Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs). Methods We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted. Results Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation. Conclusion Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.

Effect of IL-6R blockade on plasma lipids and clinical outcomes among hospitalized patients with COVID-19 infection

“…It has been postulated that a protective effect of statins may result from their anti-inflammatory effects, possibly via decreasing lipid particle clearance of lipogenic viral particles whose clearance is slowed and half-life prolonged, and/or a direct inhibitory effect on SARS-CoV-2 infectivity ( 39 , 40 ). However, a meta-analysis of randomized controlled trials observed no benefit in adding statins to COVID-19 treatment ( 41 ), a finding further supported by recently published studies ( 42 , 43 ). In a small study, the use of proprotein convertase subtilisin/kexin type 9 inhibitors was shown to increase survival for 30 patients with COVID-19; however, additional larger studies are required to confirm this finding ( 44 ).…”