do statins affect risk of pneumonia in the general population: nested case control study yana...
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Do statins affect risk of Do statins affect risk of pneumonia in the general pneumonia in the general
population: nested case control population: nested case control studystudy
Yana VinogradovaYana VinogradovaJulia Hippisley-Cox Julia Hippisley-Cox
CalgaryCalgary20072007
Aims of presentationAims of presentation
Research study Research study – Present analysis of study determining the
risk of community acquired pneumonia in patients taking statins
Background to pneumonia Background to pneumonia statin analysis statin analysis
• Some evidence from lab data that Some evidence from lab data that statins benefit in case of infectious statins benefit in case of infectious diseasesdiseases
• Statins can reduce rate of severe Statins can reduce rate of severe sepsis and ICU admissionsepsis 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: Study population: QRESEARCH databaseQRESEARCH database
• Currently largest database in the UKCurrently largest database in the UK• 537 UK practices537 UK practices• > 6 practices in every Strategic Health > 6 practices in every Strategic Health
Authority (administrative area)Authority (administrative area)• > 9 million patients including those who > 9 million patients including those who
died, left and still registereddied, left and still registered• > 30 million person years of observation> 30 million person years of observation
Data source: Data source: QRESEARCH databaseQRESEARCH 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 Validated against external and internal measuresmeasures
• Industry independent Industry independent
Study design & settingStudy design & setting
• Nested case control studyNested case control study• Study period Jan 1996-Dec 2005 Study period Jan 1996-Dec 2005 • Cases were incident community-Cases were incident community-
acquired pneumonia patientsacquired pneumonia patients• 5 controls matched by 5 controls matched by
– Age– Sex– Practice– Calendar year
Assessment of exposureAssessment of exposureanalysis restricted to subjects with at least 2 years of analysis restricted to subjects with at least 2 years of
prescribing dataprescribing data
• useuse:: at least 2 script in 12 months prior to the index date
• different types of statinsdifferent types of statinsatorvastatin pravastatin cerivastatinsimvastatin fluvastatin rosuvastatin
• time for the last prescriptiontime for the last prescription: : 28 days29-89 days90-365 days
Statistical analysisStatistical analysis
• Conditional logistic regressionConditional logistic regression
• Odds ratios + 95% CIOdds ratios + 95% CI
• Unadjusted & adjustedUnadjusted & adjusted
Confounding factorsConfounding factorsSocio-economic Socio-economic statusstatus
• Townsend quintiles
Body mass indexBody mass index• Less than 25 kg/m2• 25 to 29.9 kg/m2• 30 kg/m2 or more• BMI not recorded
Smoking statusSmoking status• Non-smoker• Smoker• not recorded
MorbiditiesMorbidities• List of comorbidites
recommended for pneumococcal vaccination
• Additional comorbidities limiting mobility or suppressing immune system
VaccinationsVaccinations• Influenza• pneumococcal
Risk group for pneumococcal vaccine Risk group for pneumococcal vaccine from current CMO guidancefrom 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 groupNew potential risk group• New conditions selected because New 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
SampleSample
34,098 incident cases of CAP 1995/2006
22,718 cases older than 44 years
17,757 cases with 2 years of medical records
11.0
7.6
29.7
17.8
1.80.7
30.4
14.1
0.8 0.3 0.3 0.2 0.1 0.0
15.1
10.4
0
5
10
15
20
25
30
Pro
por
tion
of p
atie
nts
(%
)
Diabetes Heart Renal Chest Liver SC/CD HIV Immunosup© QRESEARCH 2006 version 11
Proportions of patients with current risk group diseases
cases controls
13.5
7.6
3.3
1.6 2.21.1 0.7 0.2
4.1
1.6
5.2
3.1
9.7
6.0
0
5
10
15
20
25
30
Pro
por
tion
of p
atie
nts
(%
)
Stroke RA Parkinson MS Dementia OP Any cancer© QRESEARCH 2006 version 11
Proportions of patients with additional risk group diseases
cases controls
Immunosuppressed
Sickle cell/ Coeliac disiase
Liver disease
Respiratory disease
Renal disease
Heart disease
Diabetes
1 1.5 2 2.5 3Adjusted for deprivation, smoking, years of data, use of flu and pneumo vaccines, all diseases and statins© QRESEARCH 2006 version 11
all patientsAdjusted odds ratios and 95% confidence intervals for current risk group
Any cancer
Osteoporosis
Dementia
Multiple sclerosis
Parkinson's disease
Rheumatoid arthritis
Stroke/TIA
1 1.5 2 2.5 3 3.5 4 4.5 5Adjusted for deprivation, smoking, years of data, use of flu and pneumo vaccines, all diseases and statins© QRESEARCH 2006 version 11
all patientsAdjusted odds ratios and 95% confidence intervals for additional risk group
Use of statin in the last 12 monthsUse of statin in the last 12 months
Cases Cases
N=17,757N=17,757
ControlsControls
N=80,487N=80,487
Unadjusted Unadjusted Odds RatioOdds Ratio
(95% CI)(95% CI)
Adjusted Adjusted Odds Ratio Odds Ratio
(95% CI)(95% CI) 2,244 2,244
(12.6%)(12.6%)
8,7888,788
(10.9%)(10.9%)
1.241.24
(1.18 – 1.31)(1.18 – 1.31)
0.820.82
(0.77 – 0.87)(0.77 – 0.87)
Adjusted for socio-economic status, body-mass index, Adjusted for socio-economic status, body-mass index, smoking status, use of influenza and pneumococcal smoking status, use of influenza and pneumococcal vaccinations and the co-morbidities vaccinations and the co-morbidities
4.44.0
0.1 0.10.4 0.4
1.1 0.9
6.6
5.5
0.1 0.00
1
2
3
4
5
6
7
8
9
Pro
por
tion
of p
atie
nts
(%
)
Atorvastatin Cerivastatin Fluvastatin Pravastatin Simavastatin Rosuvastatin© QRESEARCH 2006 version 11
Proportions of patients taking different statins
cases controls
1
.25
.5
.75
1
1.25
1.5
1.75
2
Atorvastatin Cerivastatin Fluvastatin Pravastatin Simavastatin Rosuvastatin
Odds ratio lower/upper limits of 95%CI
Adj
uste
d O
dds
Rat
io
4.4/ 4.0% 0.1/ 0.1% 0.4/ 0.4% 1.1/ 0.9% 6.6/ 5.5% 0.1/ 0.0%
785/ 3187 25/ 93 63/ 291 188/ 743 1174/ 4438 9/ 36
copyright QRESEARCH 2007
N of cases/ N of controls:
Adjusted odds ratios for use of different statins
7.47.1
4.1
3.0
1.10.8
0
1
2
3
4
5
6
7
8
9
10
Pro
port
ion
of p
atie
nts
(%)
1-28d 29-89d 90-365d
Proportions of statin users
cases
controls
1
.5
.6
.7
.8
.9
1
1.1
1.2
Ad
just
ed
Odd
s R
atio
1-28d 29-89d 90-365d
Adjusted odds ratios and 95% CI
Odds ratios adjusted for deprivation, smoking,use of flu and pneumococcal vaccines, risk groups© QRESEARCH 2006 version 11
Last prescription of statin
Main findingsMain findings
any use of statin: any use of statin:
• 13% to 23% decrease of pneumonia 13% to 23% decrease of pneumonia riskrisk
use of statin within the last 28 days: use of statin within the last 28 days:
• 22% to 32% decrease of risk22% to 32% decrease of risk
Methodological strengthsMethodological strengths
• Large sample size and representative Large sample size and representative populationpopulation
• Data electronically collected – Data electronically collected – unlikely misclassification bias unlikely misclassification bias
• Data collected before the diagnosis – Data collected before the diagnosis – no recall biasno recall bias
Methodological weaknessesMethodological weaknesses
• Misclassification bias: no x-ray or Misclassification bias: no x-ray or microbiological confirmationmicrobiological confirmation
• Misclassification of use: over-the-Misclassification of use: over-the-counter purchasecounter purchase
• Data contain information on Data contain information on prescription, not actual useprescription, not actual use
• Information on certain risk factors Information on certain risk factors (alcohol intake) (alcohol intake)
• Missing data for BMI, smokingMissing data for BMI, smoking
ConclusionsConclusions
• Recent use of statin is associated with Recent use of statin is associated with reduced risk of community acquired reduced risk of community acquired pneumoniapneumonia
Read codeTerm
H2 Pneumonia and influenza
H21 Lobar (pneumococcal) pneumonia
H21-1 Chest infection – pneumococcal pneumonia
H22 Other bacterial pneumonia
H22-1 Chest infection – other bacterial pneumonia
H223 Pneumonia due to streptococcus
H22yz Pneumonia due to bacteria NOS
H22z Bacterial pneumonia NOS
H23-1 Chest infection – pneumonia organism OS
H25 Bronchopneumonia due to unspecified organism
H25-1 Chest infection – unspecified bronchopneumonia
H26 Pneumonia due to unspecified organism
H260 Lobar pneumonia due to unspecified organism
H261 Basal pneumonia due to unspecified organism
H262 Postoperative pneumonia
H270 Influenza with pneumonia
H270-1 Chest infection – influenza with pneumonia
H2700 Influenza with bronchopneumonia
H2701 Influenza with pneumonia, influenza virus identified
H270z Influenza with pneumonia NOS
H28 Atypical pneumonia
H2y Other specified pneumonia or influenza
H2z Pneumonia or influenza NOS