Statins and Risk of Thrombosis in Critically ill Patients with COVID-19: A Multicenter Cohort Study

Abstract

Purpose Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. Methods A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. Results A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. Conclusion The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.

Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study

“…This study was carried out under the auspices of the Saudi Critical Care Pharmacy Research (SCAPE) platform, which also conducted other investigations to evaluate the safety and effectiveness of various therapies in critically ill patients ( SCAPE, n.d. ). The methodology of this multicenter cohort study is comparable to other studies executed by the SCAPE platform and previously reported ( Al Harbi et al, 2022 , Al Sulaiman et al, 2022b , Al Sulaiman et al, 2022a , Al Sulaiman et al, 2021a , Al Sulaiman et al, 2021b , Aljuhani et al, 2021 ). The supplemental material contains additional details on the study's design.…”

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

“…In 2021, an observational study by Belgian investigators reported that inpatient statin treatment was associated with reduced COVID-19 mortality [ 26 ]. 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 ].…”

“…Many observational studies have reported that outpatient statins reduce COVID-19 hospitalizations and mortality [ 157 ]. These findings also apply to patients with coagulopathies and immunothrombosis [ 158 ] and risk conditions such as diabetes [ 159 ].…”

“…Of the 22 observational studies of inpatient statin treatment, 12 used propensity score matching to minimize confounding [ 26 , 158 , 182 , 185 , 187 , 189 , 191 , 193 , 194 , 196 , 197 , 205 ], five reported treating >1000 patients [ 170 , 182 , 184 , 189 , 197 ], and many of the remaining studies included hundreds of subjects. All but one observational study [ 194 ] showed that statins significantly reduced COVID-19 mortality.…”

Statin Therapy to Improve Outcome of COVID-19 Patients: Useful or Not Useful?

“…Improved survival was also found in the critically ill COVID-19 patients with a reduction in in-hospital (HR, 0.69; 95% CI, 0.54–0.89; p = 0.004) and 30-day mortality (HR, 0.75; 95% CI, 0.58–0.98; p = 0.03) [ 31 ]. However, statins did not modify the risk of thrombosis and venous thromboembolism despite the observed benefits on survival [ 32 ]. Additionally, in some studies, benefits on the different outcomes were dissociated, such as in the nationwide Swedish cohort study including 572,695 individuals, which showed a decreased risk of death (HR, 0.86; 95% CI, 0.79–0.95; p < 0.001) but not of ICU admission [ 33 ].…”