Statin therapy may reduce mortality in hospitalized COVID-19 patients

Use of statins helps prevent deaths in patients hospitalized with COVID-19, as shown by the results of a systematic review and meta-analysis.

"In patients hospitalized with COVID-19, adjunctive statin therapy significantly reduced case-fatality rate and reduced WHO scale score,” the researchers said. “There were no significant differences in length of hospital stay, elevation of liver enzymes, and C-reactive protein (CRP) levels.”

For this study, the databases of Medline, Embase, Cochrane, and ClinicalTrials.gov were searched from inception to late April 2024 for randomized controlled trials (RCTs) comparing statins with no statin use in patients hospitalized with COVID-19. The researchers then pooled the risk ratios (RRs) and hazard ratios (HRs), with 95 percent confidence intervals (CIs), through a random-effects model.

Seven RCTs, which involved a total of 4,262 patients, met the eligibility criteria. Of the participants, 2,645 (62 percent) were randomly assigned to receive statin therapy. [Am J Med 2024;137:966-973.e11]

Statin use resulted in a significant reduction in case-fatality rates (RR, 0.88, 95 percent CI, 0.80–0.98; I², 0 percent) relative to no statin use. A time-to-event analysis revealed similar results (HR, 0.86, 95 percent CI, 0.75–0.99; I², 0 percent). Additionally, use of statins led to a significant reduction in the WHO scale at 15 days (mean difference, –0.27, 95 percent CI, –0.54 to –0.01; I², 0 percent).

On the other hand, the two groups showed no statistically significant difference in length of hospital stay, elevation of liver enzymes, and CRP levels.

“Although individual studies included in this meta-analysis have not found any statistically significant difference in overall death, we found that adjunctive statin therapy led to a significant relative risk reduction of 12 percent in this important endpoint,” the researchers said.

“This could be attributed to the high statistical power given the inclusion of the largest RCT up to date, REMAP-CAP, that found a 91.3-percent probability of superiority of statin group compared with the control group in death, but without statistical significance,” they added.

Inflammation

Patients with COVID-19 are vulnerable to inflammatory damage by way of the bloodstream. [Am J Med 2024;137:966-973.E11]

Statins could regulate such inflammation through the following potential mechanisms: 1) inhibition of the NF-κB pathway and platelet aggregation; 2) the cholesterol-lowering effects, 3) interference in proinflammatory transcription factors, 4) reduction of the plasminogen activator inhibitor-1, and 5) potential disruption of SARS-COV 2 membrane lipid rafts.

"Collectively, these potential effects in the inflammatory cascade and the enhancement in endothelial function may explain the reduction in death rate,” the researchers said. “However, further mechanistic studies are warranted.” [Front Immunol 2021;12:742941; Biochimie 2021;189:51-64]

The COVID-19 pandemic affected 771 million individuals, which led to approximately 6.9 million deaths worldwide. After transitioning into an endemic respiratory infection, COVID-19 patients were often characterized by intense inflammatory responses with potential organ damage. [Front Immunol 2021;12:742941; https://data.who.int/dashboards/covid19/cases]