Risk of colorectal cancer in patients taking statins and NSAIDS

1. Risk of colorectal cancer in patients taking statins and NSAIDS Dr Yana Vinogradova, Prof Julia Hippisley-Cox, Dr Carol Coupland and Prof Richard Logan Divisions of Primary Care, and Epidemiology & Public Health, University of Nottingham, UK UEGW Plenary session Berlin 23rd October 2006

2. Background to CRC statin analysis • Evidence from animal models and other lab data that statins might prevent cancer • A meta-analysis of 26 large statin trials found no difference in incidence of CRC but limited power as only 4 reported CRC data • Recent case control study (Poynter NEJM 2005) found a 47% reduction in CRC risk

3. Meanwhile • Mass of observational and experimental evidence that aspirin and traditional NSAIDs lower CRC risk • Trials of Colorectal adenoma prevention with COX2 show a 40-50% reduction in recurrence (Bertagnolli, Arber NEJM August 2006) • Little observational data available on risk of colorectal cancer in COX2 users

4. Study population: QRESEARCH database • Currently largest primary care database in the UK • 537 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

5. General Practice data collection:

6. 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

7. Study design & setting • Nested case control study • Study period Jan 1995-July 2005 • Cases were incident colorectal cancer patients • 5 controls matched by • Age • Sex • Practice • Calendar year

8. Exposure assessment : • statins, NSAIDs, Cox2 Inhibitors and aspirinprescriptions analysis restricted to subjects with +4yrs of prescribing data • any use: • at least 1 script in 13-48 months prior to the index date (date of diagnosis in the case) • number of prescriptions: • 1 script only • 2-12 scripts • 13-24 scripts • 25 or more scripts

9. Statistical analysis • Conditional logistic regression • Odds ratios + 95% CI • Unadjusted & adjusted

10. Study Sample:

11. Comorbidity in CRC cases and controls:

12. 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 Socio-economic status (Townsend score for post code) quintiles Morbidities IHD (±MI) Diabetes High BP Osteoarthritis Colitis Rheumatoid arthritis Stroke Confounding factors :

13. Any use in 13-48 months prior to the index date

16. Risks with prolonged prescribing in 13-48 months prior to index date • 25 or more statin scripts: adj. OR 1.13 (0.91 - 1.41) • 25 or more COX-2 scripts: adj. OR 0.34 (0.14 - 0.85) • 25 or more NSAID scripts: adj. OR 0.76 (0.60 – 0.95) • 25 or more Aspirin scripts: adj. OR 0.88 (0.74 – 1.05)

17. Conclusions • Prolonged statin use is not associated with reduced risk of colorectal cancer • Prolonged NSAID and Cox2 inhibitor use is associated with reduced risk of colorectal cancer

18. Implications • No increase in risk of colorectal cancer with cholesterol lowering • Supports role for COX 2 inhibitors in secondary / tertiary prevention of colorectal cancer

20. 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

21. Use of individual statins

23. Baseline characteristics:

24. Study sample:

25. Rel Risk of CRC with aspirin use by recency, duration and dose in UK GPRD (Garcia Rodriguez Epidemiology 2001)