title: Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.
abstract: BACKGROUND
  Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.
  
  
  METHODS
  We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.
  
  
  RESULTS
  Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.
  
  
  CONCLUSIONS
  Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
authors.affiliation: AP-HP, Groupe Henri-Mondor Albert-Chenevier, Service de Reanimation Medicale, 51 avenue du Mal de Lattre de Tassigny Creteil, F-94010 France. armand.dessap@hmn.aphp.fr
authors.forename: Armand
authors.initials: A
authors.lastname: Mekontso Dessap
authors.forename: Islem
authors.initials: I
authors.lastname: Ouanes
authors.forename: Nerlep
authors.initials: N
authors.lastname: Rana
authors.forename: Beatrice
authors.initials: B
authors.lastname: Borghi
authors.forename: Christophe
authors.initials: C
authors.lastname: Bazin
authors.forename: Sandrine
authors.initials: S
authors.lastname: Katsahian
authors.forename: Anne
authors.initials: A
authors.lastname: Hulin
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003657:Decision Making; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors