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Epidemiological evidence for a protective role for statins in Community Acquired Pneumonia

Epidemiological evidence for a protective role for statins in Community Acquired Pneumonia. Yana Vinogradova . British Thoracic Society Winter Meeting 2012 , London. Background. Statins – common medications, 24% in 45+ age group.

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Epidemiological evidence for a protective role for statins in Community Acquired Pneumonia

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  1. Epidemiological evidence for a protective role for statins in Community Acquired Pneumonia Yana Vinogradova British Thoracic Society Winter Meeting 2012 , London

  2. Background Statins – common medications, 24% in 45+ age group. CAP – common infection, 230 per 100,000 person-years, 670 for 60+ age group. Evidence from lab data that statins may benefit in cases of infectious diseases

  3. From: Does Statin Use Improve Pneumonia Outcomes? Chopra, Flanders, CHEST. 2009;136(5):1381-1388. doi:10.1378/chest.09-0941 Figure Legend: Pleiotropic effects of statins. eNOS = endothelial nitric oxide synthase; PAI-1 = plasminogen activator inhibitor-1; NADPH = nicotinamide adenine dinucleotide phosphate hydrogen; MCP1 = monocyticchemoattractant protein 1; TNF = tumor necrosis factor; LFA-1 = lymphocyte function-associated antigen-1.

  4. Pharmacoepidemiology and Prescription From: Statins and associated risk of pneumonia: a systematic review and meta-analysis of observational studies Kwok et al. Eur J ClinPharmacol (2012) 68, 747-755 Fig. 3 Meta-analysis of adjusted risk of pneumonia with statin therapy

  5. QResearch • 660 GP practices • Currently largest database in the UK • 537 UK practices • > 6 practices in every SHA • > 9 million patients including those who died, left and still registered • > 30 million person years of observation Patient level data from GP clinical records Anonymised Longitudinal data for 20+ years Validated externally and internally Industry independent

  6. Methods: Study design and analysis Nested case control study Study period Jan 1996-Dec 2005 Cases were incident CAP patients 5 controls matched by age, sex, practice analysis restricted to subjects with at least 2 years of prescribing data Conditional logistic regression, odds ratios 95%CI

  7. Methods: Assessment of Exposure use: at least 2 scripts in 12 months prior to the index date different types of statins atorvastatin pravastatin cerivastatin simvastatin fluvastatin rosuvastatin time before the index date: 28 days 29-89 days 90-365 days

  8. Methods: Confounding factors • Morbidities • List of co-morbidities recommended for pneumococcal vaccination • Additional co-morbidities limiting mobility or suppressing immune system • Medications • Acid-lowering drugs • Socio-economic status • Townsend quintiles • Smoking status • Non-smoker • Smoker • not recorded • Vaccinations • Influenza • pneumococcal

  9. Results: Sample and statin use in the last year

  10. Crude OR, 95%CI 1.23, 1.13 – 1.33 Crude OR, 95%CI 1.25, 1.16 – 1.34

  11. 9% 7% 11% 13% 37% 30% 55% 62% Crude OR, 95%CI 1.27, 1.20 – 1.34 1.14, 1.08 – 1.20 1.03, 0.98 – 1.09

  12. 70% 69% 63% 60% 38% 48%

  13. 23% 37% 26% 31% CHD and stroke Crude OR, 95%CI 2.18, 2.10 – 2.27 Statin use, OR, 95%CI Crude 1.24, 1.18 – 1.31 Adjusted 0.81, 0.77 – 0.86

  14. Limitations • Residual confounding as no information • on X-ray • on microbiological tests • on severity of pneumonia • Information on prescriptions only • Over-the-counter statin use • Missing data Strengths • Large sample size and representative population • Data electronically collected – unlikely misclassification bias • Data collected before diagnosis – no recall bias • All cases used – no selection bias

  15. Further research • RCT in 26 countries • Randomisation in 2003-2006, last visit in 2008 • 17802 participants with no history of CVD and diabetes • Rosuvastatin 20mg or placebo • Incidence of infections during the trial

  16. HR (95%CI) 1st CAP 0.81 (0.67 – 1.97) Figure 2: Kaplan–Meier estimates from intention-to-treat analysis showing cumulative incidence of first pneumonia adjusted for competing risk of cardiovascular events. Participants were censored at the time of a cardiovascular event.

  17. Further research Danish National Registry 1997-2009, additional analysis for 2001-2009 70,914 patients hospitalised with pneumonia Matched to up to 10 controls Current statin use: at least 1 prescription in last 125 days Adjusted for co-morbidities, medications, smoking, demographics...

  18. Conclusions There is an association between use of statins and decreased risk of pneumonia, more pronounced for patients having recent statin use. It may be due to anti-inflammatory and immunomodulatory properties of statins It may also be due to reduced rate of CVD events and rates of associated complication such as pneumonia

  19. Thank you Questions?

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