Dr. Bikdeli noted.
Moreover, in a series of observational studies of patients with COVID-19, use of statins was associated with a reduction in mortality among hospitalized patients. However, there are limited high-quality data to guide clinical practice, he said.
The INSPIRATION study, conducted in 11 hospitals in Iran, had a two-by-two factorial design to investigate different anticoagulant strategies and the use of atorvastatin for COVID-19 patients in the ICU.
In the anticoagulation part of the trial, which was published in JAMA in March 2020, there was no difference in the primary endpoint of an intermediate dose and standard dose of enoxaparin.
For the statin part of the trial (INSPIRATION-S), 605 patients were randomly assigned to receive atorvastatin 20 mg daily or placebo. Patients who had been taking statins beforehand were excluded. Baseline characteristics were similar for the two groups, with around a quarter of patients taking aspirin and more than 90% taking steroids.
Results showed that atorvastatin was not associated with a significant reduction in the primary outcome – a composite of adjudicated venous or arterial thrombosis, treatment with ECMO, or mortality within 30 days – which occurred in 32.7% of the statin group versus 36.3% of the placebo group (odds ratio, 0.84; P = .35).
Atorvastatin was not associated with any significant differences in any of the individual components of the primary composite endpoint. There was also no significant difference in any of the safety endpoints, which included major bleeding and elevations in liver enzyme levels.
Subgroup analyses were mostly consistent with the main findings, with one exception.
In the subgroup of patients who presented within the first 7 days of COVID-19 symptom onset, there was a hint of a potential protective effect with atorvastatin.
In this group of 171 patients, the primary endpoint occurred in 30.9% of those taking atorvastatin versus 40.3% of those taking placebo (OR, 0.60; P = .055).
“This is an interesting observation, and it is plausible, as these patients may be in a different phase of COVID-19 disease. But we need to be cognizant of the multiplicity of comparisons, and this needs to be further investigated in subsequent studies,” Dr. Bikdeli said.
