1. The effect of the ‘Polypill’ on mortality in general practice Dr Julia Hippisley-Cox Gozo October 2004

2. Goals of presentation To given an over view of electronic database used for the study (QRESEARCH)To given an over view of electronic database used for the study (QRESEARCH) To describe research to determine effect of the ‘Polypill’ on mortality in patients with CHDTo describe research to determine effect of the ‘Polypill’ on mortality in patients with CHD

3. GP databases in the UK Several different database availableSeveral different database available –Oldest and most well known GPRD QRESEARCH new key databasesQRESEARCH new key databases Both derived from GP clinical dataBoth derived from GP clinical data Both available for access by researchersBoth available for access by researchers Both are an international resourceBoth are an international resource

4. QRESEARCH What is it? QR is result of a not-for-profit partnership between UoN & EMIS [supplies > 60% all practices]QR is result of a not-for-profit partnership between UoN & EMIS [supplies > 60% all practices] Patient level consolidated databasePatient level consolidated database Longitudinal data for up to 16 yearsLongitudinal data for up to 16 years Validated against external and internal measuresValidated against external and internal measures

5. Qresearch Coverage 468+ practices468+ practices UK wideUK wide > 5 in every SHA> 5 in every SHA Approx 7.4 million patients including those who died, left and still registeredApprox 7.4 million patients including those who died, left and still registered 3.3 million current patients3.3 million current patients Now the largest such database in the world (unless anyone here knows otherwise!)Now the largest such database in the world (unless anyone here knows otherwise!)

6. Data contents Socio-demographicsSocio-demographics DiagnosesDiagnoses Clinical valuesClinical values Laboratory testsLaboratory tests Prescription dataPrescription data Consultation dataConsultation data Category of clinician entering dataCategory of clinician entering data

7. QRESEARCH Research service We will provide a service to -Bona fide academics -With original research question -With MREC -With freedom to publish -Who agree to -Acknowledge source data -use it for purpose only -not pass it on

8. What type of research can we use it for? Best for epidemiological studies Case control studiesCase control studies Cohort studiesCohort studies Cross sectional surveyCross sectional survey ModellingModelling

9. Things we cant do: Track back to patientsTrack back to patients Track back to practicesTrack back to practices Randomise patients or practicesRandomise patients or practices Link with external data sources eg questionnaire, geneticsLink with external data sources eg questionnaire, genetics This is where other systems come inThis is where other systems come in -THIN -e-GRID –UK Biobank

10. Aims of research project To determine the effect of the ‘Polypill’ on mortality in CHD patientsTo determine the effect of the ‘Polypill’ on mortality in CHD patients Polypill = aspirin + beta blockers + ACE inhibitors + statinsPolypill = aspirin + beta blockers + ACE inhibitors + statins

11. Background to project Good evidence from individual trials for benefits of individual drugs in 2’ prevention CHDGood evidence from individual trials for benefits of individual drugs in 2’ prevention CHD Enthusiasm for ‘Polypill’ for all patients over 55 years though no direct evidence benefits stack upEnthusiasm for ‘Polypill’ for all patients over 55 years though no direct evidence benefits stack up Drugs may interact with drugs or other comorbidityDrugs may interact with drugs or other comorbidity

12. Design & setting Design Open cohort study with case control analysisOpen cohort study with case control analysisSetting 1.18 million patients registered with 89 QRESEARCH practices on 1 st Jan 19961.18 million patients registered with 89 QRESEARCH practices on 1 st Jan 1996 All practices had a minimum of 8 years of complete computerised dataAll practices had a minimum of 8 years of complete computerised data

13. Study cohort All patients with a 1 st diagnosis of CHD between 1 st Jan 96 and 31 Dec 2003All patients with a 1 st diagnosis of CHD between 1 st Jan 96 and 31 Dec 2003 Study period chosen as statins only in common use after Jan 96Study period chosen as statins only in common use after Jan 96

14. Cases & controls Cases were CHD patients who died during study periodCases were CHD patients who died during study period Controls were CHD patients who didn’t die matched forControls were CHD patients who didn’t die matched for –Age –Year of birth –Sex Four controls per caseFour controls per case

15. Index date Assigned index date to each case [date of death]Assigned index date to each case [date of death] Assigned same date to matched controlsAssigned same date to matched controls Reviewed medical & drug history prior to this dateReviewed medical & drug history prior to this date

16. Outcomes Odds ratio (95% CI) for all cause mortality in cases vs controlsOdds ratio (95% CI) for all cause mortality in cases vs controls ExposureExposure –combinations of aspirin, statins, beta blockers and ACE inhibitors Adjusted forAdjusted for –Comorbidity (MI, Diabetes, hypertension, CCF) –Smoking –obesity –deprivation

17. Statistics Conditional logistic regression using STATA v8.2Conditional logistic regression using STATA v8.2 Examined for 2 way interactionsExamined for 2 way interactions – drug*drug – drug*disease Included significant interactions in modelIncluded significant interactions in model Selected p < 0.01Selected p < 0.01

18. PRELIMINARY RESTULS study population 1.17 million patients in population 13,029 patients with CHD 2,266 deaths So 2,266 cases + 9064 matched controls

19. Comparison with 4S study Patients on statins had 37% lower risk of death c.f. those not on statinsPatients on statins had 37% lower risk of death c.f. those not on statins This is similar to the 30% reduction in risk reported in 4S studyThis is similar to the 30% reduction in risk reported in 4S study Marginally greater benefit as our population higher risk than trial populationMarginally greater benefit as our population higher risk than trial population

20. Odds ratio for death Combination Adjusted odds ratio* Statin + aspirin + BB + ACE 0.63 (95% 0.51-0.79) Statins + aspirin + BB 0.43 (95% 0.34-0.55) * Adjusted for CCF, diabetes, hypertension, MI, smoking, obesity, deprivation etc

21. In other words Despite adjustment for comorbidity, patients on combination of :Despite adjustment for comorbidity, patients on combination of : –3 drugs had 57% lower risk of death –4 drugs had 37 % lower risk of death Combination without ACE was betterCombination without ACE was better

22. Discussion of methodology Case control study but Very large sampleVery large sample No recall biasNo recall bias No selection biasNo selection bias Misclassification unlikely as drugs all prescribed except aspirin which is also OTCMisclassification unlikely as drugs all prescribed except aspirin which is also OTC

23. Possible explanations We found significant statistical interaction between ACEI and statinsWe found significant statistical interaction between ACEI and statins Possible explanationsPossible explanations –? misclassification of CCF (but no interaction between other drugs) –? Chance finding Whatever, study challenges assumptions that benefits automatically stack up in ‘real life populations’Whatever, study challenges assumptions that benefits automatically stack up in ‘real life populations’

24. Next Steps Thank you for listening Ideas and questions welcome!