Atorvastatin therapy in COVID-19 adult inpatients: A double-blind, randomized controlled trial

Abstract

Introduction Efficacious therapies are urgently required to tackle the coronavirus disease 2019 (COVID-19). This trial aims to evaluate the effects of atorvastatin in comparison with standard care for adults hospitalized with COVID-19. Methods We conducted a randomized controlled clinical trial on adults hospitalized with COVID-19. Patients were randomized into a treatment group receiving atorvastatin + lopinavir/ritonavir or a control group receiving lopinavir/ritonavir alone. The primary outcome of the trial was the duration of hospitalization. The secondary outcomes were the need for interferon or immunoglobulin, receipt of invasive mechanical ventilation, and O2 saturation (O2sat), and level of C-reactive protein (CRP) which were assessed at the onset of admission and on the 6th day of treatment. Results Forty patients were allocated and enrolled in the study with a 1 to 1 ratio in atorvastatin + lopinavir/ritonavir and lopinavir/ritonavir groups. Clinical and demographic characteristics were similar between the two groups. CRP level was significantly decreased in the lopinavir/ritonavir + atorvastatin group (P < 0.0001, Cohen’s d = 0.865) so that there was a significant difference in CRP level on the 6th day between the two groups (P = 0.01). Nevertheless, there was no significant difference in O2sat on day 6. Although the duration of hospitalization in the lopinavir/ritonavir + atorvastatin group was significantly reduced compared to the control group (P = 0.012), there was no significant difference in the invasive mechanical ventilation reception and the need for interferon and immunoglobulin. Conclusion Atorvastatin + lopinavir/ritonavir may be more effective than lopinavir/ritonavir in treating COVID-19 adult hospitalized patients.

Survival of the hospitalized patients with COVID‐19 receiving atorvastatin: A randomized clinical trial

“…Our results were in contrast with Davoodi et al's study 28 that conducted a similar study on COVID‐19 inpatients and evaluated the impact of adding atorvastatin to standard therapy, lopinavir/ritonavir, on the duration of hospitalization. However, the dose of atorvastatin (40 mg daily) and the number of enrolled patients ( n = 20 in each group) were different in our study.…”

“… 39 Both lopinavir and ritonavir are potent CYP3A inhibitors and their concurrent administration with statins raises statin concentrations and the risk of toxicity. 40 It is a predictable drug interaction and based on references atorvastatin 20 mg/day 41 was selected herein, however, it was better we evaluated enrolled patients for rhabdomyolysis, an outcome that was missed in this study, and its measuring was just limited to symptomatic patients during the study, while Davoodi et al 28 excluded patients with myositis and liver injury form their study.…”

“…This is another limitation of our study, while patients with the use of statins, chloroquine, HQ, and lopinavir/ritonavir were not eligible in the Davoodi et al study. 28 …”

Cardiovascular drugs and COVID‐19 clinical outcomes: a systematic review and meta‐analysis of randomized controlled trials

“…length (8.0 ± 2.0 vs. 9.8 ± 2.3 d, P = .012) although it had no effect on severity (3 vs. 4 ICU admissions, P = .5); however, the trial itself was small sized (n = 40 patients) 58. 4 | DISCUSSION…”

Effects of statins on clinical outcomes in hospitalized patients with COVID-19

“…Search strategy yielded 496 potentially relevant records and six fulltext articles were assessed for eligibility. Five RCTs [2][3][4][5][6] were selected for the meta-analysis (Supplementary file) and a total of 1132 patients were included, 556 in the intervention group and 576 in the control group (placebo or standard protocol). Of the included trials, four used atorvastatin (20 mg/day [2,3] or 40 mg/day [4,5]) and one used rosuvastatin (40 mg/day) [6] as treatment for hospitalized patients with COVID-19 (Supplementary file).…”