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Modern diagnosis and management of dyspepsia

Brendan Delaney
MD FRCP MRCGP
Reader
Department of Primary Care and General Practice
University of Birmingham

The definition of dyspepsia is based on clinical features rather than pathophysiology, and dyspeptic symptoms may be indicative of a variety of underlying pathologies. Causes include oesophagitis, peptic ulcers, drug adverse effects and upper gastrointestinal malignancy. The majority of patients have no significant abnormality to account for their symptoms and are said to have non-ulcer or "functional" dyspepsia.
NHS spending on managing dyspepsia exceeded £1.1b in 1998. Research has centred around the cost-effectiveness of initial management strategies for dyspepsia, treatments for non-ulcer dyspepsia and the definition of dyspepsia itself, in an attempt to use expensive treatments and investigations in a more rational fashion.

Definition of dyspepsia
The working party classification of 1988 defined dyspepsia as any symptom referable to the upper gastrointestinal tract. In 1991 a consensus meeting in Rome excluded patients with heartburn or acid reflux as their only symptom.(1) In 1999 these "Rome-I criteria" were revised.(2) The "Rome-II criteria" state that patients need to have "predominant" pain or discomfort centred in the upper abdomen to be classified as having dyspepsia. Patients with predominant heartburn or acid reflux are classed as having gastro-oesophageal reflux disease (GORD), and patients with bloating and relief of symptoms by evacuation as irritable bowel syndrome (IBS).
These new definitions have not yet been tested, particularly in primary care where the majority of patients have both epigastric pain and heartburn. However, the consideration of important differential diagnoses such as GORD and IBS is important in primary care. Whether "predominant heartburn" can satisfactorily exclude peptic ulcer is an important research question, as previous studies have shown that as many peptic ulcer patients report heartburn as epigastric pain.(3)

Managing dyspepsia
A number of strategies for managing dyspeptic patients, incorporating non-invasive tests for Helicobacter pylori followed by either endoscopy or H. pylori eradication therapy restricted to those testing positive, have been suggested.

Initial endoscopy
Rather than empirical acid suppression, an alternative strategy is to investigate all dyspeptic patients before initiating a prescription. Patients over the age of 50 with dyspepsia may have an underlying upper gastrointestinal cancer. Those over the age of 55 with recent onset of symptoms or constant pain, and all those patients with symptoms suggestive of malignancy (weight loss, dysphagia, early satiety, jaundice or anaemia), should be investigated by prompt endoscopy under recent NHS guidelines for the prompt investigation of patients with suspected cancer.(4)
A meta-analysis of four prospective randomised studies has indicated that early endoscopy as a strategy may also be more effective in terms of cure of dyspeptic symptoms than empirical antacid therapy (relative risk of 0.88, 95% confidence interval 0.77-1.00 for dyspepsia, initial endoscopy compared with empirical acid suppression). Initial endoscopy is associated with additional cost.
One primary care-based randomised controlled trial (RCT) has examined the cost-effectiveness of initial endoscopy compared with usual management.(5) The cost per patient free of symptoms was £1,728 at a baseline cost of endoscopy of £246. A sensitivity analysis showed that, if the cost of endoscopy could fall to £100, this would fall to only £165 per patient free of symptoms at one year. The implication is that innovative means of reducing the cost of open-access gastroscopy should be explored.

Non-invasive H. pylori testing and eradication
Two trials comparing test-and-eradicate with endoscopy in secondary care have been conducted. One found that H. pylori eradication was more effective than endoscopy in reducing dyspeptic symptoms in patients under the age of 45 years.(6) One year later, 57% of the "test and treat" group had dyspepsia, compared with 70% of the endoscopy group (relative risk of 0.81, 95% confidence interval 0.51-1.19).
The other trial randomised 500 patients referred by GPs with uninvestigated dyspepsia for "test and treat" or endoscopy.(7) Symptoms were similar at one year, but the use of endoscopy in the "test and treat" group was 60% less than in the endoscopy group. It would be reasonable to conclude that H. pylori "test and treat" is more cost-effective than endoscopy and at least as effective. It remains to be seen whether "test and treat" is cost-effective as an initial intervention for dyspepsia.

Helicobacter pylori
H. pylori eradication for non-ulcer dyspepsia
In a recent meta-analysis of nine high-quality RCTs, evaluating 2,541 patients, H. pylori eradication was associated with a 9% (4-14%) relative risk reduction; an NNT (number needed to treat) of 15 (95% confidence interval 11-131) was calculated, based on a control event rate of 71% at one year.(8) It is possible that the effect of H. pylori eradication in non-ulcerative dyspepsia is based on a subgroup of patients with an "ulcer diathesis", where the treatment prevents the development of future peptic ulcers. This hypothesis is difficult to prove but provides one explanation as to why an effect is seen where no association has been observed between chronic H. pylori gastritis and dyspeptic symptoms.

H. pylori eradication and coronary heart disease
A study has found that coronary heart disease is twice as common in those infected with H. pylori.(9) The causal nature of this relationship has been questioned, but a recent placebo-controlled study (presented in abstract at this year's United European Gastroenterology Week) suggested that H. pylori eradication may prove effective in secondary prevention. A 15% reduction in recurrent cardiac events was observed at one year in 325 acute myocardial infarction patients randomised to eradication therapy or placebo.(10)

Eradication therapies
A diverse array of regimens has been proposed for the eradication of H. pylori. A systematic review has considered the evidence relating to efficacy, adherence and cost.(11) The principal components of cost in an eradication therapy are the duration of treatment, the choice of proton pump inhibitor and dose, and the choice and dose of clarithromycin.
The lowest-dose regimens with eradication rates above 85% are likely to be the most cost-effective. These include omeprazole 20mg bd, amoxycillin 500mg tds and metronidazole 400mg tds, and omeprazole 20mg od, clarithromycin 250mg bd and tinidazole 500mg bd. The cheapest option is amoxycillin-nitroimidazole, but this may be less effective  than clarithromycin-nitroimidazole. The amoxycillin-clarithromycin combination is the most expensive and should be reserved for areas where H. pylori nitroimidazole resistance is high.

References

  1. Talley NJ, Colin-Jones D, Koch KL, Koch M, Nyren O, Stanghellini V. Functional dyspepsia: a classification with guidelines for diagnosis and management. Gastroenterol Int 1991;4(4):145-60.
  2. Rome II: a multinational consensus document on functional gastro-intestinal disorders. Gut 1999; 45 Suppl 2.
  3. Moller HJ, Bytzer P, Schaffalitzky dMO. Management of dyspeptic patients in primary care: value of the unaided clinical diagnosis and of dyspepsia sub-grouping. Scand J Gastroenterol 1998;33(8):799-805.
  4. NHS Executive. Referral guidelines for suspected cancer. Leeds: NHS Executive; 2000.
  5. Delaney BC, Wilson S, Roalfe A, et al. Cost-effectiveness of initial endoscopy for dyspepsia in patients over the age of 50 years: a randomised controlled trial in primary care. Lancet 2000; 356:1965-9.
  6. Heaney A, Collins JSA, Watson RGP, McFarland RJ, Bamford KB, Tham TCK. A prospective randomised trial of a 'test and treat' policy versus endoscopy-based management in young Helicobacter-pylori-positive patients with ulcer-like dyspepsia, referred to a hospital clinic. Gut 1999; 45:186-90.
  7. Lassen AT, Pedersen FM, Bytzer P, Schaffalitzky de Muckadell OB. Helicobacter pylori 'test and eradicate' or prompt endoscopy for management of dyspeptic patients: a randomised controlled trial with one year follow-up. Lancet 2000;356:455-60.
  8. Soo S, Moayyedi P, Deeks J, Delaney BC, et al. Helicobacter pylori eradication for non-ulcer dyspepsia. The Cochrane Library. Oxford: Update Software; 2000.
  9. Danesh J, Youngman L, Clark S, Parish S, Peto R, Collins R (for the ISIS collaborative group). Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling-pairs study. BMJ 1999; 319:1157-62.
  10. Stone A. Does Helicobacter pylori cause heart disease? Gut 2000;47 Suppl III:A29.
  11. Penston JG, McColl KEL. Eradication therapy of Helicobacter pylori: an objective assessment of current therapies. Br J Clin Pharmacol 1997;43:223-43.

Resources
British Society of Gastroenterology
W:www.bsg.org.uk

Primary Care Society for Gastroenterology
W:www.pcsg.org.uk

Health Technology Assessment Programme
W:www.hta.nhsweb.nhs.uk

National Institute for Clinical Excellence
W:www.nice.org.uk

Primary Care National Electronic Library for Health
W:www.nelh-pc.nhs.uk