Statins

Last review completed on
April 10th, 2020
Therapy Description

NOTE: The Level of Evidence below is for non-Covid-19 ARDS. To date, there are NO studies that have evaluated statins in any form of SARS-CoV

Recommendation

Evidence does not support that the addition of statin therapy treatment will improve clinical outcomes in ARDS, and there is no data supporting use for COVID-19 specifically. Patients diagnosed with COVID-19 who were already on statin therapy prior should have their statin therapy continued.

Clinical Circumstances
Level of Evidence
= Supporting use article = Neutral Article  = Contradicting use article

Step 1 - In vitro SARS CoV-1/2 and MERS-CoV Step 2 - In vivo MERS-CoV Step 3 - In vivo SARS CoV-2


Contradicting Use articleContradicting Use article
List of Evidence/ Discussion

Peer-reviewed Studies

Level 5: Random Controlled Trial SARS CoV-2 articles listed below Randomized Controlled Trials
  1. Contradicting Use article Craig TR, Duffy MJ, Shyamsundar M, et al. A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med. 2011;183(5):620-6.
    • n= 60 patients with ALI and ARDS diagnosis within 48 hours
    • Simvastatin 80mg vs. placebo; simvastatin showed no statistically significant reduction in oxygenation index by day 14, but did show significant reduction in SOFA score at day 14 compared to placebo (p=0.01). Simvastatin also resulted in significant improvement in coagulation, renal, and cardiovascular organ dysfunction, as well as significant reduction in CRP levels at day 14 (p=0.0004)
    • At day 14, the simvastatin group had less patients requiring dobutamine (0% vs. 37.5%, p= 0.09) and significantly less patients requiring norepinephrine (0% vs. 33%, p= 0.05, NNT = 3.03)
    • No statistically significant difference in duration of ventilation, ICU stay, or hospital stay between the two groups
    • The two groups were identical in incidence of hospital survival
  2. Supporting Use article Shyamsundar M, Mckeown ST, O'kane CM, et al. Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers. Am J Respir Crit Care Med. 2009;179(12):1107-14.
    • n= 20 healthy volunteers, induced acute lung injury via inhalation of lipopolysaccharide
    • Simvastatin 40/80mg vs. placebo daily for 4 days prior to lipopolysaccharide inhalation, simvastatin showed statistically significant reduced levels of inflammatory markers:  BALF tumor necrosis factor-alpha (p=0.04), matrix metalloproteinases 7, 8, and 9 (p= 0.03, 0.007 and 0.04 respectively), plasma CRP (p=0.03), and BALF neutrophil count (8.5 vs 3.0, p= 0.05)
  3. Contradicting Use article Mcauley DF, Laffey JG, O'kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371(18):1695-703.
    • n= 540 patients with ARDS within 48 hours
    • Simvastatin 80mg vs. placebo, no significant difference in mean number of ventilator-free days, days free of non-pulmonary organ failure, or mortality in 28 days
    • No significant difference in CRP levels at baseline, day 3, and day 7, no significant between-group difference in change in CRP 
Level 4: Observational SARS CoV-2 articles listed below Observational Results
  1. Supporting Use article Mansur A, Steinau M, Popov AF, et al. Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study. BMC Med. 2015;13:128.
    • n= 404 patients with sepsis developed ARDS, 27% (109 patients) were on statin therapy that was continued throughout hospital course (primarily simvastatin)
    • 10% of patients without statin therapy and 12% of patients with statin therapy had viral ARDS; ARDS type was primarily gram-negative bacterial 
    • In severe ARDS, survival at 28 days following onset of sepsis was significantly higher in patients on statin therapy, p=0.0205 after propensity score matching (28 day survival was not significantly improved in the mild and moderate ARDS groups)
    • In severe ARDS, absence of statin therapy was an independent prognostic indicator of 28-day mortality risk (p= 0.0156, HR = 5.46)
Level 3: In vivo SARS CoV-2 articles listed below In vivo Preclinical SARS CoV-2
  1. Supporting Use article Jacobson JR, Barnard JW, Grigoryev DN, Ma SF, Tuder RM, Garcia JG. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol. 2005;288(6):L1026-32.
    • Anesthetized mice exposed to simvastatin 5mg/kg, simvastatin 20mg/kg or placebo 24 hours before induction of lung inflammation via lipopolysaccharide administration
    • Administration of simvastatin 20mg/kg resulted in 50% decrease in BAL albumin, which indicates favorable effects on LPS-induced vascular leak. Simvastatin 20mg/kg also showed less lavage MPO activity and total neutrophils