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01-05-2015 | Original

Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study

Authors: Min-Juei Tsai, Shuo-Ming Ou, Chia-Jen Shih, Pei-wen Chao, Lan-Fu Wang, Yu-Ning Shih, Szu-Yuan Li, Shu-Chen Kuo, Yen-Tao Hsu, Yung-Tai Chen

Published in: Intensive Care Medicine | Issue 5/2015

Abstract

Background

Antiplatelet agents are widely used for cardiovascular disea ses, but their pleiotropic effects in sepsis are controversial.

Objective

To investigate the association between antiplatelet agents and the survival benefit for sepsis patients.

Design

A nationwide population-based cohort and nested case–control study.

Setting

Taiwan National Health Insurance database.

Participants

All patients (age ≥18 years) who were hospitalized for sepsis between January 2000 and December 2010.

Measurements

Conditional logistic regression was used to adjust for confounding. Adjusted odd ratios (ORs) were used to compare the mortality rate due to sepsis in antiplatelet drug users and nonusers.

Results

Of 683,421 included patients, 229,792 (33.6 %) patients died during hospitalization for sepsis, and the rest (64.4 %) survived to discharge. Use of antiplatelet agents before admission was associated with a lower risk of mortality in sepsis patients (aOR 0.82, 95 % confidence interval [CI] 0.81–0.83, P < 0.001). By using another case–control study design, the beneficial effect was more significant in current users (aOR 0.78, 95 % CI 0.76–0.79) than in recent users (aOR 0.88, 95 % CI 0.85–0.91), but was not significant in past users (aOR 1.00, 95 % CI 0.98–1.02).

Limitations

Observational study.

Conclusions

Prior use of antiplatelet agents was associated with a survival benefit in sepsis patients.

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Angus DC, van der Poll T (2013) Severe sepsis and septic shock. N Engl J Med 369:840–851CrossRefPubMed

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the US: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310CrossRefPubMed

Alberti C, Brun-Buisson C, Chevret S, Antonelli M, Goodman SV, Martin C, Moreno R, Ochagavia AR, Palazzo M, Werdan K, Le Gall JR (2005) Systemic inflammatory response and progression to severe sepsis in critically ill infected patients. Am J Respir Crit Care Med 171:461–468CrossRefPubMed

Antonelli M, Bonten M, Cecconi M, Chastre J, Citerio G, Conti G, Curtis JR, Hedenstierna G, Joannidis M, Macrae D, Maggiore SM, Mancebo J, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2013) Year in review in Intensive Care Medicine 2012: I. Neurology and neurointensive care, epidemiology and nephrology, biomarkers and inflammation, nutrition, experimentals. Intensive Care Med 39:232–246CrossRefPubMedCentralPubMed

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 38:192–209CrossRefPubMedCentralPubMed

Semple JW, Italiano JE Jr, Freedman J (2011) Platelets and the immune continuum. Nat Rev Immunol 11:264–274CrossRefPubMed

Akinosoglou K, Alexopoulos D (2014) Use of antiplatelet agents in sepsis: a glimpse into the future. Thromb Res 133:131–138CrossRefPubMed

Pu Q, Wiel E, Corseaux D, Bordet R, Azrin MA, Ezekowitz MD, Lund N, Jude B, Vallet B (2001) Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endothelium in Escherichia coli endotoxin-induced shock. Crit Care Med 29:1181–1188CrossRefPubMed

Evangelista V, Manarini S, Dell’Elba G, Martelli N, Napoleone E, Di Santo A, Lorenzet PS (2005) Clopidogrel inhibits platelet–leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost 94:568–577PubMed

10.

Eisen DP, Reid D, McBryde ES (2012) Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis. Crit Care Med 40:1761–1767CrossRefPubMed

11.

Sossdorf M, Otto GP, Boettel J, Winning J, Losche W (2013) Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients. Crit Care 17:402CrossRefPubMedCentralPubMed

12.

Valerio-Rojas JC, Jaffer IJ, Kor DJ, Gajic O, Cartin-Ceba R (2013) Outcomes of severe sepsis and septic shock patients on chronic antiplatelet treatment: a historical cohort study. Crit Care Res Pract 2013:782573PubMedCentralPubMed

13.

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) 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. Chest 101:1644–1655CrossRefPubMed

14.

Chao PW, Shih CJ, Lee YJ, Tseng CM, Kuo SC, Shih YN, Chou KT, Tarng DC, Li SY, Ou SM, Chen YT (2014) Association of post discharge rehabilitation with mortality in intensive care unit survivors of sepsis. Am J Respir Crit Care Med 190:1003–1011CrossRefPubMed

15.

O’Neal HR Jr, Koyama T, Koehler EA, Siew E, Curtis BR, Fremont RD, May AK, Bernard GR, Ware LB (2011) Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome. Crit Care Med 39:1343–1350CrossRefPubMedCentralPubMed

16.

Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C (2005) Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 353:2373–2383CrossRefPubMed

17.

Price MJ, Coleman JL, Steinhubl SR, Wong GB, Cannon CP, Teirstein PS (2006) Onset and offset of platelet inhibition after high-dose clopidogrel loading and standard daily therapy measured by a point-of-care assay in healthy volunteers. Am J Cardiol 98:681–684CrossRefPubMed

18.

Gando S (2010) Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med 38:S35–S42CrossRefPubMed

19.

Winning J, Reichel J, Eisenhut Y, Hamacher J, Kohl M, Deigner HP, Claus RA, Bauer M, Losche W (2009) Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanisms. Platelets 20:50–57CrossRefPubMed

20.

Minneci PC, Deans KJ, Cui X, Banks SM, Natanson C, Eichacker PQ (2006) Antithrombotic therapies for sepsis: a need for more studies. Crit Care Med 34:538–541CrossRefPubMed

21.

Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, Munoz A (2009) Unfractioned heparin for treatment of sepsis: a randomized clinical trial (the HETRASE study). Crit Care Med 37:1185–1196CrossRefPubMed

22.

Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM (2001) Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 286:1869–1878CrossRefPubMed

23.

Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettila V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA (2003) Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 290:238–247CrossRefPubMed

24.

Gear AR, Camerini D (2003) Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 10:335–350CrossRefPubMed

25.

Totani L, Dell’Elba G, Martelli N, Di Santo A, Piccoli A, Amore C, Evangelista V (2012) Prasugrel inhibits platelet–leukocyte interaction and reduces inflammatory markers in a model of endotoxic shock in the mouse. Thromb Haemost 107:1130–1140CrossRefPubMed

26.

Garcia CC, Guabiraba R, Soriani FM, Teixeira MM (2010) The development of anti-inflammatory drugs for infectious diseases. Discov Med 10:479–488PubMed

27.

Aronoff DM (2012) Cyclooxygenase inhibition in sepsis: is there life after death? Mediators Inflamm 2012:696897PubMedCentralPubMed

28.

Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 336:912–918CrossRefPubMed

29.

Haupt MT, Jastremski MS, Clemmer TP, Metz CA, Goris GB (1991) Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. The Ibuprofen Study Group. Crit Care Med 19:1339–1347CrossRefPubMed

30.

Memis D, Karamanlioglu B, Turan A, Koyuncu O, Pamukcu Z (2004) Effects of lornoxicam on the physiology of severe sepsis. Crit Care 8:R474–R482CrossRefPubMedCentralPubMed

31.

Gambim MH, do Carmo Ade O, Marti L, Verissimo-Filho S, Lopes LR, Janiszewski M (2007) Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care 11:R107CrossRefPubMedCentralPubMed

32.

Secor D, Li F, Ellis CG, Sharpe MD, Gross PL, Wilson JX, Tyml K (2010) Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries. Intensive Care Med 36:1928–1934CrossRefPubMedCentralPubMed

33.

Rahman M, Zhang S, Chew M, Ersson A, Jeppsson B, Thorlacius H (2009) Platelet-derived CD40L (CD154) mediates neutrophil upregulation of Mac-1 and recruitment in septic lung injury. Ann Surg 250:783–790CrossRefPubMed

34.

Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P (2007) Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13:463–469CrossRefPubMed

35.

Shen HN, Lu CL, Yang HH (2010) Epidemiologic trend of severe sepsis in Taiwan from 1997 through 2006. Chest 138:298–304CrossRefPubMed

36.

Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370:1683–1693CrossRefPubMed

Title: Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study
Authors: Min-Juei Tsai
Shuo-Ming Ou
Chia-Jen Shih
Pei-wen Chao
Lan-Fu Wang
Yu-Ning Shih
Szu-Yuan Li
Shu-Chen Kuo
Yen-Tao Hsu
Yung-Tai Chen
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: Intensive Care Medicine / Issue 5/2015
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-015-3760-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study

Abstract

Background

Objective

Design

Setting

Participants

Measurements

Results

Limitations

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

Design

Setting

Participants

Measurements

Results

Limitations

Conclusions

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