Rationale: Observational studies link statin therapy with improved outcomes in patients with
Objectives: To test whether atorvastatin therapy affects biological and clinical outcomes in
critically ill patients with severe sepsis.
Methods: Phase II, multicenter, prospective, randomized, double-blind, placebo controlled
trial stratified by site and prior statin use. A cohort of 250 critically ill patients (123 statins,
127 placebo) with severe sepsis were administrated either atorvastatin (20 mg daily) or
Measurements and Main Results: There was no difference in IL-6 concentrations (primary
end point) between the atorvastatin and placebo groups (p=0.76) and no interaction between
treatment group and time to suggest that the groups behaved differently over time (p= 0.26).
Baseline plasma IL-6, was lower among previous statin users [129(87-191) vs. 244 (187-317)
pg/ml, p=0.01]. There was no difference in length of stay, change in SOFA scores or
mortality at ICU discharge, hospital discharge, 28 days or 90 days (15 vs. 19 ) or adverse
effects between the two groups. Cholesterol was lower in atorvastatin treated patients
[2.4(0.07) vs. 2.6(0.06) mmol/L, p=0.006]. In the pre ?defined group of 77 prior statin users,
those randomised to placebo had a greater 28 day mortality (28 vs.5 , P=0.01) compared to
those who received atorvastatin. The difference was not statistically significant at 90 days (28
vs. 11 , p=0.06)
Conclusions: Atorvastatin therapy in severe sepsis did not affect IL-6 levels. Prior statin use
was associated with a lower baseline IL-6 concentration and continuation of atorvastatin in
this cohort was associated with improved survival.