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Statins and outcomes of hospitalized patients with laboratory-confirmed 2017–2018 influenza

  • Alaa AtamnaEmail author
  • Tanya Babitch
  • Mayaan Bracha
  • Nadav Sorek
  • Ben-Zvi Haim
  • Avishay Elis
  • Jihad Bishara
  • Tomer Avni
Original Article
  • 70 Downloads

Abstract

No studies evaluating the association between statins and outcomes of patients with seasonal influenza have been performed since the 2007–2008 and the 2009 pandemic H1N1 influenza seasons. All consecutive hospitalized patients between October 2017 and April 2018, diagnosed with laboratory-confirmed influenza A and B virus, were included. Patients were divided into two groups: statin and non-statin users. Outcomes were 30- and 90-day mortality, complications (pneumonia, myocarditis, encephalitis, intensive care unit (ICU) transfer, mechanical ventilation, vasopressor support), length of hospital stay, and readmission rates. A multivariate analysis was performed to adjust for mortality risk factors. To compare the groups, we matched patients to the nearest neighbor propensity score. Of the 526 patients ill with influenza A (201/526) and B (325/526), 36% (188/526) were statin users; 64% (338/526) were not. Statin users were older (78 vs.70; p = < 0.05) and suffered from more comorbidities (Charlson comorbidity scores of 6 vs.4; p < 0.005). The 30-day mortality rate among statin vs. non-statin users was 6% vs. 8% (p = 0.3). On multivariate analysis, statin use was not associated with mortality benefit (OR = 0.67 (0.29–1.36)). After propensity score matching, the results were unchanged (OR = 0.71 (0.29–1.71)). Statin users were diagnosed with less complicated diseases as they were less likely to receive vasopressor support, mechanical ventilation, and/or transfer to the ICU. Although statin users were significantly older and exhibited more comorbidities, 30-day mortality rates did not differ between statin users and non-users, which may signify a protective role of statins on seasonal influenza patients. Further studies performed during different influenza seasons and different subtypes are essential.

Keywords

Statins Influenza Mortality Outcomes 

Notes

Contributors

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Alaa Atamna, Tanya Babich, and Mayaan Bracha. The first draft of the manuscript was written by Alaa Atamna and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee of the Rabin Medical Center, Petah Tikva, Israel, RMC-18-0297) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was waived because of the retrospective, non-interventional nature of the study.

References

  1. 1.
    Centers for Disease Control and Prevention (2010) Estimates of deaths associated with seasonal influenza - United States, 1976-2007. MMWR 59:1057–1062Google Scholar
  2. 2.
    Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM (2009) Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. NEJM 361:1945–1952.  https://doi.org/10.1056/NEJMoa0906453 CrossRefPubMedGoogle Scholar
  3. 3.
    Reichert TA, Simonsen L, Sharma A, Pardo SA, Fedson DS, Miller MA (2004) Influenza and the winter increase in mortality in the United States, 1959-1999. Am J Epidemiol 160:492–502.  https://doi.org/10.1093/aje/kwh227 CrossRefPubMedGoogle Scholar
  4. 4.
    Simonsen L, Clarke MJ, Williamson GD, Stroup DF, Arden NH, Schonberger LB (1997) The impact of influenza epidemics on mortality: introducing a severity index. Am J Public Health 87:1944–1950.  https://doi.org/10.2105/ajph.87.12.1944 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chaves SS, Aragon D, Bennett N, Cooper T, D’Mello T, Farley M, Fowler B, Hancock E, Kirley PD, Lynfield R, Ryan P, Schaffner W, Sharangpani R, Tengelsen L, Thomas A, Thurston D, Williams J, Yousey-Hindes K, Zansky S, Finelli L (2013) Patients hospitalized with laboratory-confirmed influenza during the 2010-2011 influenza season: exploring disease severity by virus type and subtype. J Infect Dis 208:1305–1314.  https://doi.org/10.1093/infdis/jit316 CrossRefPubMedGoogle Scholar
  6. 6.
    Hernan MA, Lipsitch M (2011) Oseltamivir and risk of lower respiratory tract complications in patients with flu symptoms: a meta-analysis of eleven randomized clinical trials. Clin Infect Dis 53:277–279.  https://doi.org/10.1093/cid/cir400 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lee N, Choi KW, Chan PK, Hui DS, Lui GC, Wong BC, Wog RY, Sin WY, Hui WM, Ngai KL, Cockram CS, Lai RW, Sung JJ (2010) Outcomes of adults hospitalised with severe influenza. Thorax 65:510–515.  https://doi.org/10.1136/thx.2009.130799 CrossRefPubMedGoogle Scholar
  8. 8.
    Louie JK, Yang S, Acosta M, Yen C, Samuel MC, Schechter R, Guevara H, Uyeki TM (2012) Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1) pdm09. Clin Infect Dis 55:1198–1204.  https://doi.org/10.1093/cid/cis636 CrossRefPubMedGoogle Scholar
  9. 9.
    McGeer A, Green KA, Plevneshi A, Shigayeva A, Siddiqi N, Raboud J, Low DE, Toronto Invasive Bacterial Diseases Network (2007) Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 45:1568–1575.  https://doi.org/10.1086/523584 CrossRefPubMedGoogle Scholar
  10. 10.
    Muthuri SG, Myles PR, Venkatesan S, Leonardi-Bee J, Nguyen-Van-Tam JS (2013) Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-2010 influenza A (H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients. J Infect Dis 207:553–653.  https://doi.org/10.1093/infdis/jis726 CrossRefPubMedGoogle Scholar
  11. 11.
    Laidler MR, Thomas A, Baumbach J, Kirley PD, Meek J, Aragon D, Morin C, Ryan PA, Schaffner W, Zansky SM, Chaves SS (2015) Statin treatment and mortality: propensity score-matched analyses of 2007-2008 and 2009-2010 laboratory-confirmed influenza hospitalizations. Open Forum Infect Dis 2:ofv028.  https://doi.org/10.1093/ofid/ofv028 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Brassard P, Wu JW, Ernst P, Dell'Aniello S, Smiechowski B, Suissa S (2017) The effect of statins on influenza-like illness morbidity and mortality. Pharmacoepidemiol Drug Saf 26:63–70.  https://doi.org/10.1002/pds.4112 CrossRefPubMedGoogle Scholar
  13. 13.
    Falagas ME, Makris GC, Matthaiou DK, Rafailidis PI (2008) Statins for infection and sepsis: a systematic review of the clinical evidence. J Antimicrob Chemother 61:774–785.  https://doi.org/10.1093/jac/dkn019 CrossRefGoogle Scholar
  14. 14.
    Fedson DS (2006) Pandemic influenza: a potential role for statins in treatment and prophylaxis. Clin Infect Dis 43:199–205.  https://doi.org/10.1086/505116 CrossRefPubMedGoogle Scholar
  15. 15.
    Fedson DS (2014) How will physicians respond to the next influenza pandemic? Clin Infect Dis 58:233–237.  https://doi.org/10.1093/cid/cit695 CrossRefPubMedGoogle Scholar
  16. 16.
    Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4:977–987.  https://doi.org/10.1038/nrd1901 CrossRefPubMedGoogle Scholar
  17. 17.
    Ma Y, Wen X, Peng J, Lu Y, Guo Z, Lu J (2012) Systematic review and meta-analysis on the association between outpatient statins use and infectious disease-related mortality. PLoS One 7(12):e51548.  https://doi.org/10.1371/journal.pone.0051548 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, Farley MM, Ryan P, Lynfield R, Baumbach J, Schaffner W, Bennett N, Zansky S (2012) Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis 205:13–19.  https://doi.org/10.1093/infdis/jir695 CrossRefPubMedGoogle Scholar
  19. 19.
    Viasus D, Pano-Pardo JR, Cordero E, Campins A, Lopez-Medrano F, Villoslada A, Farinas MC, Moreno A, Rodriguez-Bano J, Oteo JA, Martinez-Montauti J, Torre-Cisneros J, Seguar F, Arratala J, Novel Influenza A (H1N1) Study Group, Spanish Network for Research in Infectious Diseases (2011) Effect of immunomodulatory therapies in patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia. J Inf Secur 62:193–199.  https://doi.org/10.1016/j.jinf.2011.01.014 CrossRefGoogle Scholar
  20. 20.
    Rothberg MB, Bigelow C, Pekow PS, Lindenauer PK (2012) Association between statins given in hospital and mortality in pneumonia patients. J Gen Intern Med 27:280–286.  https://doi.org/10.1007/s11606-011-1826-223.2 CrossRefPubMedGoogle Scholar
  21. 21.
    Nseir W, Bishara J, Mograbi J, Mahamid M, Khalaila W, Taha M, Farah R (2013) Do statins protect against the development of Clostridium difficile-associated diarrhea? J Antimicrob Chemother 68:1889–1893.  https://doi.org/10.1093/jac/dkt101 CrossRefPubMedGoogle Scholar
  22. 22.
    Nseir W, Mograbi J, Abu-Elheja O, Bishara J, Assy N (2011) The impact of long-term versus short-term statin use on the mortality of bacteraemic patients. Infection 40:41–48.  https://doi.org/10.1007/s15010-011-0190-9 CrossRefPubMedGoogle Scholar
  23. 23.
    Falagas ME, Markis GC, Mathaiou DK, Rafailidis PI (2008) Statin for infection and sepsis: a systemic review of the clinical evidence. J. Antimicrob Chemother 61:774–785.  https://doi.org/10.1093/jac/dkn019 CrossRefGoogle Scholar
  24. 24.
    Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343:425–430.  https://doi.org/10.1038/343425a0 CrossRefGoogle Scholar
  25. 25.
    Kwong JC, Li P, Redelmeier DA (2009) Influenza morbidity and mortality in elderly patients receiving statins: a cohort study. PLoS One 4:e8087.  https://doi.org/10.1371/journal.pone.0008087 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Frost FJ, Petersen H, Tollestrup K, Skipper B Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest 131:1006–1012.  https://doi.org/10.1378/chest.06-1997 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Infectious Disease Unit, Rabin Medical CenterBeilinson HospitalPetah TikvaIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Internal Medicine Department E, Rabin Medical CenterBeilinson HospitalPetah TikvaIsrael
  4. 4.Clinical Microbiology Laboratory, Rabin Medical CenterBeilinson HospitalPetah TikvaIsrael
  5. 5.Internal Medicine Department C, Rabin Medical CenterBeilinson HospitalPetah TikvaIsrael

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