NEWS & PERSPECTIVE

Statin as a potential antithrombotic and immunomodulatory treatment for patients with COVID-19

In addition to progressive respiratory failure, emerging data suggested that COVID-19 patients are also at increased risk of cardiovascular complications and thrombotic events.1 Statins, which are known for their antithrombotic and immunomodulatory effect, were proposed to have a potential role as adjunctive therapy to patients suffering from COVID-19 infection.1 To clarify the opposing views on statin’s effectiveness among these patients, a meta-analysis has been carried out to summarize the existing evidence on the use of statins and their clinical outcomes of patients infected by COVID-19.2

While not conclusively proven, COVID-19 is shown to be associated with the dysregulation of the myeloid differentiation primary response protein (MYD) 88 pathway that results in overwhelming inflammation which has been associated with poor prognosis in other coronavirus infections.2 Statins are known inhibitors of MYD88 and could stabilize MYD88 levels in the presence of external stressors that can prevent the development of overwhelming inflammatory responses.2 Additionally, statins can also upregulate angiotensin-converting enzyme 2 (ACE2) expression and may be protective towards lung injury induced by the coronavirus.2

In earlier studies, statins were suggested to be potentially effective in decreasing influenza-related hospitalizations and deaths.1 During the 2009 H1N1 pandemic, statin therapy was associated with a reduced disease severity among hospitalized patients with some studies showing nearly half reduction in 30-day all-cause mortality with the use of statins in hospitalized patients with influenza infections.1 Based on its pleiotropic anti-inflammatory, antithrombotic, and immunomodulatory effects, statins may have a potential role as therapeutics to mitigate endothelial dysfunction and dysregulated inflammation in patients with COVID-19 infection.1 In particular, the same anti-inflammatory activity might improve outcomes in COVID-19 patients with increasingly severe illness, worsening respiratory failure, and increasing D-dimer, interleukin (IL)-6 levels and other factors that are associated with increased mortality.1

However, some researchers have argued that statins may activate the inflammasome pathway that could lead to an increased pro-inflammatory IL-18 level and promote a more severe case of COVID-19.2 Statins may also cause a deficiency of cell endogenous cholesterol content and enhance the accessibility for coronaviruses.2 To examine statin’s effectiveness in patients with COVID-19, 4 studies consisted of 8,990 COVID-19 patients were included in this meta-analysis.2 The pooled analysis revealed a significantly reduced hazard for fatal or severe disease in COVID-19 patients using statins when compared to those who did not (HR=0.70; 95% CI: 0.53-0.94).2 This preliminary finding suggests that statins can reduce fatal or severe disease by 30% and discredited the suggestion of harms with the use of statins in COVID-19 patients.2 This conclusion is also considered reliable as a large total number of COVID-19 patients from 4 studies in which 3 are large-scale studies that were adjusted extensively for multiple potential confounding factors were included.2

As patients with COVID-19 infection have an increased risk of cardiovascular complications and thrombotic events, it is of great importance to emphasize the continuation and adherence to statin therapy in patients with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes, or those at high risk of ASCVD.1,4 To avoid the high fatality rates of COVID-19 infection in those with established cardiovascular disease and diabetes that can reach an upwards of 10.8% and 7.3%, respectively, statin therapy should be continued in patients with suspected COVID-19 infection to mitigate the increased risk of cardiovascular events, such as acute cardiac injury, that are associated with COVID-19.4 Despite the limited evidence in proving a cause-effect relationship between the use of statins and reduced mortality in COVID-19, the potential benefits of using statins have far outweighed the very low risk of life-threatening side effects of statins, prompting the prescription of statins to all patients infected with COVID-19.4

Overall, the available evidence suggests that statin therapy of moderate-to-high intensity could be effective in treating patients with COVID-19.2 Patients who are placed on statin should adhere to the prescribed treatment regimen to mitigate the increased risk of cardiovascular events associated with COVID-19. Nevertheless, phase 3 randomized controlled trials should be considered to determine the best COVID-19 patient selection for statin therapy as well as the type and dose of statin to be given.1


References
  1. Lee KCH et al. Potential role of statins in COVID-19. International Journal of Infectious Diseases. 2020;96: 615-617.
  2. Kow CS et al. Meta-analysis of Effect of Statins in Patients with COVID-19. e 2020;00: 1−3.
  3. Mayo Clinic. Statin side effects: Weigh the benefits and risks. https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statin-side-effects/art-20046013. Accessed September 26, 2020.
  4. Virani SS. Is There a Role for Statin Therapy in Acute Viral Infections?. https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/09/is-there-a-role-for-statin-therapy-in-acute-viral-infections-covid-19. Accessed September 26, 2020.
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COVID-19
CARDIOVASCULAR COMPLICATIONS
THROMBOTIC EVENTS DRUGS INVOLVED
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