The effect of the ‘Polypill’ on mortality in general practice

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 describe research to determine effect of the ‘Polypill’ on mortality in patients with CHD

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

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

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

6. Data contents • Socio-demographics • Diagnoses • Clinical values • Laboratory tests • Prescription data • Consultation data • Category 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 studies • Cohort studies • Cross sectional survey • Modelling

9. Things we cant do: • Track back to patients • Track back to practices • Randomise patients or practices • Link with external data sources eg questionnaire, genetics • This 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 patients • Polypill = aspirin + beta blockers + ACE inhibitors + statins

11. Background to project • Good 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 up • Drugs may interact with drugs or other comorbidity

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

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

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

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

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

17. Statistics • Conditional logistic regression using STATA v8.2 • Examined for 2 way interactions • drug*drug • drug*disease • Included significant interactions in model • Selected 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 statins • This is similar to the 30% reduction in risk reported in 4S study • Marginally greater benefit as our population higher risk than trial population

20. Odds ratio for death * Adjusted for CCF, diabetes, hypertension, MI, smoking, obesity, deprivation etc

21. In other words • 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 better

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

23. Possible explanations • We found significant statistical interaction between ACEI and statins • Possible 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’

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