The use of statins appears to be associated with a lower mortality risk and a lower incidence of mechanical ventilation in patients hospitalised with coronavirus disease 2019 (COVID-19), according to a study published in Cell Metabolism.
The large-scale retrospective study also showed that mortality risk and other negative outcomes were not increased by combination therapy consisting of statins and angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
“These data provide supportive evidence for the safety of statin or combination of a statin with ACE inhibitors/ARBs for treatment in patients with COVID-19,” Xiao-Jing Zhang, Wuhan University, Wuhan, China, and colleagues wrote. They added that these findings “give support for the completion of on-going prospective studies and randomised controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.”
For the study, the research retrospectively analysed data from 13,981 patients with COVID-19 admitted to 21 hospitals in the Hubei Province of China. Of the patients, 1,219 received statins, primarily atorvastatin. Among patients with hypertension, 319 received statins and an ACE inhibitor or ARB, and 603 used statins combined with other antihypertensive drugs.
The risk for 28-day all-cause mortality was 5.2% among patients who received statins and 9.4% in patients who did not. Statin use was also associated with lower levels of certain inflammation biomarkers and a lower incidence of acute respiratory distress syndrome and admission to intensive care units.
Among patients with hypertension, the incidence of 28-day mortality was 0.16 cases per 100 person-days versus 0.26 per 100 person-days in the statin with ACE inhibitor/ARB group and the statin with non-ACE inhibitor/ARB group, respectively, with the IRR of 0.62 (95% CI, 0.34-1.14; P = 0.119). Using a Cox model with statin and ACE inhibitor/ARB as time-varying exposures, the authors noted there was no significant association between ACE inhibitor/ARB therapy and 28-day mortality in individuals with hypertension and statin treatment (aHR, 0.48; 95% CI, 0.21-1.07; P = 0.074).
“Although the use of an ACE inhibitor or ARB was once speculated to be potentially harmful in patients with COVID-19, numerous observational studies have shown either a protective or neutral effect on mortality,” the authors noted. “Several professional societies have recommended the continuation use of ACE inhibitors and ARBs in patients with COVID-19 and pre-existing hypertension,” they added.
“To our knowledge, the results from this study were the first clinical evidence [that] supports the notion that the risk of COVID-19 mortality was not increased by using ACE inhibitors or ARB in combination with statin treatment in individuals with COVID-19,” the authors wrote.
The authors cited the inherent limitation of a retrospective study, making it impossible to infer causality in the association between the use of statins and ACE inhibitor/ARB and the ameliorated severity and mortality in COVID-19. Moreover, they also noted that “some unforeseen confounders (e.g., prehospital medication and socioeconomic status) may still potentially alter the magnitude of statin effects on all-cause mortality of COVID-19” although multiple statistical models were used to adjust for potential bias and a sensitivity analysis was performed to show that the overall unmeasured confounders were unlikely to undermine the study’s main conclusion.