• Arrange emergency admission for anyone with dyspepsia and significant gastrointestinal bleeding.
• Assess people with dyspepsia for alarm features.
• For people with alarm features:
• Refer for endoscopy within 14 days.
• Review and manage drugs known to increase the risk of gastrointestinal bleeding or exacerbate dyspepsia.
• Review and manage lifestyle factors known to exacerbate dyspepsia.
• Prescribe either an alginate or an antacid for symptomatic relief of dyspepsia.
• For people with dyspepsia without alarm features:
• Do a full blood count if there are any features of anaemia.
• Review and manage drugs known to increase the risk of gastrointestinal bleeding or exacerbate dyspepsia.
• Review and manage lifestyle factors known to exacerbate dyspepsia.
• Prescribe, or advise the use of, an antacid or alginate for immediate relief of dyspepsia as required.
• Prescribe additional drug treatment to settle persistent symptoms.
• Step 1: depending on personal preference, treat with either a proton pump inhibitor (PPI) at full dose for 1 month, or test and treat for Helicobacter pylori.
• Step 2: for people who have not responded to a PPI, test and treat for H. pylori. For people who have not responded to treatment for H. pylori, treat with a PPI for 1 month.
• Step 3: for people responding to neither a PPI nor treatment for H. pylori, prescribe either a prokinetic (domperidone, metoclopramide) or an H2-receptor antagonist for 1 month.
• Refer those people not responding to all three treatment steps to secondary care for further management.
• Prescribe maintenance treatment if dyspepsia recurs following treatment.
• For people with dyspepsia without alarm features, and taking nonsteroidal anti-inflammatory drugs (NSAIDs):
• Do a full blood count if there are any features of anaemia.
• Review and manage lifestyle factors manage lifestyle factors known to exacerbate dyspepsia.
• Prescribe, or advise the use of, an antacid or alginate for immediate relief of dyspepsia as required.
• Stop the NSAID if possible, and prescribe a proton pump inhibitor (PPI) for 1 month, and review.
• When it is not possible to stop the NSAID, prescribe a full-dose PPI for 1 month, then maintain at a dose appropriate to the risk of gastrointestinal bleeding. Test for, and eradicate (if present), H. pylori. Reduce NSAID use if possible.
• Refer those people whose symptoms persist despite treatment.

For the purpose of this CKS topic, alarm features are defined as:

• Dyspepsia with one or more of the following:
• Chronic gastrointestinal bleeding.
• Progressive unintentional weight loss.
• Progressive difficulty swallowing.
• Persistent vomiting.
• Iron deficiency anaemia.
• Epigastric mass.
• Suspicion of cancer after investigation with a barium meal.
• People over 55 years of age with persistent or unexplained dyspepsia.

• These recommendations for when to refer for endoscopy conform with guidance issued by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2005]. They are based upon evidence, summarized by NICE, of the sensitivity of clinical features to detect cancer. Approximately 4% of people with these features will have gastric cancer.

• For people with dyspepsia and significant acute gastrointestinal bleeding, arrange immediate admission to hospital.
• For all other people with dyspepsia and alarm features:
• Arrange endoscopy within 14 days and do a full blood count.
• Suspend nonsteroidal anti-inflammatory drugs while awaiting referral. Offer alternative analgesics (e.g. paracetamol and/or opioids).
• The management of other drugs will depend on clinical judgement of the benefits and risks of continued treatment. When there is uncertainty seek specialist advice. Management options include:
• Stopping the drug.
• Reducing the frequency or dose of the drug.
• Substituting the drug for one less likely to cause bleeding or dyspepsia.
• Review and manage lifestyle factors known to exacerbate dyspepsia.
• Prescribe either an alginate or an antacid to relieve dyspepsia whilst awaiting endoscopy. Ensure that proton pump inhibitors or H₂-receptor antagonists (including those obtained over-the-counter) are not used, for a minimum of 2 weeks, before endoscopy.
• Advise those people who deteriorate significantly to seek medical attention.

• Examples of common drugs known to cause gastrointestinal bleeding include:
• Nonsteroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac, naproxen, indometacin).
• Antiplatelet drugs (e.g. aspirin, clopidogrel).
• Anticoagulants (e.g. warfarin).
• Corticosteroids (e.g. prednisolone).

These recommendations conform with those issued by the National Institute for Health and Clinical Excellence (NICE), covering the management of dyspepsia, and referral guidelines for suspected cancer [NICE, 2005; NICE, 2005].

• Basis for arranging endoscopy within 14 days for people with alarm features:
• These recommendations are based upon evidence summarized by NICE for the sensitivity of alarm features for identifying people at risk of having an upper gastrointestinal cancer [NICE, 2005; NICE, 2005].
• Basis for prescribing an alginate or an antacid to relieve the symptoms of dyspepsia while awaiting endoscopy:
• Experts recommend treatment with alginates or antacids for dyspepsia while awaiting endoscopy because they help to relieve symptoms but do not mask malignant ulceration [NICE, 2005]. However, although commonly prescribed, the evidence for antacids and alginates are poor and lacking. Evidence indicates alginate preparations are more effective than placebo in relieving symptoms of gastro-oesophageal reflux.
• Basis for managing drugs known to increase the risk of gastrointestinal (GI) bleeding or exacerbate dyspepsia: experts recommend reviewing all medications known to increase risk of GI bleeds or exacerbate dyspepsia [NICE, 2005]. Options for the management of drugs known to exacerbate dyspepsia and GI bleeds are provided by CKS. These are pragmatic recommendations based upon clinical experience.

• For people with dyspepsia and significant acute gastrointestinal bleeding, arrange immediate admission to hospital.
• For other people with dyspepsia without alarm features who are not taking a nonsteroidal anti-inflammatory drug (NSAID):
• Do a full blood count if there are any features of anaemia.
• Review and manage drugs known to increase the risk of gastrointestinal bleeding or exacerbate dyspepsia.
• Review and manage lifestyle factors known to exacerbate dyspepsia.
• Prescribe, or advise the use of, an antacid or alginate as required for immediate relief of dyspepsia. Prescribe an alginate if symptoms of gastro-oesophageal reflux are present.
• Prescribe additional drug treatment to settle persistent symptoms:
• Step 1: depending on personal preference, treat with either a proton pump inhibitor (PPI) at full dose for 1 month, or test and treat for Helicobacter pylori.
• Step 2: for people who have not responded to a PPI, test and treat for H. pylori. For people who have not responded to treatment for H. pylori, treat with a PPI for 1 month.
• Step 3: for people responding to neither a PPI nor treatment for H. pylori, prescribe either a prokinetic (domperidone, metoclopramide) or an H2-receptor antagonist for 1 month.
• Refer those people not responding to all three treatment steps to secondary care for further management.
• For people with recurrent dyspepsia following successful treatment with either an acid suppressing drug or a prokinetic, restart and maintain the treatment but:
• Prescribe the lowest dose that controls symptoms.
• Advise using the treatment on an as required basis when possible.
• Review maintenance treatment at least annually.

These recommendations conform with those made by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2005].

• Basis for doing a full blood count (FBC): experts recommend checking the FBC because, in a person with dyspepsia, iron deficiency anaemia is a risk factor for cancer.
• Basis for recommending empirical treatment for dyspepsia in people who do not have alarm features: evidence from randomized controlled trials found no difference in outcomes when empirical treatment was compared to endoscopically-guided treatment. NICE considers both H. pylori eradication ('test and treat') and acid suppression to be equally valid empirical treatment options as evidence indicates both strategies to be equally cost-effective.
• H₂-receptor antagonists (H₂RAs) and prokinetics are less preferred for the initial treatment of dyspepsia. Comparative studies from a systematic study found proton pump inhibitors (PPIs) to be more effective than H₂RAs in improving symptoms of dyspepsia. Evidence for prokinetics is sparse [NICE, 2005].
• Basis for maintenance treatment and annual review: NICE found little evidence to guide the long term management of patients who are suffering from chronic, persistent dyspepsia. The recommendations are extrapolated from short-term trials, epidemiological evidence and the consensus view of the guideline development group [North of England Dyspepsia Guideline Development Group, 2004]. Periodic medication review is recommended as good clinical practice. Although there is no evidence for the optimal period, NICE recommends the review should occur once a year as a minimum.

• For people with dyspepsia and significant acute gastrointestinal bleeding, arrange immediate admission to hospital.
• For people with nonsteroidal anti-inflammatory drug (NSAID)-induced dyspepsia without alarm features:
• Do a full blood count if there are any features of anaemia.
• Prescribe, or advise the use of, an antacid or alginate for immediate relief of dyspepsia as required.
• Review and manage lifestyle factors known to exacerbate dyspepsia.
• Review and manage drugs (other than NSAIDs) known to increase the risk of gastrointestinal bleeding or exacerbate dyspepsia.
• Stop the NSAID if acceptable, and prescribe a proton pump inhibitor (PPI) for 1 month. Test and treat for Helicobacter pylori if symptoms recur.
• Offer alternative analgesia (e.g. paracetamol and/or opioids).
• When it is not acceptable to stop the NSAID:
• Prescribe a full-dose PPI for 1 month, and maintain treatment at a dose appropriate to the risk of gastrointestinal bleeding.
• Test and treat for H. pylori (if present).
• If possible, reduce the risk from NSAID use by reducing the frequency or dose of the NSAID or, substituting it for one less likely to cause gastrointestinal symptoms.
• Refer those people whose symptoms persist despite treatment.

• Table 1 shows the categorization of the gastrointestinal safety of various nonsteroidal anti-inflammatory drugs (NSAIDs) [CSM, 2002].

• Stopping NSAIDs when possible: this is a pragmatic recommendation widely supported by experts [NICE, 2005].
• Maintenance treatment with a PPI to reduce the risk of recurrence of dyspepsia for people who continue to use NSAIDs: these recommendations are based upon evidence for the efficacy of PPIs at reducing the risk of dyspepsia in those taking a NSAID.
• Testing for Helicobacter pylori in people prescribed a PPI long term: these recommendations are based upon expert opinion (50 experts from 26 countries) published in the Maastrict Consensus Report [Malfertheiner et al, 2007]. They concluded that although there is a lack of evidence to support the treatment of H. pylori in people taking long-term PPIs, testing and treatment for H pylori is recommended because:
• It may reduce the risk of atrophic gastritis.
• It may reduce the risk of gastric cancer.

• The management of drugs, other than nonsteroidal anti-inflammatory drugs (NSAIDs), that are known to increase the risk from gastrointestinal bleeding, dyspepsia, or ulceration (including those in Table 1) will depend on clinical judgement of the benefits and risks of continued treatment. When there is doubt seek specialist advice. Management options include:
• Stopping the drug.
• Reducing the frequency or dose of the drug.
• Substituting the drug for one less likely to cause bleeding or dyspepsia.
• Continuing the drug and prescribing a gastroprotective agent.

• Table 1 gives examples of common drugs known to cause gastrointestinal (GI) bleeding, dyspepsia, or ulceration.

• Experts recommend reviewing all medications known to exacerbate dyspepsia [NICE, 2005].
• Drugs included in Table 1 are known to exacerbate dyspepsia or increase the risk of gastrointestinal (GI) bleeds [Talley et al, 2001; North of England Dyspepsia Guideline Development Group, 2004; Pirmohamed et al, 2004; Paton and Ferrier, 2005; MeReC, 2007].
• Options for the management of drugs known to exacerbate dyspepsia and GI bleeds are provided by CKS. These are pragmatic recommendations based upon clinical experience.

• Advise people with dyspepsia that symptoms may be improved if they:
• Lose weight (if they are overweight).
• Stop or reduce smoking (if they are a smoker).
• Stop or reduce alcohol consumption.
• Stop or reduce intake of any food or drink associated with worsening symptoms.
• Advise people with reflux symptoms when lying down to:
• Avoid having meals within 3–4 hours of going to bed.
• Raise the height of the head of the bed by a few inches.

• These recommendations for lifestyle interventions to control dyspepsia conform with those made by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2005]. Limited evidence summarized by NICE found:
• Obesity to be a significant but small risk factor for gastro-oesophageal reflux disease.
• Insufficient evidence that other factors are a significant risk in the development of gastro-oesophageal reflux disease, peptic ulcer disease, or non-ulcer dyspepsia.
• NICE concluded that although there is a lack of evidence for the role of lifestyle factors having a significant effect on the development of conditions resulting in dyspepsia, it is pragmatic to advise people to avoid factors that are commonly known to exacerbate dyspepsia.

• For people who have not previously been diagnosed with Helicobacter pylori infection, test with:
• Urea breath test (unless they have received a proton pump inhibitor [PPI] in the past 14 days or an antibiotic in the past 28 days), or
• Stool antigen test (unless they have received a PPI in the past 14 days or an antibiotic in the past 28 days), or
• Laboratory serology testing (where the performance of the test has been locally validated).
• For people who have been previously diagnosed with H. pylori infection and treated with eradication therapy, re-test (if indicated) at least four weeks after treatment. Urea breath test is preferred. However, stool antigen test could be used if urea breath test is not available.
• Stop PPI use 14 days prior to testing. Withhold testing for 28 days after treatment with an antibiotic.

• These recommendations are based on those issued by the National Institute for Health and Clinical Excellence (NICE) [North of England Dyspepsia Guideline Development Group, 2004], the British National Formulary (BNF) [BNF 55, 2008] and the Maastricht III Consensus report (based on expert opinion [50 experts from 26 countries] and published evidence) issued by the European Helicobacter Study Group (EHSG) [Malfertheiner et al, 2007].
• For people who have not previously been diagnosed with Helicobacter pylori infection, all three tests may be used:
• Evidence summarized by NICE show that the sensitivity of stool antigen testing, breath testing, and some serological tests to be over 90% [North of England Dyspepsia Guideline Development Group, 2004].
• NICE considered this level of sensitivity adequate to recommend the use of these tests for detecting H. pylori infection.
• For carbon urea breath test and stool antigen test, proton pump inhibitors should be stopped for at least two weeks before the test while any antibiotics must be stopped four weeks before [McNulty et al, 2005; BNF 55, 2008].
• One systematic review found evidence that PPI treatment can reduce accuracy of stool antigen test and urea breath test [Gisbert and Pajares, 2004]. The negative effect of PPIs disappeared one to two weeks after stopping the PPI.
• Re-testing for H. pylori after eradication therapy:
• If re-testing is indicated, NICE recommends that the carbon urea breath test should be used as it found insufficient evidence to recommend the stool antigen test as a test of eradication [NICE, 2005].
• The carbon urea breath test is also preferred by EHSG (as detailed in the Maastricht III Consensus report) based on assessment of the evidence which found the accuracy of the stool antigen tests to be less than that of the urea breath test in people re-tested after H. pylori eradication [Malfertheiner et al, 2007]. Nevertheless, expert consensus considered that the stool antigen test can be used if the carbon urea breath test is not available. They also recommended that retesting should be done at least four weeks after eradication treatment.

• Prescribe a 7-day triple-therapy regimen with twice-daily dosing (see Table 1). Preferred regimens are:
• Amoxicillin 1 g plus clarithromycin 500 mg plus either lansoprazole 30 mg or omeprazole 20 mg (all taken twice daily), or
• Clarithromycin 250 mg plus metronidazole 400 mg plus either lansoprazole 30 mg or omeprazole 20 mg (all taken twice daily).
• Other proton pump inhibitors can be used, but they are considerably more expensive (see Table 1 for dose).
• Avoid amoxicillin-containing regimens for those with known or suspected penicillin allergy.
• Check for recent use of clarithromycin or metronidazole; this may promote resistance, resulting in eradication failure:
• For those recently treated with clarithromycin (up to one year) for any infection, choose a regimen containing amoxicillin and metronidazole.
• For those recently treated with metronidazole (up to one year) for any infection, choose a regimen containing amoxicillin and clarithromycin.
• For people who require a second course of eradication therapy, choose a regimen that does not include antibiotics given previously.

• Table 1 shows the options for triple therapy for eradication of Helicobacter pylori.
• The individual components must be prescribed separately, as no proprietary triple-therapy product is available. Both Heliclear^® and Helimet^® have been discontinued in the UK.
• For eradication failure, the British National Formulary recommends [BNF 55, 2008]:
• A 2-week regimen comprising a proton pump inhibitor plus tripotassium dicitratobismuthate (De-Noltab^®) 240 mg twice daily, plus tetracycline 500 mg four times daily, plus metronidazole 400 mg three times daily.
• Alternatively, if the person has been referred for endoscopy, treatment will be based on the results of culture and sensitivity testing.

• These recommendations are based on those issued by the National Institute for Health and Clinical Excellence (NICE), the Health Protection Agency and the British National Formulary [NICE, 2005; BNF 55, 2008; HPA, 2008].
• NICE recommends both clarithromycin-amoxicillin-proton pump inhibitor (PPI) and clarithromycin-metronidazole-PPI regimens as valid first-line therapies. This is supported by the Health Protection Agency [HPA, 2008]:
• Eradication is effective in 80–85% of people. Evidence from randomized controlled trials found both regimens to be equally effective, and better than the amoxicillin-metronidazole-PPI regimen.
• Choice of PPI:
• NICE does not recommend any particular PPI for use in triple therapies [NICE, 2005].
• Little evidence is available to support the use of one PPI over another. Evidence from meta-analyses found omeprazole and lansoprazole to be equally effective and as effective as other PPIs.
• Omeprazole and lansoprazole are considerably cheaper than other PPIs and are therefore recommended by CKS.
• The recommendation to avoid antibiotics which have been recently used is based on advice issued by the British National Formulary [BNF 55, 2008] and by the NICE guidance development group [North of England Dyspepsia Guideline Development Group, 2004]. However, there is uncertainty regarding how long these antibiotics should be avoided if they have been previously used for other infections.
• The NICE guidance development group identified advice which states that 'GPs should not use clarithromycin or metronidazole if the person has received this for any infection in the past year, as monotherapy with these agents very readily lead to resistance' [North of England Dyspepsia Guideline Development Group, 2004].
• The BNF does not provide any information regarding how long these antibiotics should be avoided if they have been used for other infections [BNF 55, 2008].