Atorvastatin Efficacy in the Management of Mild to Moderate Hospitalized COVID-19: A Pilot Randomized Triple-blind Placebo- controlled Clinical Trial

Abstract

Background: Statins are first-line lipid-lowering agents with tolerable adverse reactions, low cost, and high availability worldwide. The potent anti-inflammatory, antioxidant, anti-thrombotic and immunomodulatory effects of statins propose them as an option to face COVID-19 infection. Objective: In this randomized triple-blind placebo-controlled clinical trial, we have investigated the atorvastatin efficacy in the management of mild to moderate hospitalized COVID-19 patients. Methods: In this study, 52 mild to moderate hospitalized COVID-19 patients who fulfilled the inclusion criteria were allocated to the treatment group to receive 40 mg atorvastatin orally once daily for two weeks (n=26) or the placebo group (n=26). Patients' symptoms and laboratory investigations were assessed at baseline and during the follow-up period. We also evaluated the duration of hospitalization and supplemental oxygen therapy as endpoints. Results: After 14-day of follow-up, the oxygen saturation (SaO2) was significantly higher, and the serum high sensitivity C-reactive protein (hs-CRP) level was lower in the treatment group compared with the placebo group. Moreover, at the end of the follow-up in the treatment group, the lymphocyte count was higher, and the duration of symptom resolution was shorter but not significant. Additionally, in the treatment group length of supplemental oxygen therapy and hospitalization duration were meaningfully shorter. Our results revealed that the mortality rate was almost twice higher in the placebo group compared with the treatment group, without any significant adverse drug reaction. Conclusion: Atorvastatin significantly reduces supplemental oxygen need, hospitalization duration, and serum hs-CRP level in mild to moderate hospitalized COVID-19 patients.

The impact of statin therapy on in‐hospital prognosis and endothelial function of patients at high‐to‐very high cardiovascular risk admitted for COVID‐19

“…Consistently, there is no clear evidence regarding the protective effects of in-hospital statin therapy (either continuation or introduction de novo) on the most severe forms of COVID-19. 13,14,[18][19][20][21]32,[45][46][47] Thus, as to whether statin-mediated protective effects in the context of COVID-19 may be time-…”

“…Interestingly, in the exploratory analyses of the present study, statin continuation during hospitalization was not associated with COVID‐19 outcomes. Consistently, there is no clear evidence regarding the protective effects of in‐hospital statin therapy (either continuation or introduction de novo) on the most severe forms of COVID‐19 13,14,18–21,32,45–47 . Thus, as to whether statin‐mediated protective effects in the context of COVID‐19 may be time‐dependent remains an open issue.…”

“…[11][12][13][14][15][16][17]19,[21][22][23][24] However, data on the relationship between preadmission statin use and the clinical course of COVID-19 in patients with high-to-very high CV risk, who are the most vulnerable with regard to COVID-19 complications, [25][26][27] albeit being consistent are still scarce. 22,[28][29][30][31] Moreover, although some previous studies have attempted to provide a direct insight into the possible biological mechanisms underlying the beneficial effects of statin therapy in the acute phase of COVID-19 (e.g., attenuation of inflammation and reduced myocardial injury), 17,22,32 the impact of statin-mediated endothelium protection on COVID-19 clinical outcomes has not been explored so far. Endothelial dysfunction has a crucial pathogenic role in the most severe clinical manifestations of COVID-19.…”

Treating COVID-19: Targeting the Host Response, Not the Virus

“…At least 24 observational studies have reported similar results [ 26 , 158 , 169 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 ]. The results of six RCTs of inpatient statin treatment have also been reported [ 199 , 200 , 201 , 202 , 203 , 204 ]. All of these results are summarized in Table 4 .…”

“…The relative risk of death was 0.90 (95% CI = 0.73–1.11; p value = 0.33). Daily statin treatment had no effect on mortality, but three of the six studies were very small [ 199 , 200 , 204 ], four used what was probably too low a dose of atorvastatin (20 mg instead of 40 mg) [ 199 , 200 , 201 , 202 ], and one dealt only with ICU patients [ 202 ], which may have been too late in the course of illness. Two RCTs examined simultaneous treatment with several drugs [ 200 , 203 ].…”