Document Detail


A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis.
MedLine Citation:
PMID:  23348980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12607000028404).
Authors:
Peter Kruger; Michael Bailey; Rinaldo Bellomo; David James Cooper; Meg Harward; Alisa Higgins; Belinda Howe; Darryl Jones; Chris Joyce; Karam Kostner; John McNeil; Alistair Nichol; Michael S Roberts; Gillian Syres; Bala Venkatesh;
Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  187     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-21     Revised Date:  2013-11-11    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  743-50     Citation Subset:  AIM; IM    
Affiliation:
Intensive Care Unit, Princess Alexandra Hospital, Wooloongabba, Brisbane, Australia.
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MeSH Terms
Descriptor/Qualifier:
Aged
C-Reactive Protein / analysis
Critical Illness
Double-Blind Method
Female
Heptanoic Acids / therapeutic use*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Intensive Care Units
Interleukin-6 / blood*
Length of Stay
Lipids / blood
Male
Middle Aged
Prospective Studies
Pyrroles / therapeutic use*
Sepsis / blood,  drug therapy*,  mortality
Chemical
Reg. No./Substance:
0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Interleukin-6; 0/Lipids; 0/Pyrroles; 9007-41-4/C-Reactive Protein; A0JWA85V8F/atorvastatin
Investigator
Investigator/Affiliation:
V Bennett / ; J Board / ; D J Cooper / ; S Vallance / ; C McArthur / ; L Newby / ; C Simmonds / ; R Bellomo / ; G Eastwood / ; D Goldsmith / ; L Peck / ; C Boschert / ; J Edington / ; J Fletcher / ; G Koch / ; J Smith / ; S Arora / ; B O'Bree / ; K Shepard / ; A Bersten / ; E Matheson / ; S Allsop / ; J Botha / ; J Vuat / ; A Bone / ; T Elderkin / ; M Fraser / ; N Orford / ; T Salerno / ; K Ryan / ; T Sandford / ; J Walsham / ; K Gregory / ; T J Morgan / ; J J Presneill / ; J Sutton / ; A Tilsley / ; J Tai / ; T Williams / ; P Galt / ; M Reilly / ; C Walker / ; A Buckley / ; P Garrett / ; S McDonald / ; M Harwood / ; J Helyar / ; P Kruger / ; S Peake / ; P Williams / ; J Davis / ; D Stephens / ; J Thomas / ; R McAllister / ; A Turner / ; D Barge / ; T Caf / ; N Harley / ; H Buhr / ; D Gattas / ; D Rajbhandari / ; Charles Gardiner / ; S Baker / ; B Roberts / ; R Silcock / ; B Venkatesh /
Comments/Corrections
Comment In:
Am J Respir Crit Care Med. 2013 Oct 1;188(7):874   [PMID:  24083863 ]
Am J Respir Crit Care Med. 2013 Oct 1;188(7):874-5   [PMID:  24083864 ]
Am J Respir Crit Care Med. 2013 Apr 1;187(7):672-4   [PMID:  23540874 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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