A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis

Peter S Kruger, Michael John Bailey, Rinaldo Bellomo, David James Cooper, Meg Harward, Alisa Higgins, Belinda Duval Howe, Daryl Andrew Jones, Chris Joyce, Karam Kostner, John James McNeil, Alistair Dualta Nichol, Michael S Roberts, Gillian Ann Syres, Balasubramanian Venkatesh

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144 Citations (Scopus)

Abstract

Rationale: Observational studies link statin therapy with improved outcomes in patients with severe sepsis. 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 matched placebo. 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.
Original languageEnglish
Pages (from-to)743 - 750
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume187
Issue number7
DOIs
Publication statusPublished - 2013

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