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Erschienen in: Intensive Care Medicine 10/2014

01.10.2014 | Original

Effect of the use of low and high potency statins and sepsis outcomes

verfasst von: Shu-Yu Ou, Hsi Chu, Pei-Wen Chao, Shuo-Ming Ou, Yi-Jung Lee, Shu-Chen Kuo, Szu-Yuan Li, Chia-Jen Shih, Yung-Tai Chen

Erschienen in: Intensive Care Medicine | Ausgabe 10/2014

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Abstract

Introduction

Although statins have been shown to have cholesterol-lowering effects, their pleiotropic benefits on sepsis remain a matter of debate. In addition, the influence of statin potency on sepsis-related mortality has never been explored. The aim of our study was to determine the sepsis outcomes of low- and high-potency statin users and non-users.

Methods

This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan’s National Health Insurance program. Patients were hospitalized for sepsis between 2000 and 2010. All-cause mortality and major adverse consequences of sepsis, such as in-hospital death, intensive care unit admission, shock events, and the use of mechanical ventilation, were assessed. Patients were divided into high-potency statin users (at least 10 mg rosuvastatin, at least 20 mg atorvastatin, or at least 40 mg simvastatin), low-potency statin users (all other statin treatments), and non-users.

Results

A propensity score-matched cohort of 27,792 statin users and 27,792 non-users was included. Of 27,792 statin users, 9,785 (35.2 %) were treated with high-potency statins and 18,007 (64.8 %) were treated with low-potency statins. The 1-year mortality risk was significantly lower among both low-potency [adjusted hazard ratio (aHR) 0.89, 95 % confidence interval (CI) 0.85–0.93] and high-potency (aHR 0.80, 95 % CI 0.75–0.86) statin users compared with non-users. The risks of mortality and adverse consequences of sepsis were lower among high-potency than among low-potency statin users.

Conclusions

High-potency statin use is associated with a lower risk of sepsis-related mortality compared with low-potency statin use.
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Literatur
1.
Zurück zum Zitat Ballantyne CM, Raichlen JS, Cain VA (2008) Statin therapy alters the relationship between apolipoprotein B and low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol targets in high-risk patients: the MERCURY II (measuring effective reductions in cholesterol using rosuvastatin) trial. J Am Coll Cardiol 52:626–632PubMedCrossRef Ballantyne CM, Raichlen JS, Cain VA (2008) Statin therapy alters the relationship between apolipoprotein B and low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol targets in high-risk patients: the MERCURY II (measuring effective reductions in cholesterol using rosuvastatin) trial. J Am Coll Cardiol 52:626–632PubMedCrossRef
2.
Zurück zum Zitat Maron DJ, Fazio S, Linton MF (2000) Current perspectives on statins. Circulation 101:207–213PubMedCrossRef Maron DJ, Fazio S, Linton MF (2000) Current perspectives on statins. Circulation 101:207–213PubMedCrossRef
3.
Zurück zum Zitat John S, Schneider MP, Delles C, Jacobi J, Schmieder RE (2005) Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients. Am Heart J 149:473PubMedCrossRef John S, Schneider MP, Delles C, Jacobi J, Schmieder RE (2005) Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients. Am Heart J 149:473PubMedCrossRef
4.
Zurück zum Zitat Lahera V, Goicoechea M, de Vinuesa SG, Miana M, De las Heras N, Cachofeiro V, Luno J (2007) Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins. Curr Med Chem 14:243–248PubMedCrossRef Lahera V, Goicoechea M, de Vinuesa SG, Miana M, De las Heras N, Cachofeiro V, Luno J (2007) Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins. Curr Med Chem 14:243–248PubMedCrossRef
5.
Zurück zum Zitat Skaletz-Rorowski A, Walsh K (2003) Statin therapy and angiogenesis. Curr Opin Lipidol 14:599–603PubMedCrossRef Skaletz-Rorowski A, Walsh K (2003) Statin therapy and angiogenesis. Curr Opin Lipidol 14:599–603PubMedCrossRef
6.
Zurück zum Zitat Son JW, Koh KK, Ahn JY, Jin DK, Park GS, Kim DS, Shin EK (2003) Effects of statin on plaque stability and thrombogenicity in hypercholesterolemic patients with coronary artery disease. Int J Cardiol 88:77–82PubMedCrossRef Son JW, Koh KK, Ahn JY, Jin DK, Park GS, Kim DS, Shin EK (2003) Effects of statin on plaque stability and thrombogenicity in hypercholesterolemic patients with coronary artery disease. Int J Cardiol 88:77–82PubMedCrossRef
8.
Zurück zum Zitat Tleyjeh IM, Kashour T, Hakim FA, Zimmerman VA, Erwin PJ, Sutton AJ, Ibrahim T (2009) Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med 169:1658–1667PubMedCrossRef Tleyjeh IM, Kashour T, Hakim FA, Zimmerman VA, Erwin PJ, Sutton AJ, Ibrahim T (2009) Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med 169:1658–1667PubMedCrossRef
10.
Zurück zum Zitat Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation. Intensive Care Med 38:345–358PubMedCrossRefPubMedCentral Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation. Intensive Care Med 38:345–358PubMedCrossRefPubMedCentral
11.
Zurück zum Zitat Ando H, Takamura T, Ota T, Nagai Y, Kobayashi K (2000) Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis. J Pharmacol Exp Ther 294:1043–1046PubMed Ando H, Takamura T, Ota T, Nagai Y, Kobayashi K (2000) Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis. J Pharmacol Exp Ther 294:1043–1046PubMed
12.
Zurück zum Zitat Kopterides P, Falagas ME (2009) Statins for sepsis: a critical and updated review. Clin Microbiol Infect 15:325–334PubMedCrossRef Kopterides P, Falagas ME (2009) Statins for sepsis: a critical and updated review. Clin Microbiol Infect 15:325–334PubMedCrossRef
13.
Zurück zum Zitat Mortensen EM, Restrepo MI, Copeland LA, Pugh JA, Anzueto A, Cornell JE, Pugh MJ (2007) Impact of previous statin and angiotensin II receptor blocker use on mortality in patients hospitalized with sepsis. Pharmacotherapy 27:1619–1626PubMedCrossRef Mortensen EM, Restrepo MI, Copeland LA, Pugh JA, Anzueto A, Cornell JE, Pugh MJ (2007) Impact of previous statin and angiotensin II receptor blocker use on mortality in patients hospitalized with sepsis. Pharmacotherapy 27:1619–1626PubMedCrossRef
14.
Zurück zum Zitat Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, Howe B, Jones D, Joyce C, Kostner K, McNeil J, Nichol A, Roberts, Venkatesh B, Group AN-SI-ACT (2013) A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med 187:743–750PubMedCrossRef Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, Howe B, Jones D, Joyce C, Kostner K, McNeil J, Nichol A, Roberts, Venkatesh B, Group AN-SI-ACT (2013) A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med 187:743–750PubMedCrossRef
15.
Zurück zum Zitat Yang KC, Chien JY, Tseng WK, Hsueh PR, Yu CJ, Wu CC (2007) Statins do not improve short-term survival in an oriental population with sepsis. Am J Emerg Med 25:494–501PubMedCrossRef Yang KC, Chien JY, Tseng WK, Hsueh PR, Yu CJ, Wu CC (2007) Statins do not improve short-term survival in an oriental population with sepsis. Am J Emerg Med 25:494–501PubMedCrossRef
16.
Zurück zum Zitat Fernandez R, De Pedro VJ, Artigas A (2006) Statin therapy prior to ICU admission: protection against infection or a severity marker? Intensive Care Med 32:160–164PubMedCrossRef Fernandez R, De Pedro VJ, Artigas A (2006) Statin therapy prior to ICU admission: protection against infection or a severity marker? Intensive Care Med 32:160–164PubMedCrossRef
17.
Zurück zum Zitat Leung S, Pokharel R, Gong MN (2012) Statins and outcomes in patients with bloodstream infection: a propensity-matched analysis. Crit Care Med 40:1064–1071PubMedCrossRefPubMedCentral Leung S, Pokharel R, Gong MN (2012) Statins and outcomes in patients with bloodstream infection: a propensity-matched analysis. Crit Care Med 40:1064–1071PubMedCrossRefPubMedCentral
18.
Zurück zum Zitat Patel JM, Thickett DR, Gao F, Sapey E (2013) Statins for sepsis: distinguishing signal from the noise when designing clinical trials. Am J Respir Crit Care Med 188:874PubMedCrossRef Patel JM, Thickett DR, Gao F, Sapey E (2013) Statins for sepsis: distinguishing signal from the noise when designing clinical trials. Am J Respir Crit Care Med 188:874PubMedCrossRef
19.
20.
Zurück zum Zitat Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, Lafrance JP, Levy A, Garg AX, Ernst P, Canadian Network for Observational Drug Effect Studies (2013) Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ 346:f880PubMedCrossRef Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, Lafrance JP, Levy A, Garg AX, Ernst P, Canadian Network for Observational Drug Effect Studies (2013) Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ 346:f880PubMedCrossRef
21.
Zurück zum Zitat WHO Collaborating Center for Drugs Statistics Methodology (2003) ATC index with DDDs 2003. WHO, Oslo WHO Collaborating Center for Drugs Statistics Methodology (2003) ATC index with DDDs 2003. WHO, Oslo
22.
Zurück zum Zitat Chang WP, Liu ME, Chang WC, Yang AC, Ku YC, Pai JT, Huang HL, Tsai SJ (2013) Sleep apnea and the risk of dementia: a population-based 5-year follow-up study in Taiwan. PLoS One 8:e78655PubMedCrossRefPubMedCentral Chang WP, Liu ME, Chang WC, Yang AC, Ku YC, Pai JT, Huang HL, Tsai SJ (2013) Sleep apnea and the risk of dementia: a population-based 5-year follow-up study in Taiwan. PLoS One 8:e78655PubMedCrossRefPubMedCentral
23.
Zurück zum Zitat Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383PubMedCrossRef Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383PubMedCrossRef
24.
Zurück zum Zitat Rubin DB, Thomas N (1996) Matching using estimated propensity scores: relating theory to practice. Biometrics 52:249–264PubMedCrossRef Rubin DB, Thomas N (1996) Matching using estimated propensity scores: relating theory to practice. Biometrics 52:249–264PubMedCrossRef
25.
Zurück zum Zitat Austin PC (2008) A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat Med 27:2037–2049PubMedCrossRef Austin PC (2008) A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat Med 27:2037–2049PubMedCrossRef
26.
Zurück zum Zitat Brealey DA, Singer M, Terblanche M (2011) Potential metabolic consequences of statins in sepsis. Crit Care Med 39:1514–1520PubMedCrossRef Brealey DA, Singer M, Terblanche M (2011) Potential metabolic consequences of statins in sepsis. Crit Care Med 39:1514–1520PubMedCrossRef
27.
Zurück zum Zitat Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011: I. nephrology, epidemiology, nutrition and therapeutics, neurology, ethical and legal issues, experimentals. Intensive Care Med 38:192–209PubMedCrossRefPubMedCentral Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011: I. nephrology, epidemiology, nutrition and therapeutics, neurology, ethical and legal issues, experimentals. Intensive Care Med 38:192–209PubMedCrossRefPubMedCentral
28.
Zurück zum Zitat Martin CP, Talbert RL, Burgess DS, Peters JI (2007) Effectiveness of statins in reducing the rate of severe sepsis: a retrospective evaluation. Pharmacotherapy 27:20–26PubMedCrossRef Martin CP, Talbert RL, Burgess DS, Peters JI (2007) Effectiveness of statins in reducing the rate of severe sepsis: a retrospective evaluation. Pharmacotherapy 27:20–26PubMedCrossRef
29.
Zurück zum Zitat Dobesh PP, Klepser DG, McGuire TR, Morgan CW, Olsen KM (2009) Reduction in mortality associated with statin therapy in patients with severe sepsis. Pharmacotherapy 29:621–630PubMedCrossRef Dobesh PP, Klepser DG, McGuire TR, Morgan CW, Olsen KM (2009) Reduction in mortality associated with statin therapy in patients with severe sepsis. Pharmacotherapy 29:621–630PubMedCrossRef
30.
Zurück zum Zitat Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, Goutorbe P, Lefrant JY, Wiramus S, Jung B, Perbet S, Hernu R, Nau A, Baldesi O, Allardet-Servent J, Baumstarck K, Jouve E, Moussa M, Hraiech S, Guervilly C, Forel JM, Group S-VS (2013) Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA 310:1692–1700PubMedCrossRef Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, Goutorbe P, Lefrant JY, Wiramus S, Jung B, Perbet S, Hernu R, Nau A, Baldesi O, Allardet-Servent J, Baumstarck K, Jouve E, Moussa M, Hraiech S, Guervilly C, Forel JM, Group S-VS (2013) Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA 310:1692–1700PubMedCrossRef
31.
Zurück zum Zitat Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea. Intensive Care Med 38:542–556PubMedCrossRefPubMedCentral Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea. Intensive Care Med 38:542–556PubMedCrossRefPubMedCentral
32.
33.
Zurück zum Zitat Liu CY, Liao CH, Chen YC, Chang SC (2010) Changing epidemiology of nosocomial bloodstream infections in 11 teaching hospitals in Taiwan between 1993 and 2006. J Microbiol Immunol Infect 43:416–429PubMedCrossRef Liu CY, Liao CH, Chen YC, Chang SC (2010) Changing epidemiology of nosocomial bloodstream infections in 11 teaching hospitals in Taiwan between 1993 and 2006. J Microbiol Immunol Infect 43:416–429PubMedCrossRef
34.
Zurück zum Zitat Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A (2004) Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 110:880–885PubMedCrossRef Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A (2004) Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 110:880–885PubMedCrossRef
35.
Zurück zum Zitat Fuller BM, Gajera M, Schorr C, Gerber D, Dellinger RP, Zanotti S (2012) The association of prior statin use in septic shock treated with early goal directed therapy. Eur J Emerg Med 19:226–230PubMedCrossRefPubMedCentral Fuller BM, Gajera M, Schorr C, Gerber D, Dellinger RP, Zanotti S (2012) The association of prior statin use in septic shock treated with early goal directed therapy. Eur J Emerg Med 19:226–230PubMedCrossRefPubMedCentral
36.
Zurück zum Zitat Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C (2004) Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141:47–56PubMedCrossRef Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C (2004) Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141:47–56PubMedCrossRef
37.
Zurück zum Zitat Kruger PS, Harward ML, Jones MA, Joyce CJ, Kostner KM, Roberts MS, Venkatesh B (2011) Continuation of statin therapy in patients with presumed infection: a randomized controlled trial. Am J Respir Crit Care Med 183:774–781PubMedCrossRef Kruger PS, Harward ML, Jones MA, Joyce CJ, Kostner KM, Roberts MS, Venkatesh B (2011) Continuation of statin therapy in patients with presumed infection: a randomized controlled trial. Am J Respir Crit Care Med 183:774–781PubMedCrossRef
38.
Zurück zum Zitat Bruyere R, Vigneron C, Prin S, Pechinot A, Quenot JP, Aho S, Papazian L, Charles PE (2014) Impact of prior statin therapy on the outcome of patients with suspected ventilator-associated pneumonia: an observational study. Crit Care 18:R83PubMedCrossRefPubMedCentral Bruyere R, Vigneron C, Prin S, Pechinot A, Quenot JP, Aho S, Papazian L, Charles PE (2014) Impact of prior statin therapy on the outcome of patients with suspected ventilator-associated pneumonia: an observational study. Crit Care 18:R83PubMedCrossRefPubMedCentral
39.
Zurück zum Zitat Loppnow H, Zhang L, Buerke M, Lautenschlager M, Chen L, Frister A, Schlitt A, Luther T, Song N, Hofmann B, Rose-John S, Silber RE, Muller-Werdan U, Werdan K (2011) Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures. J Cell Mol Med 15:994–1004PubMedCrossRef Loppnow H, Zhang L, Buerke M, Lautenschlager M, Chen L, Frister A, Schlitt A, Luther T, Song N, Hofmann B, Rose-John S, Silber RE, Muller-Werdan U, Werdan K (2011) Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures. J Cell Mol Med 15:994–1004PubMedCrossRef
40.
Zurück zum Zitat Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 46:399–424CrossRef Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 46:399–424CrossRef
Metadaten
Titel
Effect of the use of low and high potency statins and sepsis outcomes
verfasst von
Shu-Yu Ou
Hsi Chu
Pei-Wen Chao
Shuo-Ming Ou
Yi-Jung Lee
Shu-Chen Kuo
Szu-Yuan Li
Chia-Jen Shih
Yung-Tai Chen
Publikationsdatum
01.10.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 10/2014
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-014-3418-1

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