1. Dyspepsia New Approaches To Clinical Management Professor Pali Hungin Professor of Primary Care and General Practice University of Durham UK

2. Therapeutic Options Patient Empowerment

3. Dyspepsia Who should be investigated? The role of H pylori – test and treat? Therapies for dyspepsia

4. “ Dyspepsia ” Gastro-oesophageal reflux disease: 60%+ Non-ulcer dyspepsia: ?20%+ Ulcer dyspepsia: 4% Reflux disease more accurate on clinical grounds but gross overlap!!

5. Test and Treat H pylori prevalence 40%, declining Ulcer rate 4%, variable A worthwhile gamble? Non-ulcer dyspepsia: benefit 1:15 overall

6. Manageable dyspepsia = acid sensitive dyspepsia

7. Locke et al., Gastroenterology 1997;112:1448–56. Prevalence (%) 25–3435–4445–5455–6465–74 Age (years) 40 0 Women: at least weekly episodes Men: at least weekly episodes Prevalence of heartburn or acid regurgitation

8. Prevalence of GERD by age and sex 800 100 200 300 400 500 600 700 900 12-2424-4445-6464-74Age group Females Males El-Serag & Sonnenberg, Gut 1997;41:594-9. Prevalence per 10,000 population

9. Lagergren et al., N Engl J Med 1999;340:825–31. Odds ratio 20 0 None12–3>30 20 Frequency Chronicity 1 5.1 6.3 16.7 1 5.2 16.4 7.5 Heartburn episodes/weekDuration of symptoms (years) Frequency and duration of symptoms Heartburn as a risk factor for oesophageal adenocarcinoma

10. 0 500 1000 1500 2000 2500 3000 3500 4000 79 84 8994 97 Mortality Year Office of National Statistics, 1999. Mortality due to oesophageal adenocarcinoma in England and Wales

11. Typical symptoms (Heartburn/regurgitation) Atypical symptoms Complications With oesophagitis Without oesophagitis Chest pain (visceral hyperalgesia) Asthma, chronic cough, wheezing Hoarseness (‘reflux laryngitis’) Oesophageal erosions and/or ulcers Stricture Barrett’s oesophagus Oesophageal adenocarcinoma Dental erosions Nathoo, Int J Clin Pract 2001;55:465–9. Range of presentations of GERD

12. “ If I had known I was going to live this long I would have taken better care of myself! ” George Burns at age 95

13. GERD in the older patient. Findings Presence of heartburn does not correlate as well with acid exposure Poorer correlation with pH testing and endoscopic appearances More severe pathology despite equal or less severe/frequent symptoms than younger patients

14. Oesophageal stricture Barrett’s oesophagus Oesophageal adenocarcinoma Anaemia Savary-Miller Grade IV and above Nathoo, Int J Clin Pract 2001;55:465–9. Consequences of severe and prolonged GERD

15. GERD: presentation in the older patient Common Often less severe and less frequent symptoms Dysphagia, vomiting and anaemia more common

16. Medications associated with GERD Affecting LES pressure: Anticholinergics, theophyllines, sedatives, calcium channel blockers Direct injury to oesophagus: Potassium tablets, doxycycline, ferrous sulphate, alendronate, NSAIDs Jasperson. Drug Safety 2002.

17. Management Basic principles 1. Effective symptom relief 2. Earlier detection of serious lesions 3. Prevention of complications

18. The earlier detection of lesions Early investigation New presentations Alteration in symptoms or response to therapy Alarm symptoms

19. PPIsH 2 RAs Lifestyle modifications Prokinetic motility agents Antacids and alginates Surgery Hatlebakk & Berstad, Clin Pharmacokinet 1996;31:386–406. Approaches Treatment options

20. Alginates … Superior to antacids Are not antacids! Do not interact adversely with PPIs Fast relief Can be used for “ topping up ”

21. Acid suppression therapy 1. Empirical therapy or only post-investigation? 2. H 2 -receptor blockers 3. PPIs Old patients may require greater acid suppression to heal oesophagitis

22. Fast relief but longer duration of action than antacids Associated with more drug interactions H 2 RAs are generally not as effective as PPIs for symptom relief or healing Are available as a combination with antacid: quick action and PRN use possible de Caestecker, BMJ 2001;323:736–9. Sonnenberg, Pharmacoeconomics 2000;17:391–401. H 2 -receptor antagonists (H 2 RAs)

23. Risk ratio.012003183.3135 Study % Weight Risk ratio (95% CI) 0.26 (0.15,0.46) Bardhan 1995 5.0 0.33 (0.16,0.69) Klinkenberg-Knol 1987 3.3 0.42 (0.28,0.62) Havelund 1988* 7.1 0.48 (0.33,0.69) Sandmark 1988 7.8 0.59 (0.48,0.73) Bate 1990 11.1 0.60 (0.37,0.98) Dehn 1990* 5.9 0.63 (0.42,0.94) Bianchi Porro 1992 7.1 0.72 (0.54,0.95) Koop 1995 9.5 0.61 (0.38,0.99) IROSG 1991 5.9 0.37 (0.24,0.57) Robinson 1995 6.6 0.26 (0.10,0.67) Vantrappen 1988* 2.2 0.64 (0.52,0.79) Farley 2000 11.0 0.35 (0.21,0.59) Jansen 1999 5.5 0.59 (0.29,1.20) Armbrecht 1997 3.5 0.52 (0.36,0.76) Van Zyl 2000 7.6 0.09 (0.01,0.62) Soga 1999 0.6 0.50 (0.43,0.58) Overall (95% CI) Favours PPIFavours H 2 RAs Favours H 2 RAs Moayyedi. Health Care Needs Assessment 2002. Meta-analysis of PPIs vs H 2 RAs in oesophagitis

24. Acid Suppression Therapy: the realities Investigate all older patients with heartburn symptoms? How practical? Who should be investigated? Is empirical therapy acceptable in those without alarm symptoms? What is pragmatic practice in Primary Care?

25. PPIs: empirical use 133 patients with upper GI cancer. PPI use vs no-PPI prior to investigation: 22/62 vs 1/54  normal endoscopy 747 patients with upper GI cancer. Patients on empirical AST were referred later Time to diagnosis 44 weeks vs 17 weeks Empirical PPI use associated with delayed diagnosis of cancer but not with staging of tumour or outcome Bramble, Suvakovic, Hungin. Gut 1999. Panter, Bramble, O ’ Flanagan, Hungin. Gastroenterol (Ab) 2002.

26. Long Term PPIs and H pylori Should you check the H pylori status? >1% of UK population on long term PPIs! Maastricht 2000: eradication recommended – potential risk of extension of atrophic changes Malfertheiner et al., Aliment Pharmcol Ther 2002.

27. PPIs and interactions Inhibition of cytochrome P450 enzyme system Benzodiazepines, phenytoin, theophyllines, Ca channel blockers Watch for INR control in those on warfarin! Hungin, Rubin, O ’ Flanagan. Postgrad Med J 1999.

28. Therapy: the shorthand to the new approach … Why investigate? Treat symptoms – watch for alarm factors! Likely need for long term, recurrent treatment Do you agree with this? Patients without alarm symptoms unlikely to have a serious problem Empower patients to self manage?

29. Empowerment, Enablement, Education Understanding the problem Understanding the reasons for the consultation Developing a solution that suits the patient

30. Why has the patient consulted? Health and health seeking behaviour Differences between consulters and non- consulters Lydeard S, Jones R. Br J Gen Pract.

31. Health and health seeking behaviour High vs low monitors High vs low blunters

32. PPI use by patients Established repeat prescriptions 1 year or more <6 prescriptions per year 16% 6-9 prescriptions 27% 12 prescriptions 21% 80% of patients used PPIs intermittently! Hungin, Rubin, O ’ Flanagan. Br J Gren Pract 1999.

33. Intermittent PPI use: reasons “ I prefer to take the treatment only when I want to ” “ Only if my symptoms are a problem ” “ Depends on how severe the symptoms are ” “ My body might become used to the treatment ” “ Fear of side effects ” “ Not sure how it works …” Symptoms and Personal Factors Hungin, Rubin, O ’ Flanagan. Br J Gren Pract 1999.

34. Solutions to match patients ’ aspirations … Self medication where safe (nearly always!) Prescribed therapies OTC products Pharmacist ’ s advice

35. SYMPTOMS Severe, frequent, or prolonged (regularly exceeding 4 weeks’ duration) Physician evaluated Symptoms persist for periods greater than 4 weeks Classic episodic symptoms of heartburn and regurgitation, not exceeding 4 weeks’ duration and without alarm features Recommend OTC therapy with antacid, H 2 RA, or H 2 RA/antacid combination Symptomscontrolled PPI therapy treatment dose Alarm or severe symptoms present Alarm or severe symptoms absent Symptoms persist PPI therapy trial high dose (bid) Symptoms persist Maintain therapy with review, watching out for signs of change in symptom pattern Referral to gastroenterologist for further evaluation and/or EGD Symptomscontrolled Symptoms partially respond Algorithm for the treatment of patients with heartburn

36. Dyspepsia: coping with a common problem Nurse-led self management clinics Pharmacist-led management

37. Summary 1. Common, with a low overall risk of significant lesions 2. Symptoms less pronounced in the elderly but more serious consequences 3. Investigation for the earlier detection of lesions? What role empirical therapy? 4. Management: effective acid suppression in those who warrant it; alternative therapies available! 5. Consultation behaviour: empowerment is a powerful tool! 6. New, out of the box approaches