Discussion
In our retrospective cohort study, among 991 patients suffering severe to criticalCOVID-19, atorvastatin which were administered for 421 of the patients was associated with a significant decrease in mortality (HR=0.679), the need for mechanical ventilation (HR=0.602), and hospital length of stay. Very little was found in the literature about the role of statins in the management of patients with COVID 19. In line with our study, data from the largest cohort study from China by Zhang et al, demonstrated that in-hospital use of statins improved survival among COVID-19 patients (HR=0.58). In this retrospective study, which included 1219 patients who used a statin, 28-day all-cause mortality risk was 5.2% and 9.4% in the statin and none statin users, respectively19. The lower mortality rate in this study compared to our results could be due to including moderate cases in the study by Zhang et al. which were not included in our study. Another study enrolled 71 patients with a pre-existing chronic cardiovascular disease, and in accordance with our findings, the mortality rate of patients who received statins was lower compared to the group of patients without statins (21.4% vs. 34.5%; p<0.05), and in their subgroup analysis, it is reported a significant reduction in mortality in the patients who were taking atorvastatin compared to non-statin users and patients who were taking other statins (P=0.025)20. In another retrospective cohort study, which compared intensive-care unit (ICU) admission, invasive mechanical ventilation rate, and death between statin users and non-statin users, ICU admission was lower in the statin group but other outcomes were not different between the two groups21. Another retrospective multicenter cohort study showed a significant association between statin intake in 31 subjects and the absence of symptoms during COVID-19 with an odds ratio of 2.91, nevertheless, there were no effects on serious clinical outcomes22.
Based on the result from our study which is in accordance with the previously performed studies, reduced need for mechanical ventilation as two important measures for pulmonary function, we could say that atorvastatin administration strongly reduces the disease severity by inhibition of the inflammatory process during the disease course. Also, these effects alongside to reduction in mortality rate which was statistically significant, make the medication an important choice of add-on therapy. Based on the significance of the mechanisms involved in the beneficial effect of the atorvastatin in the course of COVID-19, and the clinically proven efficacy, we could consider it in the treatment of patients who suffer from a severe form of the disease. It is important to note that, we studied the effect of the atorvastatin on the outcome of the patients as add-on therapy and we should not forget about the importance of early antiviral agents administration as potent inhibitors of the viral replication which could reduce the hospital length of stay23, the role of potent anti-inflammatory agents such as corticosteroids and interleukin pathways inhibitors on mortality and severity in the treatment of the COVID-19 24-27.
By considering the result of the study, we should be aware of the limitation we are facing in this study. First, this study was performed by a retrospective method which makes further randomized controlled trials emerge. Second, although we adjusted potential confounders to reduce the study results bias, it could be possible that some unmeasured factors such as prehospital used medication, the socioeconomic situation could interfere with the results. Third, we could expect that the result could be affected by the data from other institutions and a multicentric designed prospective study may be needed. Fourth, as we included data of the hospitalized patients with the severe form of the disease, extrapolation of the results to non-hospitalized patients with moderate disease severity may not be possible.