Statins are medications widely used in the management of cardiovascular diseases and metabolic syndrome. Statins help lower serum lipids by blocking HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase), the rate-limiting enzyme of cholesterol biosynthesis.
They are also known to have pleiotropic effects, including immunomodulation, anti-inflammation, upregulation of angiotensin-converting enzyme 2 (ACE2) receptor expression, antioxidation, and antithrombosis.
Theoretically, since ACE2 is the entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), chronic use of statins could increase susceptibility to COVID-19. However, ACE2 also mediates the conversion of angiotensin II to angiotensin (1–7) peptide, which protects lung damage. Thus, the net influence of the use of statins on COVID-19 is not evident. The use of statins to influence the clinical course and prognosis of COVID-19 is increasingly drawing the attention of researchers.
Investigating the effect of statin use on COVID-19 outcomes
Researchers from the Republic of China recently conducted a study to investigate the association between statin use and COVID-19 outcomes and identify the population subgroup that can benefit from the use of statins. The research is published in the open-access journal, Annals of Medicine.
They performed a systematic review and meta-analysis of previously published studies on statin users and COVID-19 outcomes. They used the generic inverse variance method for meta-analyses with random-effects modeling. The key outcomes were the need for intensive care unit (ICU) care, the need for invasive mechanical ventilator (IMV) support, and mortality. All these outcomes were determined as dichotomous variables.
Findings show that statin use is significantly associated with reduced COVID-19 mortality
The researchers reviewed 28 observational studies that covered data from 63,537 COVID-19 patients. The results showed that statin use was significantly associated with reduced all-cause mortality and the need for IMV in COVID-19 patients. However, the use of statins was not associated with the need for ICU care. Subgroup analysis identified five types of studies in which patients taking statins had lower chances of death.
Subgroup analysis showed that the use of statins prevented more deaths in studies that had a case fatality rate (CFR) under 20% compared to studies with a CFR of over 20%. This implies that the benefit of statin use is likely more significant when the COVID-19 mortality rate in the community is decreased.
The meta-analyses also reveals that while the use of statins was associated with reduced need for IMV, it did not prevent ICU admission. Statins offer lung protection, likely by upregulating ACE2 expression, which leads to increased angiotensin (1–7) production and hence decreases the need for ventilator support. However, they did not reduce other non-pulmonary events, including cardiovascular complications or sepsis.
Study confirms that patients may safely continue statin use during COVID-19 infection
According to the authors, the findings on statins associated with reduced COVID-19 mortality agree with previous studies' results. Statin users are usually older compared to non-statin users and have more comorbidities, both of which are risk factors for COVID-19 mortality. Thus, the association between the use of statins and COVID-19 mortality may not be obvious as the increased risks from host factors may counter the protective effect of statins.
The findings of this analysis showed that participants with COVID-19 in 5 types of studies had lower odds of death while on statins. This shows that individuals taking statins may not need to discontinue statin use on admission during COVID-19 infection. The authors believe that randomized controlled trials are required to clarify the causal effect between the use of statins and severe COVID-19 outcomes.
In terms of limitations, the authors mentioned that although currently, available evidence shows that statins may be beneficial for COVID-19 patients, there is no clarity when it comes to a particular drug name, dose, or duration.
Also, since a significant portion of the study participants had comorbidities such as diabetes or cardiovascular diseases, they might have been on concomitant medications such as ACE inhibitors, metformin, and angiotensin II receptor blockers. These medications have been shown to influence COVID-19 mortality and prognosis.
"The influence of interaction between statins and co-medications on COVID-19 remains unclear and might impact the estimate of statins' effect. Future RCTs are needed to solve the limitations mentioned above."