BSG Annual Meeting, Birmingham 15 th March 2011

1. Is low-dose Aspirin use associated with a reduced risk of colorectal cancer ? a QResearch primary care database analysis Prof Richard Logan, Dr Yana Vinogradova, Dr Carol Coupland, Prof Julia Hippisley-Cox, Divisions of Primary Care, and Epidemiology & Public Health, University of Nottingham, UK BSG Annual Meeting, Birmingham 15th March 2011

2. Cohort studies of Colorectal Cancer in NSAID users

3. Low-Dose Aspirin in the Primary Prevention of Cancer (Cook et al. JAMA 2005) Aspirin 50mg/day Placebo Rel Risk Colon 103 / 111 0.92 Rectum 30 / 25 1.20 Colorectal 133 / 136 0.97 (0.77-1.24) Average of 10 years of treatment

4. Incidence of colorectal cancer in aspirin trials (from Cuzick et al Lancet Oncol 2009)

5. Vinogradova et al. Gastroenterology 2007

6. Vinogradova et al. Gastroenterology 2007

7. Lancet Oct 22 2010 (n=391) 5yr 10yr 15yr 20yr 5yr 10yr 15yr 20yr

8. Lancet Dec 7 2010 Risk of death from CRC 5yr 20yr 10yr 15yr

9. Study population: QRESEARCH database • Currently largest primary care database in the UK • 574 general practices across the UK • > 9 million patients including those who have died or left, as well as patients still registered • > 30 million person-years of observation

10. Data source: QRESEARCH database • Derived from GP clinical records • Patient level consolidated database • Anonymised data • Longitudinal data for 15+ years • Validated against external and internal measures

11. Study design & setting • Nested case control study • Study period Jan 1998-July 2008 • Cases were incident colorectal cancer patients • 5 controls matched by • Age • Sex • Practice • Calendar year

12. Exposureassessment : • Aspirin exposure analysis restricted to subjects with +10 and +15yrs of prescribing data • any use: • at least 1 script in 13-120 months and 13 to 180 months prior to the index date (date of diagnosis in the case) • Years of exposure: • up to 1 years • 1 to 2 years • 3 to 5 years • 6 to 9 years • 10 to 14 years

13. Statistical analysis • Multiple imputations • ICE procedure in STATA • 5 imputed datasets • Rubin’s rule’s to combine estimates • Conditional logistic regression • Odds ratios + 95% CI ( unadjusted & adjusted) • 1% significance level

14. Study Sample:

15. Body mass index in kg/m2 Smoking status Non-smoker Ex-smoker Smoker Socio-economic status (Townsend score for post code) quintiles Morbidities CVD Diabetes High BP Osteoarthritis Colitis Crohn’s disease Rheumatoid arthritis Confounding factors :

16. Aspirin – median dose prescribed 10 year cohort 15 year cohort Tablet dose (n = 10,073) (n = 6,506) ≥ 75 mg 77% 78% 76 – 150 mg 16% 15% 151 – 300 mg 5% 5% >300 mg 2% 2%

17. Aspirin – frequency of use recommended Daily 65% Twice daily 15% Alternate days 5%

18. Cumulative exposure to aspirin in 1 to 15 yr period prior to CRC diagnosis / index date

19. Risk of Colorectal cancer in patients using aspirin in 1-15 yr period prior to CRC diagnosis / index date

20. Cumulative exposure to aspirin in 1 to 10 yr period prior to CRC diagnosis / index date

21. Exposure to aspirin in 1 to 10 yr period prior to CRC diagnosis / index date

22. Risk of Colorectal cancer in patients using aspirin in 1-10 yr period prior to CRC diagnosis / index date

23. Conclusions • Patients taking low dose aspirin have a reduced risk of Colorectal cancer • An 18% reduction in risk is evident after more than 7yrs of aspirin use • Effect not consistent with being COX-2 mediated

24. Methodological strengths • Large sample size and representative population • Data electronically collected – unlikely misclassification bias • Data collected before the diagnosis – no recall bias • Excluded prescriptions 12 months prior to cancer diagnosis

25. Baseline characteristics (15 years of data):

26. Comorbidity in CRC cases and controls: