Do statins affect risk of pneumonia in the general population: nested case control study Yana Vinogradova Julia Hippisley-Cox Calgary2007

Aims of presentation Research study –Present analysis of study determining the risk of community acquired pneumonia in patients taking statins

Background to pneumonia statin analysis Some evidence from lab data that statins benefit in case of infectious diseasesSome evidence from lab data that statins benefit in case of infectious diseases Statins can reduce rate of severe sepsis and ICU admissionStatins can reduce rate of severe sepsis and ICU admission Significant reduction in mortalitySignificant reduction in mortality Reduction in fatal pneumonia riskReduction in fatal pneumonia risk 51% reduction in diabetes patients51% reduction in diabetes patients

Study population: QRESEARCH database Currently largest database in the UKCurrently largest database in the UK 537 UK practices537 UK practices > 6 practices in every Strategic Health Authority (administrative area)> 6 practices in every Strategic Health Authority (administrative area) > 9 million patients including those who died, left and still registered> 9 million patients including those who died, left and still registered > 30 million person years of observation> 30 million person years of observation

Data source: QRESEARCH database Patient level consolidated databasePatient level consolidated database Anonymised dataAnonymised data Longitudinal data for 15+ yearsLongitudinal data for 15+ years Derived from GP clinical recordsDerived from GP clinical records Validated against external and internal measuresValidated against external and internal measures Industry independentIndustry independent

Study design & setting Nested case control studyNested case control study Study period Jan 1996-Dec 2005Study period Jan 1996-Dec 2005 Cases were incident community- acquired pneumonia patientsCases were incident community- acquired pneumonia patients 5 controls matched by5 controls matched by –Age –Sex –Practice –Calendar year

Assessment of exposure analysis restricted to subjects with at least 2 years of prescribing data use:use: at least 2 script in 12 months prior to the index date different types of statinsdifferent types of statins atorvastatinpravastatincerivastatin simvastatinfluvastatinrosuvastatin time for the last prescription:time for the last prescription: 28 days days days

Statistical analysis Conditional logistic regressionConditional logistic regression Odds ratios + 95% CIOdds ratios + 95% CI Unadjusted & adjustedUnadjusted & adjusted

Confounding factors Socio-economic status Townsend quintiles Body mass index Less than 25 kg/m2 25 to 29.9 kg/m2 30 kg/m2 or more BMI not recorded Smoking status Non-smoker Smoker not recorded Morbidities List of comorbidites recommended for pneumococcal vaccination Additional comorbidities limiting mobility or suppressing immune systemVaccinations Influenza pneumococcal

Risk group for pneumococcal vaccine from current CMO guidance DiabetesDiabetes Chronic heart diseaseChronic heart disease Chronic renal diseaseChronic renal disease Chronic respiratory diseaseChronic respiratory disease AspleniaAsplenia CSF ShuntCSF Shunt Chronic liver diseaseChronic liver disease Sickle cell or Coeliac diseaseSickle cell or Coeliac disease Cochlear ImplantCochlear Implant HIV/AIDSHIV/AIDS ImmunosuppressedImmunosuppressed

New potential risk group New conditions selected becauseNew conditions selected because –they limit the mobility –or can be associated with immunosuppression Diseases includedDiseases included –Stroke or TIA –Rheumatoid arthritis –Parkinson’s disease –Common cancers –Multiple sclerosis –Dementia –Osteoporosis

Sample 34,098 incident cases of CAP 1995/ ,718 cases older than 44 years 17,757 cases with 2 years of medical records

Use of statin in the last 12 months Cases CasesN=17,757 Controls ControlsN=80,487 Unadjusted Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI) 2,244 2,244 (12.6%) (12.6%) 8,788 8,788 (10.9%) (10.9%) (1.18 – 1.31) (1.18 – 1.31) (0.77 – 0.87) (0.77 – 0.87) Adjusted for socio-economic status, body-mass index, smoking status, use of influenza and pneumococcal vaccinations and the co-morbidities

Main findings any use of statin: 13% to 23% decrease of pneumonia risk13% to 23% decrease of pneumonia risk use of statin within the last 28 days: 22% to 32% decrease of risk22% to 32% decrease of risk

Methodological strengths Large sample size and representative populationLarge sample size and representative population Data electronically collected – unlikely misclassification biasData electronically collected – unlikely misclassification bias Data collected before the diagnosis – no recall biasData collected before the diagnosis – no recall bias

Methodological weaknesses Misclassification bias: no x-ray or microbiological confirmationMisclassification bias: no x-ray or microbiological confirmation Misclassification of use: over-the- counter purchaseMisclassification of use: over-the- counter purchase Data contain information on prescription, not actual useData contain information on prescription, not actual use Information on certain risk factors (alcohol intake)Information on certain risk factors (alcohol intake) Missing data for BMI, smokingMissing data for BMI, smoking

Conclusions Recent use of statin is associated with reduced risk of community acquired pneumoniaRecent use of statin is associated with reduced risk of community acquired pneumonia

Acknowledgements QRESEARCH team –UoN –EMIS

Read code Term H2Pneumonia and influenza H21Lobar (pneumococcal) pneumonia H21-1Chest infection – pneumococcal pneumonia H22Other bacterial pneumonia H22-1Chest infection – other bacterial pneumonia H223Pneumonia due to streptococcus H22yzPneumonia due to bacteria NOS H22zBacterial pneumonia NOS H23-1Chest infection – pneumonia organism OS H25Bronchopneumonia due to unspecified organism H25-1Chest infection – unspecified bronchopneumonia H26Pneumonia due to unspecified organism H260Lobar pneumonia due to unspecified organism H261Basal pneumonia due to unspecified organism H262Postoperative pneumonia H270Influenza with pneumonia H270-1Chest infection – influenza with pneumonia H2700Influenza with bronchopneumonia H2701Influenza with pneumonia, influenza virus identified H270zInfluenza with pneumonia NOS H28Atypical pneumonia H2yOther specified pneumonia or influenza H2zPneumonia or influenza NOS