The National Institute for Clinical Excellence issued guidance on use of proton pump inhibitors (PPIs) in dyspepsia on July 11. It recommends that all doctors review their use of PPIs "with the aim of reducing the dose or even stopping the medicine, where appropriate."
The NICE says that implementation of its guidance could lead to a reduction in usage of PPIs of at least 15 per cent, giving an annual saving to the NHS in England and Wales of £40m to £50m in drug costs.
The guidance covers use of PPIs in the various different types of dyspepsia.
In documented peptic ulceration, a strategy of testing for H pylori and, where positive, eradicating the infection, is recommended. Long-term acid suppression should not be used, the guidelines say. PPIs can be used for patients who are H pylori negative or who remain symptomatic after eradication therapy.
The NICE says that an acid suppressor, usually a PPI, should be prescribed for those patients with NSAID-induced ulcer who must continue with NSAID therapy. After the ulcer has healed, the patient should, where possible, be stepped down to a maintenance dose, it adds.
Patients who have severe gastro-oesophageal reflux disorder (GORD) symptoms or who have a proven pathology (eg, oesophageal ulceration, Barrett's oeophagus) should be treated with a healing dose of a PPI until symptoms have been controlled. After that, the dose should be "stepped down." "A regular maintenance low dose of most PPIs will prevent recurrent GORD symptoms in 70 to 80 per cent of patients and should be used in preference to the higher healing dose," the guidance says. Where necessary, should symptoms reappear, the higher dose should be restarted. In complicated oesophagitis (stricture, ulcer, haemorrhage), the full dose should be maintained.
Patients with mild GORD symptoms can frequently be managed by other therapies, eg, antacids, alginates or H2 antagonists, at least in the first instance, says the NICE, adding that, while PPIs are the most effective drug for mild GORD, they may not be the most cost-effective.
Patients diagnosed with non-ulcer dyspepsia should not be routinely treated with PPIs. "The available evidence shows that PPIs are marginally, if at all, more beneficial than placebo in the treatment of non-ulcer dyspepsia."
The NICE says that patients presenting to the GP with mild symptoms of dyspepsia may be treated on either a "step up" or a "step down" basis. It adds that neither group should normally be treated with PPIs on a long-term basis without a confirmed clinical diagnosis being made.
The NICE urges use of the "least expensive appropriate PPI." And, on dosing, it says: "In circumstances where it is appropriate to use a PPI and where healing is required, the optimal dose to achieve this should be prescribed initially. Once healing has been achieved, or for conditions where it is not required, the lowest dose of the PPI that provides effective symptom relief should be used."
In England and Wales in 1998, the NHS spent £314m on PPIs. On the cost implications of its guidance, the NICE says that the full savings in drug costs are likely to be offset by increased costs of diagnostic testing and by monitoring of those patients who have to take PPIs over a long period.
Discussing how a 15 per cent reduction in PPI use could be achieved, a NICE spokeswoman said on July 11 that savings could arise in two ways: from avoiding use in conditions where a PPI was not warranted in the first instance (eg, mild GORD and H pylori-positive patients with ulceration) and from "stepping down" of treatment when appropriate. She said that some patients were kept on repeat prescriptions for PPIs at too high a dose and for too long.
Asked to comment on the guidelines, Ms Moira Kinnear (principal pharmacist [gastrointestinal medicine], Western General hospital, Edinburgh) said that she was sure that pharmacists would welcome the guidelines, but she felt that the section on GORD had potential for confusion. The management strategy for complicated oesophagitis appropriately recommended full-dose maintenance therapy. However, the strategy for patients with proven pathology such as oesophageal ulceration and Barrett's oesophagus recommended a step-down approach to care. "Many practitioners might consider oesophageal ulceration and Barrett's oesophagus as complicated disease, hence confusion may arise in which strategy to follow." Ms Kinnear said that she thought that one of the most important factors in terms of the cost-effective use of PPIs was regular monitoring of patients, with appropriate adjustments to therapy.
Wyeth Laboratories (manufacturer of lansoprazole) and BASF Pharma (manufacturer of pantoprazole) appealed against the proposed NICE guidance but their appeals were dismissed at a hearing on June 29.
One of Wyeth's complaints was that the guidance was "perverse" as trial data submitted clearly showed, in its opinion, that one PPI was superior to another in terms of clinical efficacy. The company felt that the statement that "the least expensive appropriate PPI should be used" was not logical or reasonable. The appeal panel dismissed this point on the ground that NICE was not charged with carrying out a review of one PPI against another.
Responding to the publication of the guidance on July 11, Wyeth said that it welcomed the NICE endorsement of the important role of the PPIs but had some concerns about the review process. "We would ask that the process and criteria by which NICE evaluates products and therapies become more open and transparent."
Astra Zeneca (manufacturer of omeprazole) also said that it had concerns about NICE and its processes.
The full guidelines are available on the NICE website (www.nice.org.uk).