title: Association between statin therapy and outcomes in critically ill patients: a nested cohort study.
abstract: BACKGROUND
  The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.
  
  
  METHODS
  This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.
  
  
  RESULTS
  Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤ 100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤ 9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥ 40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.
  
  
  CONCLUSIONS
  Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.
authors.affiliation: Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Shmeylan A
authors.initials: SA
authors.lastname: Al Harbi
authors.forename: Hani M
authors.initials: HM
authors.lastname: Tamim
authors.forename: Yaseen M
authors.initials: YM
authors.lastname: Arabi
mesh_terms: D018806:APACHE; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007362:Intensive Care Units; D007902:Length of Stay; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012121:Respiration, Artificial / Q000379:methods; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology; D018805:Sepsis / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors