Systematic review of statins in sepsis: There is no evidence of dose response.
OBJECTIVE
Sepsis is a common cause of morbidity and mortality and is associated with significant costs to the healthcare organizations. We performed a systematic review and meta-analysis to assess whether high or low-dose statin therapy improved mortality in patients with sepsis.


METHODS
The trials analyzed in this study were multicenter or single center randomized control studies using statins for sepsis in a hospital setting. The patients included were adults with suspected or confirmed infection.


METHODS
This study found eight randomized controlled trials where participants were given either a statin or placebo daily for 14-28 days, the duration of their illness, or until their death or discharge, which ever occurred first.
This meta-analysis measured the effect of statin therapy on in hospital and 28 days mortality.


RESULTS
In unselected patients, there was no demonstrable difference in the 28 days mortality (relative risk [RR] 0.88 95% confidence interval [CI], 0.70-1.12 and P = 0.16). There was also no significant difference between statin versus placebo for in-hospital mortality (RR 0.98 95% CI, 0.85-1.14 P = 0.36). When the studies where divided into low-dose and high-dose groups, there were no statistically significant differences for in-hospital mortality between low-dose statin versus placebo for (RR 0.81 CI 0.44-1.49 P = 0.27) or high-dose statin versus placebo (RR 0.99 95% CI 0.85-1.16, P = 0.28). There was no significant difference in adverse effects between the high- and low-dose groups.


CONCLUSIONS
In this meta-analysis, we found that the use of statins did not significantly improve either in-hospital mortality or 28-day mortality in patients with sepsis. In the low-dose group, there were fewer quality multicenter studies; hence, conclusions based on the results of this subgroup are limited.
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Morgan
M
Quinn
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Claire
C
Moody
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Bill
B
Tunnicliffe
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Zahid
Z
Khan
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Mav
M
Manji
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Sandeep
S
Gudibande
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Nick
N
Murphy
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Tony
T
Whitehouse
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK.
Catherine
C
Snelson
Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK; Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK; School of Immunity and Infection, University of Birmingham, B15 2TT, UK.
Tonny
T
Veenith
High dose; low dose; mortality; sepsis; statin
JAMA. 2013 Oct 23;310(16):1692-700
24108510
Lancet. 2001 Oct 27;358(9291):1383-5
11705478
Circulation. 2005 Jul 5;112(1):117-24
15998696
Intensive Care Med. 2006 Jan;32(1):75-9
16283159
Am J Med. 2015 Apr;128(4):410-7.e1
25526798
Circulation. 2004 Aug 17;110(7):880-5
15289367
Ann Intensive Care. 2012 Jun 18;2(1):19
22709377
N Engl J Med. 2002 Apr 18;346(16):1221-31
11961152
Arch Intern Med. 1991 Jan;151(1):43-9
1985608
Crit Care. 2012 Dec 11;16(6):R231
23232151
NCHS Data Brief. 2011 Jun;(62):1-8
22142805
N Engl J Med. 2014 Jun 5;370(23):2191-200
24835849
Crit Care Med. 2006 Feb;34(2):344-53
16424713
Lancet Infect Dis. 2007 May;7(5):358-68
17448939
Lancet Infect Dis. 2006 Apr;6(4):242-8
16554249
Am J Respir Crit Care Med. 2011 Mar 15;183(6):774-81
20959555
Intensive Care Med. 2009 Jul;35(7):1255-60
19205663
Am J Respir Crit Care Med. 2013 Apr 1;187(7):743-50
23348980
Am J Cardiol. 2003 Jul 15;92(2):152-60
12860216
Ann Pharmacother. 1995 Jul-Aug;29(7-8):743-59
8520093
N Engl J Med. 2014 Oct 30;371(18):1695-703
25268516
Am J Respir Crit Care Med. 2011 Mar 1;183(5):620-6
20870757
Trends Immunol. 2007 Feb;28(2):88-98
17197237
Lancet Infect Dis. 2007 Feb;7(2):80; author reply 80-1
17251076
Annu Rev Pharmacol Toxicol. 2005;45:89-118
15822172