Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome*

Objectives: To determine whether prehospital statin use is associated with a lower risk of sepsis, acute lung injury/acute respiratory distress syndrome, and mortality in critically ill patients. We also investigated the effect of combined prehospital use of both statins and aspirin. Design: Cross-sectional analysis of a prospective cohort. Patients: A total of 575 critically ill patients admitted to the medical or surgical intensive care unit of an academic tertiary-care hospital. Interventions: None. Measurements and Main Results: Of 575 patients, 149 (26%) were on statin therapy before hospitalization. A multivariable analysis including age, gender, current tobacco use, prehospital aspirin use, race, and Acute Physiology and Chronic Health Evaluation II score revealed that patients on statin therapy before hospitalization were less likely to have or develop severe sepsis (odds ratio 0.62, 95% confidence interval 0.40–0.96) or acute lung injury/acute respiratory distress syndrome (odds ratio 0.60, 95% confidence interval 0.36–0.99) during the first four intensive care unit days. In-hospital mortalities for patients with and without prehospital statin use (odds ratio 1.06, 95% confidence interval 0.62–1.83) were similar. Patients who had prehospital use of both statins and aspirin had the lowest rates of severe sepsis, acute lung injury/acute respiratory distress syndrome, and mortality. Conclusions: Prehospital use of statins may be protective against sepsis and acute lung injury. This effect may be potentiated by prehospital aspirin use.

[1]  Anders Larsson,et al.  Preadmission statin use and one-year mortality among patients in intensive care - A cohort study , 2010, Critical care.

[2]  M. Matthay,et al.  Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. , 2009, The Journal of clinical investigation.

[3]  Lung.  Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome , 2009 .

[4]  E. Benjamin,et al.  ACCF/AHA 2009 performance measures for primary prevention of cardiovascular disease in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for Primary Prevention of Cardiova , 2009, Journal of the American College of Cardiology.

[5]  P. Libby,et al.  A randomized trial of rosuvastatin in the prevention of venous thromboembolism. , 2009, The New England journal of medicine.

[6]  M. Asaduzzaman,et al.  Platelets support pulmonary recruitment of neutrophils in abdominal sepsis* , 2009, Critical care medicine.

[7]  V. Novack,et al.  The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial , 2009, Intensive Care Medicine.

[8]  A. Weyrich,et al.  Amicus or adversary: platelets in lung biology, acute injury, and inflammation. , 2009, American journal of respiratory cell and molecular biology.

[9]  O. Gajic,et al.  Statin administration did not influence the progression of lung injury or associated organ failures in a cohort of patients with acute lung injury , 2009, Intensive Care Medicine.

[10]  Steffen Christensen,et al.  Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. , 2008, Archives of internal medicine.

[11]  Yaniv Almog,et al.  The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases* , 2007, Critical care medicine.

[12]  P. Kovanen,et al.  Protective effects of simvastatin on coronary artery function in swine with acute infection. , 2006, Atherosclerosis.

[13]  M. Pfeffer,et al.  AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. , 2006, Journal of the American College of Cardiology.

[14]  Ping Li,et al.  Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis , 2006, The Lancet.

[15]  A. Pirat,et al.  Pretreatment with Simvastatin Reduces Lung Injury Related to Intestinal Ischemia-Reperfusion in Rats , 2006, Anesthesia and analgesia.

[16]  Diane P. Martin,et al.  Incidence and outcomes of acute lung injury. , 2005, The New England journal of medicine.

[17]  D. Grigoryev,et al.  Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[18]  J. Olsen,et al.  Cancer risk among statin users: A population‐based cohort study , 2005, International journal of cancer.

[19]  M. Wolzt,et al.  Simvastatin Blunts Endotoxin-Induced Tissue Factor In Vivo , 2005, Circulation.

[20]  K. Mann,et al.  Statins and Blood Coagulation , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[21]  V. Novack,et al.  Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis , 2004, Circulation.

[22]  A. Gotto,et al.  Update on Statins: 2003 , 2004, Circulation.

[23]  R. Madhok,et al.  Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial , 2004, The Lancet.

[24]  Henk-Jan Guchelaar,et al.  The risk of cancer in users of statins. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  J. Deanfield,et al.  Beyond the Laboratory: Clinical Implications for Statin Pleiotropy , 2004, Circulation.

[26]  V. Durkalski,et al.  Oral simvastatin treatment in relapsing-remitting multiple sclerosis , 2004, The Lancet.

[27]  B. Naidu,et al.  Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion. , 2003, The Journal of thoracic and cardiovascular surgery.

[28]  R. Hotchkiss,et al.  The pathophysiology and treatment of sepsis. , 2003, The New England journal of medicine.

[29]  W. Seeger,et al.  Simvastatin Inhibits Inflammatory Properties of Staphylococcus aureus &agr;-Toxin , 2002, Circulation.

[30]  AndrewJ. S. Coats.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[31]  Arthur S Slutsky,et al.  Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome , 2002, Critical care medicine.

[32]  J. Pugin,et al.  Cytokine balance in the lungs of patients with acute respiratory distress syndrome. , 2001, American journal of respiratory and critical care medicine.

[33]  A. Szczeklik,et al.  Antithrombotic actions of statins. , 2001, Medical science monitor : international medical journal of experimental and clinical research.

[34]  A. Liappis,et al.  The effect of statins on mortality in patients with bacteremia. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[35]  N Rifai,et al.  Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. , 2001, JAMA.

[36]  J. Deisenhofer,et al.  Structural Mechanism for Statin Inhibition of HMG-CoA Reductase , 2001, Science.

[37]  D. Bouchier-Hayes,et al.  Pravastatin attenuates lower torso ischaemia-reperfusion-induced lung injury by upregulating constitutive endothelial nitric oxide synthase. , 2001, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[38]  J Ean,et al.  Efficacy and safety of recombinant human activated protein C for severe sepsis. , 2001, The New England journal of medicine.

[39]  T. Takamura,et al.  Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis. , 2000, The Journal of pharmacology and experimental therapeutics.

[40]  D. Schoenfeld,et al.  Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. , 2000, The New England journal of medicine.

[41]  A. M. Lefer,et al.  Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[42]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[43]  G. Bernard.  The Brussels Score , 1997 .

[44]  J. Heffner.  Platelet-neutrophil interactions in sepsis – platelet guilt by association? , 1997, Intensive Care Medicine.

[45]  G. Bernard,et al.  The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. , 1997, The New England journal of medicine.

[46]  B. Davis,et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. , 1996, The New England journal of medicine.

[47]  J. Carlet,et al.  INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. , 1996, Critical care medicine.

[48]  M. Lamy,et al.  The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. , 1994, American journal of respiratory and critical care medicine.

[49]  J. Heffner,et al.  The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders? , 1987, The American review of respiratory disease.

[50]  T L Petty,et al.  Acute respiratory distress in adults. , 1967, Lancet.

[51]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992. , 2009, Chest.

[52]  R. Hyzy,et al.  Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. , 2006, The New England journal of medicine.

[53]  Mark Jones,et al.  Statin therapy is associated with fewer deaths in patients with bacteraemia , 2005, Intensive Care Medicine.

[54]  S. Yusuf.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Commentary , 2002 .

[55]  Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network. , 2000, JAMA.