Dyspepsia: Management of dyspepsia in adults in primary care

In a recent prospective observational study the prevalence of gastric cancer was 4% in a cohort of patients referred urgently for alarm features. Referral for dysphagia or significant weight loss at any age plus age older than 55 years with alarm symptoms would have detected 99.8% of the cancers found in the cohort. These findings are supported by other retrospective studies.

Retrospective studies have found that cancer is rarely detected in patients younger than 55 years without alarm symptoms and, when found, the cancer is usually inoperable.

In the UK, morbidity (non-trivial adverse events) and mortality rates for upper gastrointestinal endoscopy may be as high as 1 in 200 and 1 in 2000, respectively.

One retrospective study showed that acid suppression therapy could mask or delay the detection of gastric and oesophageal adenocarcinoma.

Patients over 80 years of age are poorly represented in clinical trials and the balance of benefits and risks of treatments and investigations in this group is less certain. However, it is reasonable to assume that they will receive similar benefits in the absence of complicating factors.

Available trials of lifestyle advice to reduce symptoms of dyspepsia are small and inconclusive.

Epidemiological studies show a weak link between obesity and GORD, but no clear association between dyspepsia and other lifestyle factors: smoking, alcohol, coffee and diet. However, individual patients may be helped by lifestyle advice and there may be more general health benefits that make lifestyle advice important.

One possible cause of reflux disease is transient relaxation of the lower oesophageal sphincter. Obesity, smoking, alcohol, coffee and chocolate may cause transient lower oesophageal sphincter relaxations, while fatty foods may delay gastric emptying. Lying flat may increase reflux episodes because gravity does not then prevent acid regurgitation. Thus raising the head of the bed and having a main meal well before going to bed may help some patients.

In patients with non-ulcer dyspepsia, three small trials of psychological interventions showed decreases in dyspeptic symptoms at the end of the intervention at 3 months not persisting to 1 year.

No formal cost-effectiveness analysis has been conducted although (in 2002) British Association for Counselling and Psychotherapy (BACP) accredited counsellors and community-based clinical psychologists cost typically £30 and £67 per hour of patient contact time to which travel, administrative and location costs must be added, net of changes to medication costs.

In primary care, described symptoms are a poor predictor of significant disease or underlying pathology.

Review common elements of care for managing dyspepsia (section 1.3).

PPIs are more effective than antacids at reducing dyspeptic symptoms in trials of patients with uninvestigated dyspepsia. The average rate of response taking antacid was 37% and PPI therapy increased this to 55%: a number needed to treat for one additional responder of six.

PPIs are more effective than H ₂ RAs at reducing dyspeptic symptoms in trials of patients with uninvestigated dyspepsia. The average response rate in H ₂ RA groups was 36% and PPI increased this to 58%: a number needed to treat for one additional responder of five.

Early endoscopy has not been demonstrated to produce better patient outcomes than empirical treatment.

Test and endoscopy has not been demonstrated to produce better patient outcomes than empirical treatment.

H. pylori testing and treatment is more effective than empirical acid suppression at reducing dyspeptic symptoms after 1 year in trials of selected patients testing positive for H. pylori. The average response rate receiving empirical acid suppression was 47% and H. pylori eradication increased this to 60%: a number needed to treat for one additional responder of seven.

H. pylori testing and treatment has not been demonstrated to produce better patient outcomes than endoscopy, although there is considerable variation in study findings. However, studies consistently demonstrate that test and treat dramatically reduces the need for endoscopy and provides significant cost savings.

Evidence is taken from patients with endoscopy-negative reflux disease. Patients using PPI therapy as required (waiting for symptoms to develop before taking treatment) reported similar 'willingness to continue' to those on continuous PPI therapy.

Patients taking therapy as required used about 0.4 tablets per day, averaged across studies of 6–12 months duration. Taking therapy when symptoms occur may help patients to tailor their treatment to their needs.

PPIs are more effective than H ₂ RAs at reducing dyspeptic symptoms in trials of patients with uninvestigated dyspepsia. However, individual patients may respond to H ₂ RA therapy.

In one trial of 1-year duration, patients receiving a PPI or a prokinetic experienced similar time free of symptoms.

Dyspepsia is a remitting and relapsing disease, with symptoms recurring annually in about half of patients.

Available trials of lifestyle advice to reduce symptoms of dyspepsia are small and inconclusive.

Epidemiological studies show a weak link between obesity and GORD, but no clear association between dyspepsia and other lifestyle factors: smoking, alcohol, coffee and diet. However, individual patients may be helped by lifestyle advice and there may be more general health benefits that make lifestyle advice important.

One possible cause of reflux disease is transient relaxation of the lower oesophageal sphincter. Obesity, smoking, alcohol, coffee and chocolate may cause transient lower oesophageal sphincter relaxations, whereas fatty foods delay gastric emptying. Lying flat may increase reflux episodes, because gravity does not then prevent acid regurgitation. Thus, raising the head of the bed and having a main meal well before going to bed may help some patients.

PPIs are more effective than H ₂ RAs at healing oesophagitis in trials. Healing occurred in 22% of patients on placebo, 39% of patients on H ₂ RAs (a number needed to treat of six) and 76% of patients on PPIs (a number needed to treat of two). There is considerable variation in the findings of trials.

In trials, extending treatment to 2 months increased healing of oesophagitis by a further 14%.

If patients have severe oesophagitis and remain symptomatic, double-dose PPI for a further month may increase the healing rate.

Limited evidence shows that antacids are no more effective at healing oesophagitis than placebo.

On balance, PPIs appear more effective than H ₂ RAs in endoscopy-negative reflux disease. In head-to-head trials 53% of patients became symptom-free on PPI compared with 42% receiving H ₂ RAs, although the difference was not statistically significant. The same pattern of benefit is apparent in placebo-controlled trials.

The majority of patients will experience a recurrence of symptoms within 1 year.

PPIs are more effective than H ₂ RAs at maintaining against relapse of oesophagitis in trials of 6–12 months duration. Relapse occurred in 59% of patients on H ₂ RA and 20% of patients on PPI (a number needed to treat of three). There is considerable variation in the findings of trials.

PPIs at full dose are more effective than PPIs at low dose in trials of 6–12 months duration. Relapse of oesophagitis occurred in 28% of patients on low-dose PPI and 15% of patients on full-dose PPI (a number needed to treat of eight). There is considerable variation in the findings of trials.

There are no long-term trials in endoscopy-negative reflux disease. However, the most cost-effective approach appears to be to offer patients intermittent 1-month full-dose or as-required PPI therapy, rather than continuous therapy .

Patients with endoscopy-negative reflux disease and using PPI therapy as required (waiting for symptoms to develop before taking treatment) reported similar 'willingness to continue' to those on continuous PPI therapy.

Patients taking therapy as required used about 0.4 tablets per day, averaged across studies of 6–12 months duration. Taking therapy when symptoms occur may help patients to tailor their treatment to their needs.

PPIs are more effective than H ₂ RAs or prokinetics at reducing dyspeptic symptoms in trials of patients with GORD. However, individual patients may respond to H ₂ RA or prokinetic therapy.

Open surgery is no better than long-term medical therapy at achieving remission from symptoms.

Laparoscopic surgery is no better than open surgery at achieving remission from symptoms.

There is a small (0.1−0.5%) but important post-operative mortality associated with anti-reflux surgery.

In one large randomised controlled trial (RCT) of patients who have had oesophageal stricture, 30% of the PPI group required repeat dilatation compared with 46% of the ranitidine group.

H. pylori eradication therapy increases duodenal ulcer healing in H. pylori-positive patients. After 4–8 weeks, patients receiving acid suppression therapy average 69% healing; eradication increases this by a further 5.4%, a number needed to treat for one patient to benefit from eradication of 18.

H. pylori eradication therapy reduces duodenal ulcer recurrence in H. pylori-positive patients. After 3–12 months, 39% of patients receiving short-term acid suppression therapy are without ulcer; eradication increases this by a further 52%, a number needed to treat for one patient to benefit from eradication of two. Trials all show a positive benefit for H. pylori eradication but the size of the effect is inconsistent.

H. pylori eradication therapy does not increase gastric ulcer healing in H. pylori-positive patients, when compared with acid suppression alone in trials of 4–8 weeks duration.

H. pylori eradication therapy reduces gastric ulcer recurrence in H. pylori-positive patients. After 3–12 months, 45% of patients receiving short-term acid suppression therapy are without ulcer; eradication increases this by a further 32%, a number needed to treat for one patient to benefit from eradication of three. Trials all show a positive benefit for H. pylori eradication but the size of the effect is inconsistent.

H. pylori eradication therapy is a cost-effective treatment for H. pylori-positive patients with peptic ulcer disease. Eradication therapy provides additional time free from dyspepsia at acceptable cost in conservative models and is cost-saving in more optimistic models.

In patients using NSAIDs with peptic ulcer, H. pylori eradication does not increase healing when compared with acid suppression therapy alone in trials of 8 weeks duration.

In patients using NSAIDs with previous peptic ulcer, H. pylori eradication reduces recurrence of peptic ulcer. In a single trial of 6 months duration, recurrence was reduced from 18% to 10%.

In patients using NSAIDs without peptic ulcer disease, H. pylori eradication reduces the risk of a first occurrence of peptic ulcer. In a single trial of 8 weeks duration, first occurrence was reduced from 26% to 7% of patients.

See also evidence statements for eradicating H. pylori in peptic ulcer disease (see above).

Full-dose PPI therapy heals peptic ulcers in the majority of cases.

The risk of serious ulcer disease leading to hospitalisation associated with NSAID use is of the order of one hospitalisation per 100 patient-years of use in unselected patients. However, patients with previous ulceration are at higher risk.

NSAID use is associated with increased risks of gastrointestinal bleeding in unselected patients, approximately five-fold for musculoskeletal pain and twofold for secondary prevention of cardiovascular disease with low-dose aspirin.

In patients using NSAIDs without peptic ulcer disease, double-dose H ₂ RA therapy or PPIs significantly reduce the incidence of endoscopically detected lesions.

In patients using NSAIDs without peptic ulcer disease, misoprostol at low dose is less effective than PPIs at reducing the incidence of endoscopically detected lesions, and has greater side-effects.

In patients using NSAIDs without peptic ulcer disease, substitution to a Cox2-selective NSAID is associated with a lower incidence of endoscopically detected lesions. The promotion of healing and prevention of recurrence in those with existing ulcer disease is unclear.

Evidence is taken from patients with endoscopy-negative reflux disease. Patients using PPI therapy as required (waiting for symptoms to develop before taking treatment) reported similar 'willingness to continue' to those on continuous PPI therapy.

Patients taking therapy as required used about 0.4 tablets per day, averaged across studies of 6–12 months duration. Taking therapy when symptoms occur may help patients to tailor their treatment to their needs.

Symptoms will naturally improve in 36% of patients; 7% will improve due to eradication therapy but 57% of substantial symptoms will remain over a 3–12 month period.

The effect of repeated eradication therapy on H. pylori status or dyspepsia symptoms in non-ulcer dyspepsia is unknown.

Full-dose PPIs are no more effective than maintenance or low-dose PPIs in the management of non-ulcer dyspepsia but are more costly to prescribe (on average: £29.50 versus £15.40 per month).

Low-dose PPIs are more expensive to prescribe than H ₂ RAs (on average: £15.40 versus £9.50 per month), although the evidence supporting PPIs is stronger.

If PPIs or H ₂ RAs provide inadequate symptomatic relief, offer a trial of a prokinetic.

Evidence is taken from patients with endoscopy-negative reflux disease. Patients using PPI therapy as required (waiting for symptoms to develop before taking treatment) reported similar 'willingness to continue' to those on continuous PPI therapy.

Patients taking therapy as required used about 0.4 tablets per day, averaged across studies of 6–12 months duration. Taking therapy when symptoms occur may help patients to tailor their treatment to their needs.

Antacid therapy is no more effective than placebo in reducing the symptoms of non-ulcer dyspepsia.

Evidence from evaluations of diagnostic test accuracy show that serological testing (sensitivity 92%, specificity 83%) performs less well than breath testing (sensitivity 95%, specificity 96%) and stool antigen testing (sensitivity 95%, specificity 94%). The resultant lower positive predictive value^[7] (64% vs. 88% or 84%, respectively) leads to concerns about the unnecessary use of antibiotics when serology testing is used.

Although some serological tests have been shown to perform at above 90% sensitivity and specificity, it is incorrect to assume that this will apply in all localities.

Eradication is effective in 80–85% of patients.

Eradication may reduce the long-term reduced risk of ulcer and gastric cancer.

Clarithromycin 250 mg twice-daily is as effective as 500 mg twice-daily when combined with metronidazole.

PPI, amoxicillin, clarithromycin 500 mg (PAC ₅₀₀ ) regimens and PPI, metronidazole, clarithromycin 250 mg (PMC ₂₅₀ ) regimens achieve the same eradication rate.

PMC ₂₅₀ used as a first-line therapy may induce resistance to both clarithromycin and metronidazole, whereas amoxicillin resistance does not seem to increase after use of a PAC regimen.

Per course of treatment PAC ₅₀₀ costs about £36, while PMC ₂₅₀ costs £25.

Although 14-day therapy gives an almost 10% higher eradication rate, the absolute benefit of H. pylori therapy is relatively modest in non-ulcer dyspepsia and undiagnosed dyspepsia and the longer duration of therapy does not appear cost-effective.

In patients with peptic ulcer, increasing the course to 14 days duration improves the effectiveness of eradication by nearly 10% but does not appear cost-effective.