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In COVID-19 patients admitted to intensive care, atorvastatin 20 mg / d did not significantly reduce the risk of venous or arterial thrombosis, extracorporeal membrane oxygenation (ECMO) treatment, or all-cause mortality compared with placebo. the INSPIRATION-S study.
However, there is a suggestion of benefit in the subgroup of patients who were treated within 7 days of the onset of COVID-19 symptoms.
The study was presented by Behnood Bikdeli, MD, Brigham and Women’s Hospital, Boston, Massachusetts, on May 16 at the Virtual American College of Cardiology (ACC) 2021
He explained that COVID-19 is characterized by a violent immune response and that there is a potential for thrombotic events due to enhanced endothelial activation and prothrombotic status.
“In this context, it is interesting to think of statins as potential agents to be studied in COVID-19, because in addition to having lipid-lowering effects, they are also thought to have anti-inflammatory and antithrombotic effects,” he said.
In the HARP-2 study of simvastatin in acute respiratory distress syndrome (ARDS) published several years ago, the main results were neutral, but in the subgroup of patients with hyperinflammatory ARDS there was a reduction in mortality with simvastatin compared with placebo, Bickdeli noted.
In addition, in a series of observational studies in patients with COVID-19, statin use was associated with a reduction in mortality among hospitalized patients. However, there is limited high-quality data to guide clinical practice, he said.
The INSPIRATION study, conducted in 11 hospitals in Iran, had a two-factor structure for examining different anticoagulant strategies and the use of atorvastatin for patients with COVID-19 in the intensive care unit.
In the anticoagulant portion of the study, which was published in JAMA last month there was no difference in the primary endpoint of the intermediate dose and the standard dose of enoxaparin.
For the statin portion of the study (INSPIRATION-S), 605 patients were randomized to receive atorvastatin 20 mg daily or placebo. Patients who have previously taken statins are excluded. The baseline characteristics are similar for the two groups, with about a quarter of patients taking aspirin and more than 90% taking steroids.
The results showed that atorvastatin was not associated with a significant reduction in primary outcome – composition of assigned venous or arterial thrombosis, ECMO treatment or mortality within 30 days – which occurred in 32.7% of the statin group versus 36, 3% of the placebo group (ratio of odds [OR], 0.84; P = .35).
Atorvastatin was not associated with significant differences in any of the individual components of the primary constituent endpoint. There is also no significant difference in any of the safety endpoints, which involves heavy bleeding and elevated liver enzyme levels.
The analyzes of the subgroups were mostly in line with the main findings, with one exception.
In the subgroup of patients who appeared within the first 7 days of the onset of COVID-19 symptoms, there was a hint of a potential protective effect with atorvastatin.
In this group of 171 patients, the primary endpoint was observed in 30.9% of those receiving atorvastatin versus 40.3% of those receiving placebo (OR, 0.60; P = .055).
“This is an interesting observation and is plausible because these patients may be in different stages of COVID-19 disease. But we need to be aware of the many comparisons and this needs to be further explored in future studies,” Bickelli said.
Is a higher dose in less sick patients a better strategy?
Discussing the study during the ACC presentation, Dr. Binita Shah said that the importance of including patients with COVID-19 in clinical trials was paramount, but that these patients in the intensive care unit may not have been the correct population. in which to test a statin.
“Maybe it’s too late for these very sick patients. Trying to control the inflammatory cytokine storm and interacting with thrombosis at this point is very difficult,” Shah said.
She suggested that it might be appropriate to try statins at an earlier stage of the disease to prevent the inflammatory process, instead of trying to stop it once it has started.
Shah also questioned the use of such a low dose of atorvastatin for these patients. “In the cardiovascular literature – at least in the ACS [acute coronary syndrome] – High doses of statins are used to see the short-term benefits. In this highly inflammatory environment, I wonder if a high-intensity regimen would be more beneficial, ”she suggested.
Bikdeli responded that a low dose of atorvastatin was chosen because several antiviral agents, such as ritonavir, were initially used in patients with COVID-19, and these drugs were associated with elevated liver enzymes.
“We didn’t want to exacerbate this with high doses of statins,” he said. “But we have now established the safety profile of atorvastatin in these patients, and in retrospect, yes, a higher dose may have been better.”
The INSPIRATION study was funded by the Rajaie Cardiovascular Medical and Research Center, Tehran, Iran. Bikdeli does not disclose relevant financial relationships.
American College of Cardiology (ACC) 2021 Scientific session: Presented on May 16, 2021
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