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

Kruger, Peter, Bailey, Michael, Bellomo, Rinaldo, Cooper, David James, Harward, Meg, Higgins, Alisa, Howe, Belinda, Jones, Darryl, Joyce, Chris, Kostner, Karam, McNeil, John, Nichol, Alistair, Roberts, Michael S., Syres, Gillian, Venkatesh, Bala and ANZ-STATInS Investigators–ANZICS Clinical Trials Group (2013) A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. American Journal of Respiratory and Critical Care Medicine, 187 7: 743-750. doi:10.1164/rccm.201209-1718OC

Author Kruger, Peter
Bailey, Michael
Bellomo, Rinaldo
Cooper, David James
Harward, Meg
Higgins, Alisa
Howe, Belinda
Jones, Darryl
Joyce, Chris
Kostner, Karam
McNeil, John
Nichol, Alistair
Roberts, Michael S.
Syres, Gillian
Venkatesh, Bala
ANZ-STATInS Investigators–ANZICS Clinical Trials Group
Total Author Count Override 15
Title A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis
Journal name American Journal of Respiratory and Critical Care Medicine   Check publisher's open access policy
ISSN 1073-449X
Publication date 2013-04-01
Year available 2013
Sub-type Article (original research)
DOI 10.1164/rccm.201209-1718OC
Open Access Status DOI
Volume 187
Issue 7
Start page 743
End page 750
Total pages 8
Place of publication New York, United States
Publisher American Thoracic Society
Collection year 2014
Language eng
Formatted abstract
Rationale: Observational studies link statin therapy with improved outcomes in patients with severe sepsis.

Objectives: To test whether atorvastatin therapy affects biologic 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 Sequential Organ Failure Assessment scores or mortality at intensive care unit discharge, hospital discharge, 28- or 90-day (15% vs. 19%), or adverse effects between the two groups. Cholesterol was lower in patients treated with atorvastatin (2.4 [0.07] vs. 2.6 [0.06] mmol/L; P = 0.006). In the predefined group of 77 prior statin users, those randomized to placebo had a greater 28-day mortality (28% vs. 5%; P = 0.01) compared with 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.
Keyword Statin
3-hydroxy-3-methylglutaryl CoA reductase inhibitor
Critical illness
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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