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Statins and associated risk of pneumonia: a systematic review and meta-analysis of observational studies

European Journal of Clinical Pharmacology volume 68, pages 747–755 (2012)Cite this article

Abstract

Purpose

Statins have potential anti-inflammatory effects, but the association between statin use and lower incidence of pneumonia is unclear. We have therefore performed a systematic review on the risk of pneumonia in statin users versus non-users.

Methods

MEDLINE and EMBASE were searched in December 2010 for controlled observational studies that reported on the risk of pneumonia in statin users. We performed a random effects meta-analysis and assessed heterogeneity using the I2 statistic.

Results

A total of 451 citations were screened, and ultimately nine studies (4 case–control, 4 retrospective cohort, 1 prospective cohort) with more than 3 million participants were included in the meta-analysis. Pooled analysis of seven studies that reported unadjusted data failed to show a significantly reduced risk of pneumonia [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.84–1.06, p = 0.33, I2 = 79%] in statin users as compared to non-users. However, a significant reduction in the likelihood of pneumonia associated with statin use (n = 8 studies, OR 0.85, 95% CI 0.75–0.97, p = 0.02, I2 = 81%) was found in the meta-analysis of adjusted data. Both analyses were limited by substantial statistical heterogeneity. Sensitivity analysis failed to fully clarify the source of heterogeneity, but cohort studies seemed to be less heterogenous (n = 5 studies, OR 0.92, 95% CI 0.84–1.01, I2 = 43%).

Conclusion

Our findings indicate that the purported benefit of statins in preventing pneumonia is inconsistent, and of low magnitude, with upper bounds of the confidence interval being close to null. In view of the substantial statistical and clinical heterogeneity in the dataset, there is no convincing evidence to support the therapeutic application of statins for reducing the risk of pneumonia.

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References

  1. Chalmers JD, Short PM, Mandal P, Akram AR, Hill AT (2010) Statins in community acquired pneumonia: evidence from experimental and clinical studies. Respir Med 104(8):1081–1091

    PubMed  Article  Google Scholar 

  2. Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4:977–987

    PubMed  Article  CAS  Google Scholar 

  3. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R (2005) Efficacy and safety of cholesterol lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366:1267–1278

    PubMed  Article  CAS  Google Scholar 

  4. Fedson DS (2006) Pandemic influenza: a potential role for statins in treatment and prophylaxis. Clin Infect Dis 43:199–205

    PubMed  Article  CAS  Google Scholar 

  5. Alegret M, Silvestre JS (2006) Pleiotropic effects of statins and related pharmacological experimental approaches. Methods Find Exp Clin Pharmacol 28:627–656

    PubMed  Article  CAS  Google Scholar 

  6. Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egido J (2003) Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 63:12–23

    PubMed  Article  CAS  Google Scholar 

  7. Novack V, Terblanche M, Almog Y (2006) Do statins have a role in preventing or treating sepsis? Crit Care 10:113

    PubMed  Article  Google Scholar 

  8. Schonbeck U, Libby P (2004) Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as anti-inflammatory agents? Circulation 109[21 suppl 1]:II18–II26

    PubMed  Google Scholar 

  9. Almog Y (2003) Statins, inflammation, and sepsis: hypothesis. Chest 124:740–743

    PubMed  Article  CAS  Google Scholar 

  10. Almog Y, Novack V, Eisinger M, Porath A, Novack L, Gilutz H (2007) The effect of statin therapy on infection related mortality in patients with atherosclerotic diseases. Crit Care Med 35:372–378

    PubMed  Article  CAS  Google Scholar 

  11. 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 110:880–885

    PubMed  Article  CAS  Google Scholar 

  12. Liappis AP, Kan VL, Rochester CG, Simon GL (2001) The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 33:1352–1357

    PubMed  Article  CAS  Google Scholar 

  13. Schlienger RG, Fedson DS, Jick SS, Jick H, Meier CR (2007) Statins and the risk of pneumonia: a population-based, nested case-control study. Pharmacotherapy 27(3):325–332

    PubMed  Article  CAS  Google Scholar 

  14. van den Garde EMW, Hak E, Souvereins PC, Hoes AW, van den Bosch JMM, Leufkens HGM (2006) Statin treatment and reduced risk of pneumonia in patients with diabetes. Thorax 61:957–961

    PubMed  Article  Google Scholar 

  15. Dublin S, Jackson ML, Nelson JC, Weiss NS, Larson EB, Jackson LA (2009) Statin use and risk of community acquired pneumonia in older people: population based case-control study. Br Med J 338:b2137. doi:10.1136/bmj.b2137

    Article  Google Scholar 

  16. Fleming DM, Verlander NQ, Elliot AJ, Zhao H, Gelb D, Jehring D, Nguyen-van-tam JS (2010) An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 1998–1999 to 2005–2006. Epidemiol Infect 138:1281–1288

    PubMed  Article  CAS  Google Scholar 

  17. Kwong JC, Li P, Redelmeier DA (2009) Influenza morbidity and mortality in elderly patients receiving statins: a cohort study. PLoS ONE 4(11):8087

    Article  Google Scholar 

  18. Douglas I, Evans S, Smeeth L (2011) Effect of statin treatment on short term mortality after pneumonia episode: cohort study. Br Med J 342:d1642

    Article  Google Scholar 

  19. Yende S, Milbrandt EB, Kellum JA, Kong L, Delude RL, Weissfeld LA, Angus DC (2011) Understanding the role of statins in pneumonia and sepsis. Crit Care Med 39(8):1871–1878

    Google Scholar 

  20. Singh S, Loke YK, Furberg CD (2011) Long-term use of thiazolidinediones and the associated risk of pneumonia or lower respiratory tract infection: systematic review and meta-analysis. Thorax 66(5):383–388

    PubMed  Article  Google Scholar 

  21. Loke YK, Price D, Herxheimer A (2008) Chapter 14: adverse effects. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions. John Wiley & Sons, Chichester

    Google Scholar 

  22. Ioannidis JP, Trikalinos TA (2007) The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. Can Med Assoc J 176(8):1091–1096

    Google Scholar 

  23. Davies HT, Crombie IK, Tavakoli M (1998) When can odds ratios mislead? Br Med J 316(7136):989–991

    Article  CAS  Google Scholar 

  24. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327(7414):557–560

    Article  Google Scholar 

  25. Le Manach Y, Ibanez Esteves C, Bertrand M, Goarin JP, Fleron MH, Coriat P, Koskas F, Fiou B, Landais P (2011) Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing vascular surgery. Anesthesiology 114(1):98–104

    PubMed  Article  Google Scholar 

  26. Myles PR, Hubbard RB, McKeever TM, Pogson Z, Smith CJ, Gibson JE (2009) Risk of community-acquired pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study. Pharmacoepidemiol Drug Saf 18(4):269–275

    PubMed  Article  CAS  Google Scholar 

  27. Rodriguez de Antonio LA, Martinez-Sanchez P, Martinez-Martinez MM, Cazorla-Garcia R, Sanz-Gallego FB, Diez-Tejedor E (2011) Previous statins treatment and risk of post-stroke infections. Neurologia 26:150–156

    PubMed  Article  CAS  Google Scholar 

  28. Smeeth L, Douglas I, Hall AJ, Hubbard R, Evans S (2009) Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol 67(1):99–109

    PubMed  Article  Google Scholar 

  29. Ioannidis JP, Patsopoulos NA, Rothstein HR (2008) Reasons or excuses for avoiding meta-analysis in forest plots. Br Med J 336:1413–1415

    Article  Google Scholar 

  30. Majumdar SR, McAlister FA, Eurich DT, Padwal RS, Marrie TJ (2006) Statins and outcomes in patients admitted to hospital with community acquired pneumonia: population based prospective cohort study. Br Med J 333(7576):999

    Article  Google Scholar 

  31. Schisterman EF, Cole SR, Platt RW (2009) Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology 20(4):488–495

    PubMed  Article  Google Scholar 

  32. Fessler MB, Young SK, Jeyaseelan S, Lieber JG, Arndt PG, Nick JA, Worthern GS (2005) A role for hydroxy-methylglutaryl coenzyme a reductase in pulmonary inflammation and host defense. Am J Respir Crit Med 171(6):606–615

    Article  Google Scholar 

  33. Whittle J, Fine MJ, Joyce DZ, Lave JR, Young WW, Hough LJ, Kapoor WN (1997) Community-acquired pneumonia: can it be defined with claims data? Am J Med Qual 12(4):187–193

    PubMed  Article  CAS  Google Scholar 

  34. Beri A, Surai N, Mahajan SB (2009) Non-atheroprotective effects of statins: a systematic review. Am J Cardiovasc Drugs 9(6):361–370

    PubMed  Article  CAS  Google Scholar 

  35. Hippisley-Cox J, Coupland C (2010) Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. Br Med J 340:c2197. doi:10.1136/bmj.c2197

  36. Marston BJ, Plouffe JF, File TM Jr, Hackman BA, Salstrom SJ, Lipman HB, Kolczak MS, Breiman RF (1997) Incidence of community-acquired pneumonia requiring hospitalization Results of a population-based active surveillance study in Ohio. The Community-Based Pneumonia Incidence Study Group. Arch Intern Med 157(15):1709–1718

    PubMed  Article  CAS  Google Scholar 

  37. Loke YK, Kwok CS, Niruban A, Myint PK (2010) Value of severity scales in predicting mortality from community-acquired pneumonia: systematic review and meta-analysis. Thorax 65(10):884–890

    PubMed  Article  Google Scholar 

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Acknowledgments

There was no funding source for this study. The authors have no conflicts of interest to declare.

Contributors

CSK, YKL and SS conceptualised the review and developed the protocol. CSK, JKY, RT, YKL, RC and SS abstracted data. CSK and YKL wrote the manuscript. Data was analysed by CSK and YKL. YKL will act as the guarantor for the paper.

Funding

None

Author information

Affiliations

  1. School of Medicine, University of East Anglia, Norwich, NR4 7TJ, UK

    Chun Shing Kwok, Jessica Ka-Yan Yeong & Yoon Kong Loke

  2. Norfolk and Norwich University Hospital, Colney Lane, Norwich, NR4 7UY, UK

    Richard M. Turner

  3. Department of Medicine, University of Louisville, Louisville, KY, 40202, USA

    Rodrigo Cavallazzi

  4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Sonal Singh

Authors
  1. Chun Shing Kwok
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  2. Jessica Ka-Yan Yeong
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  3. Richard M. Turner
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  4. Rodrigo Cavallazzi
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  5. Sonal Singh
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  6. Yoon Kong Loke
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Correspondence to Yoon Kong Loke.

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Kwok, C.S., Yeong, J.KY., Turner, R.M. et al. Statins and associated risk of pneumonia: a systematic review and meta-analysis of observational studies. Eur J Clin Pharmacol 68, 747–755 (2012). https://doi.org/10.1007/s00228-011-1159-4

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  • DOI: https://doi.org/10.1007/s00228-011-1159-4

Keywords

  • Statins
  • Pneumonia
  • Meta-analysis