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 |
List of Evidence/ Discussion
Peer-reviewed Studies
Randomized Controlled Trials
- 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
- 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)
- 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
Observational Results
- 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)
In vivo Preclinical SARS CoV-2
- 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