COVID-19 and Statins
Clarissa Chan, PharmD
Statin pharmacology is complicated and has many influences, including reductions in lipid levels, stabilization of blood vessel lining, and modest reductions in blood pressure. But it also has anti-inflammatory effects and antiviral properties for patients, said Russell E. Poland, PhD, who was part of a new study published in the March 2022 issue of the Journal of Hospital Medicine.
Poland, who is a senior lecturer at Harvard Medical School, and colleagues found in the retrospective study that discontinuation of ator-vastatin use during hospital admission was associated with increased COVID-19 mortality risk.
Existing research
According to a January 2012 study by Vandermeer and colleagues in The Journal of Infectious Diseases, the anti-inflammatory properties of statins may influence the decrease of influenza-related hospitalizations and deaths.
Additionally, a 2020 mBio study by Fedson and colleagues showed that statin treatment in patients with severe COVID‐19 infection may improve vascular and endothelial function through ACE2 upregulation. However, the recent CORONADO study found that type 2 diabetes patients hospitalized with COVID‐19 who took statins had an association with increased mortality, suggesting that statin use may cause harm.
Methods
The research team that Poland was a part of investigated repurposing atorvastatin to improve outcomes in patients with COVID-19. They collected data from patient’s electronic medical records.
Patients were 18 years and older with a laboratory-confirmed COVID-19 diagnosis who were admitted to HCA Healthcare–affiliated facilities across 21 U.S. states. To reduce confounding of cholesterol-modifying medications, only patients taking atorvastatin were included in the analysis.
Investigators assessed participating patients’ existing statin therapy discontinuation effects based on medication reconciliations upon admission and medications prescribed when discharged. Since patient-reported home medication regimens are not always accurate, patients admitted with no documented home atorvastatin use were excluded. No data were available for duration of outpatient atorvastatin therapy use so this was not analyzed.
Results
After excluding ineligible patients, the research team analyzed 146,413 patients comprised of 3 groups: continuous therapy (home + hospital atorvastatin use), discontinued therapy (home + no hospital atorvastatin use), and no statins (no home + no hospital atorvastatin use).
Patients in the no-statin-use group were at a lower risk of experiencing COVID-19 complications because they were typically younger—with a median age difference of 11 years—than those taking atorvastatin.
They also had a shorter median length of hospital stay (7.8 days vs. 9.6 days); had fewer cardiovascular comorbidities like coronary artery disease, lipidemias, atherosclerosis; and fewer had diabetes present on admission.
The primary analysis found continuous atorvastatin therapy was associated with 38% lower mortality odds in COVID-19 patients than discontinued atorvastatin therapy and 28% lower mortality odds than patients with no known statin use. No change in patient mortality odds was found for discontinued atorvastatin therapy versus no known statin use.
The secondary analysis showed that patients with COVID-19 who received continuous atorvastatin therapy had a 30% reduction in ventilation odds compared to those with discontinued atorvastatin therapy and a 24% reduction in ventilation odds compared to no known statin use. Patients with discontinued atorvastatin therapy had no change in ventilation odds versus no known statin use.
Takeaways
Consistent with other observational studies, this retrospective study demonstrates that continuous atorvastatin therapy is associated with decreased mortality or ventilation risk compared to discontinued therapy and no known statin use.
“The difference in outcome is too big to be causative; a few days of statin therapy in patients with acute myocardial infarction does not have a big enough effect to reduce mortality in hospital,” said Christopher Cannon, MD, professor of medicine at Harvard Medical School, who was not part of the study. “Since total mortality is reduced after 5 years [of statin use], this is likely an association and has nothing to do with the effect of the statin.”
Overall, this study is consistent with NIH recommendations to continue treating patients with statins in cases of acute management of COVID-19 unless there is proven evidence to suggest discontinuing statin therapy. ■