Pleiotropic effects of statins in sepsis

Main Article Content

Silvana Menegoto Nogueira Di Giusto
Kelly Cristina Batista de Souto Queiroz
Rodrigo Daminello Raimundo
Luiz Carlos de Abreu
Mônica Akemi Sato

Abstract

The objective of this study was to review the effects of statin therapy in patients with signs of sepsis. A bibliographic search of articles published between 2009-2013 was performed in the MEDLINE/PubMed, SciELO and LILACS databases. Randomized controlled trials and observational clinical cohort studies were included. The results show that several clinical and observational studies have investigated the effect of statin in infection and sepsis, both pre-hospital continuous use (with or without interruption during hospitalization) or starting immediately post-hospitalization. Some studies describe positive and beneficial effects of statin therapy in the context of sepsis, including improvement on inflammatory parameters and mortality rates. However, these results do not hold on when statistic methods, which take into account different variables such as age, sex, comorbidities and severity disease, are applied. To date, no study has demonstrated strong and significant evidence regarding the reduction of morbidity and mortality in sepsis associated with the use of statin. This indicates that beneficial and protective effects have not been fully defined yet. More researches are required to confirm the results found so far.

Downloads

Download data is not yet available.

Article Details

How to Cite
Giusto, S. M. N. D., Queiroz, K. C. B. de S., Raimundo, R. D., Abreu, L. C. de, & Sato, M. A. (2014). Pleiotropic effects of statins in sepsis. ABCS Health Sciences, 39(1). https://doi.org/10.7322/abcshs.v39i1.249
Section
Review Articles

References

Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546-54. http://dx.doi.org/10.1056/NEJMoa022139

Hospital Sírio Libanês [Internet]. Diagnóstico e tratamento precoces da sepse em adulto: protocolo institucional. Disponível em: http://www.hospitalsiriolibanes.org.br/sociedade-beneficente-senhoras/Documents/protocolos-institucionais/protocolo-sepse.pdf. Acesso em: 27 jun. 2013.

Usinger J, Kazama H, McDonough JS, Griffith TS, Hotchkiss RS, Ferguson TA. Sepsis-induced apoptosis leads to active suppression of delayed-type hypersensitivity by CD8+ regulatory T cells trough a TRAIL-dependent mechanism. J Immunol. 2010;184(12):6766-72. http://dx.doi.org/10.4049/jimmunol.0904054

Remick DG. Pathophysiology of sepsis. Am J Pathol. 2007;170(5):1435-44. http://dx.doi.org/10.2353/ajpath.2007.060872

de Mendonça A, Vincent JI, Suter PM, Moreno R, Dearden NM, Antonelli M, et al. Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care Med. 2000;26(7):915-21. http://dx.doi.org/10.1007/s001340051281

Brivet FG, Kleinknecht DJ, Loirat P, Landais PJ. Acute renal failure in intensive care units: causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. French Group on Acute Renal Failure. Crit Care Med. 1996;24(2):192-8. http://dx.doi.org/10.1097/00003246-199602000-00003

Ritt LEF, Guimarães, HP, Avezum A, Piegas LS. Statins on sepsis: a new therapeutic gun in intensive care medicine? Rev Bras Ter Intensiva. 2006;18(4):402-406. http://dx.doi.org/10.1590/S0103-507X2006000400014

Williams JM, Greenslade JH, Chu K, Brown AF, Paterson D, Lipman J. Prior statin use is not associated with improved outcome in emergency patients admitted with infection: a prospective observational study. Acad Emerg Med. 2011;18(2):127-34. http://dx.doi.org/10.1111/j.1553-2712.2010.00976.x

Raetz CR. Biochemistry of endotoxins. Annu Rev Biochem. 1990;59:129-170. http://dx.doi.org/10.1146/annurev.bi.59.070190.001021

Flo TH, Halaas O, Torp S, Ryan L, Lien E, Dybdahl B, et al. Differential expression of Toll-like receptor 2 in human cells. J Leukoc Biol. 2001;69(3):474-81.

Dybdahl B, Wahba A, Lien E, Flo TH, Waage A, Qureshi N, et al. Inflammatory response after open heart surgery: release of heart-shock protein 70 and signaling through toll-like receptor-4. Circulation. 2002;105(6):685-690. http://dx.doi.org/10.1161/hc0602.103617

Schor N. Acute renal failure and the sepsis syndrome. Kidney Int. 2002;61(2):764-76. http://dx.doi.org/10.1046/j.1523-1755.2002.00178.x

Boechat AL, Boechat NO. Sepse: diagnóstico e tratamento. Rev Bras Clin Med São Paulo. 2010;8(5):420-7.

Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. 1997;112(1):235-43. http://dx.doi.org/10.1378/chest.112.1.235

Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone MA Jr. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol. 1986;136(5):1680-7.

Takemoto M, Liao JK. Pleiotropic effects of 3-hidroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arteriocler Thromb Vasc Biol. 2001;21(11):1712-9. http://dx.doi.org/10.1161/hq1101.098486

Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA. 1998;279(20):1643-50. http://dx.doi.org/10.1001/jama.279.20.1643

Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: satins as antiinflamatory agents? Circulation. 2004;109(21 Suppl 1):II18-26.

Issacsohn J, Setaro JF, Nicholas C, Davey JA, Diotalevi LJ, Christianson DS, et al. Effects of lovastatin therapy on plasminogen activator inhibitor-1 antigen levels. Am J Cardiol. 1994;74(7):735-7.

http://dx.doi.org/10.1016/0002-9149(94)90322-0

Sakamoto K, Sakamoto T, Ogawa H. The effect of 6 months of treatment with pravastatin on serum adiponection concentrations in Japanese patients with coronary artery disease and hypercholesterolemia: a pilot study. Clin Ther. 2006;28(7):1012-21. http://dx.doi.org/10.1016/j.clinthera.2006.07.001

Farmer JA. Pleiotropic effects of statins. Curr Atheroscler Rep. 2000;2(3):208-17. http://dx.doi.org/10.1007/s11883-000-0022-3

Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, et al. Measurement of C-reactive protein for the targeting of statins therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344(26):1959-65. http://dx.doi.org/10.1056/NEJM200106283442601

Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001;108(3):391-7. http://dx.doi.org/10.1172/JCI200113152

Terada Y, Inoshita S, Nakashima O, Yamada T, Kuwahara M, Sasaki S, et al. Lovastatin inhibits mesangial cell proliferation via p27Kip1. J Am Soc Nephrol. 1998;9(12):2235-43.

Sparrow CP, Burton CA, Hernandez M, Mundt S, Hassing H, Patel S, et al. Simvastatin has anti-inflamatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol. 2001;21(1):115-21. http://dx.doi.org/10.1161/01.ATV.21.1.115

Zoja C, Corna D, Rottoli D, Cattaneo D, Zanchi C, Tomasoni S, et al. Effect of combining ACE inhibitor and statin in severe experimental nephropathy. Kidney Int. 2002;61(5):1635-45. http://dx.doi.org/10.1046/j.1523-1755.2002.00332.x

Novak V, Eisinger M, Frenkel A, Terblanche M, Adhikari NK, Douvdevani A, et al. The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical Trial. Intensive Care Med. 2009;35(7):1255-60. http://dx.doi.org/10.1007/s00134-009-1429-0

Kruger PS, Harward ML, Jones MA, Joyce CJ, Kostner KM, Roberts MS, et al. Continuation of statin therapy in patients with presumed infection a randomized controlled trial. Am J Respir Crit Care Med. 2011;183(6):774-81. http://dx.doi.org/10.1164/rccm.201006-0955OC

Nseir W, Mograbi J, Abu-Elheja O, Bishara J, Assy N. The impact of prior long-term versus short-term statin use on the mortality of bacteraemic patients. Infection. 2012;40(1):41-8. http://dx.doi.org/10.1007/s15010-011-0190-9

Patel JM, Snaith C, Thickett DR, Linhartova L, Melody T, Hawkey P, et al. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Crit Care. 2012;16(6):R231. http://dx.doi.org/10.1186/cc11895

Donnino MW, Cocchi MN, Howell M, Clardy P, Talmor D, Cataldo L, et al. Statin therapy is associated with decreased mortality in patients with infection. Acad Emerg Med. 2009;16(3):230-4. http://dx.doi.org/10.1111/j.1553-2712.2009.00350.x

Mekontso Dessap A, Ouanes I, Rana N, Borghi B, Bazin C, Katsahian S, et al. Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study. Crit Care. 2011;15(4):R171. http://dx.doi.org/10.1186/cc10317

Williams JM, Greenslade JH, Chu K, Brown AF, Paterson D, Lipman J. Prior statin use is not associated with improved outcome in emergency patients admitted with infection: a prospective observational study. Acad Emerg Med. 2011;18(2):127-34. http://dx.doi.org/10.1111/j.1553-2712.2010.00976.x

. Leung S, Pokharel R, Gong MN. Statins and outcomes in patients with bloodstream infection: a propensity-matched analysis. Crit Care Med. 2012;40(4):1064-71.http://dx.doi.org/10.1097/CCM.0b013e31823bc9e7

. Knopp RH. Drug treatment of lipid disorders. N Engl J Med. 1999;341(7):498-511.

Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:(9493):1267-78.

Tolman KG. The liver and lovastatin. Am J Cardiol. 2002;89(12):1374-80. http://dx.doi.org/10.1016/S0002-9149(02)02355-X

Carrillo-Esper R, Rivera-Buendía S, Carrillo-Córdova JR, Carrillo-Córdova LD. Estatinas, ¿alternativa terapéutica en sepsis? Gac Méd Méx. 2007;143(6):499-3.