In the long-term management of patients taking PPIs, the initial indication for prescription always needs review. Persistent symptoms may require further investigation.
Gastro-oesophageal reflux disease
Gastro-oesophageal reflux disease is probably the most frequent indication for prescribing PPIs. For patients with symptoms typical of gastro-oesophageal reflux disease, a therapeutic trial of PPIs can be started as a first step. If symptoms are relieved, this serves to support the diagnosis. After diagnosis, most of the controversy about the management of gastro-oesophageal reflux disease has been about pharmacological therapy. Should treatment be stepped up from the least potent towards the most potent therapy or stepped down from most towards least potent, with the end point being symptom control? This will be guided by the symptoms and, if indicated, endoscopy.
Whether the goal of therapy is symptomatic relief or reduction of adenocarcinoma risk, patients should be informed of the importance of risk factors for symptom generation and adenocarcinoma development. Obesity, smoking, alcohol and fatty foods all exacerbate gastro-oesophageal reflux disease and are risk factors for oesophageal carcinoma.2 While the absolute risk of adenocarcinoma is small, overweight people and obese people have about 1.5 and 4 times the risk of individuals with normal weight. Once lifestyle is addressed, the key questions determining the appropriate use of PPIs are:
- What is the natural history of gastro-oesophageal reflux disease?
- Does long-term treatment reduce complications?
Long-term studies of patients with dyspepsia and gastro-oesophageal reflux disease show that many patients' symptoms resolve and they stop treatment. While PPIs provide more effective symptom control than histamine (H2) receptor antagonists there are also overwhelming long-term data that a substantial proportion of patients can control their symptoms with lifestyle interventions, antacids, H2receptor antagonists or PPIs taken when required.
PPIs should be prescribed regularly when there is a history of oesophageal stricture as, unlike H2receptor antagonists, they reduce stricture recurrence. The elderly also require regular therapy as they are more likely to have severe oesophagitis despite milder non-specific symptoms.3
Long-term PPI therapy is currently recommended for all patients with Barrett's oesophagus although treatment is yet to be shown to reduce the risk of adenocarcinoma. A large randomised trial is investigating if a combination of low-dose aspirin and a PPI may reduce the development of adenocarcinoma in patients with Barrett's oesophagus.4
Gastric and duodenal ulcer disease
In patients who are not taking non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, H. pylori is a key cause of peptic ulcer disease. Its eradication effects a cure. Everyone with a documented history of peptic ulcer disease and evidence of H. pylori infection should therefore be offered eradication therapy rather than be subjected to long-term PPI therapy. PPIs do have some antibacterial activity against H. pylori, but must be used in combination with antibiotics to achieve eradication. This simple and effective strategy is under utilised.
Patients taking long-term NSAIDs who also have H. pylori infection have a six-fold increase in the risk of ulcer bleeding, in contrast to a risk of less than two-fold for patients with H. pylori infection alone and almost five-fold for patients on NSAIDs with no H. pylori infection. The approach to primary prevention of ulcer disease in patients taking long-term NSAID and antiplatelet therapy will depend on clinical circumstances. Serious NSAID-induced gastrointestinal complications occur in about 1.5% of patients per year. This risk increases with the type of NSAID and dosage, concurrent warfarin or antiplatelet therapy, age and a past history of ulcer disease. Patients requiring NSAIDs, aspirin or clopidogrel, who are at increased risk of peptic ulcer complications should be considered for concurrent treatment with a PPI.5
PPIs may be indicated in the prevention of stress-related mucosal injury in the critically ill. The long-term impact of PPIs on symptoms and quality of life in patients with functional dyspepsia is debatable. Empirical use of PPIs is not indicated in patients taking corticosteroids.
Zollinger-Ellison syndrome is a rare condition characterised by severe peptic ulceration resulting from the release of gastrin by a pancreatic tumour. High doses of PPIs may be needed.