Pharmaceutical Journal Vol 263 No 7058 p241-250
August 14, 1999 Special Feature

Pharmaceutical care

(6) Gastro-oesophageal reflux disease

By Moira Kinnear, MSc, MRPharmS, Subrata Ghosh, MD, FRCP and Steve Hudson, MPharm, FRPharmS

Ms Kinnear is principal pharmacist, Western General hospital, Edinburgh, and lecturer in clinical practice, pharmaceutical care health service unit, department of pharmaceutical sciences, University of Strathclyde; Dr Ghosh is senior lecturer in medicine and consultant gastroenterologist, Western General hospital, Edinburgh; and Professor Hudson is Boots professor of pharmaceutical care, in the pharmaceutical care health service unit, University of Strathclyde, and Scottish Office national specialist in pharmaceutical care

Gastro-oesophageal reflux disease is a common problem. In some patients it is mild and self limiting but in others it can be a chronic disorder with serious consequences. This article outlines the condition and the evidence base for its treatment, before going on to discuss how pharmaceutical care can be applied to improve clinical outcome

Heartburn is a common symptom in the general population and purchased medicines are often used to relieve it.^1-3 While any patient with dyspepsia may have heartburn, the diagnosis of gastro- oesophageal reflux disease (GORD) requires symptoms of heartburn to be predominant, or for oesophagitis or acid reflux to be demonstrated (by endoscopy or oesophageal pH monitoring, respectively).
Patients with GORD therefore form a distinct rather than a non-specific category among those with dyspepsia.
GORD is the most frequent reason for the prescribing of proton pump inhibitors and is a focus for questions about cost-effective prescribing. Some clarity on the definition, diagnosis and management of the disease has been provided by a report published in April, 1999, from an international consensus meeting.⁴ The recommendations from the report contribute to efforts to improve the recognition and follow-up of patients with GORD in order to reduce the risk of complications, and they will inform the pharmaceutical care requirements of patients with GORD.
GORD may be self-limiting but can be a chronic disorder with serious consequences. The population of patients with GORD includes individuals who suffer symptoms infrequently and who treat themselves with antacids. Others may be receiving prescribed anti-reflux therapy, with or without an endoscopically confirmed diagnosis. Some patients may present at the pharmacy with acute symptoms requiring diagnosis. Only a very small minority will have a diagnosis confirmed by endoscopic investigation.

Opportunities for pharmaceutical care arise at each stage of therapy and should be documented to facilitate monitoring and continuity of care at subsequent visits to the pharmacy and to facilitate collaboration with prescribers.

Definitions

Gastro-oesophageal reflux disease (GORD) is used to describe symptoms or mucosal damage resulting from acid and pepsin. In most patients with GORD there is abnormally prolonged exposure of the oesophagus to acid and pepsin, which may result in oesophagitis of varying degrees of severity.
Complications of GORD include oesophageal stricture, oesophageal ulceration and formation of gastric columnar-lined epithelium at the gastro-oesophageal junction (Barrett’s oesophagus).
Dyspepsia is used to describe pain or discomfort centred in the upper abdomen. Heartburn, the predominant symptom in GORD, can usually be clearly distinguished from epigastric pain; other symptoms of dyspepsia are often also present in GORD.
Non-ulcer dyspepsia is a term that is no longer advocated. It has been used to describe dyspepsia associated with the absence of any endoscopic lesions.
Functional dyspepsia is the term now used to describe symptoms of dyspepsia in patients with normal endoscopic findings, after excluding those patients with "predominant" reflux symptoms.

Public health implications of GORD

Dyspepsia affects about half of the UK adult population and about half of those have symptoms of heartburn or acid regurgitation.
Half of the patients with dyspepsia are on medication and about one quarter have visited their GP regarding symptoms of dyspepsia in the past 12 months.⁷ The number of patients in the community that conform to the criteria for the diagnosis of GORD is not known.
In 1997/98, antacids and ulcer healing drugs accounted for 4.3 per cent of GP prescribing but 10.8 per cent of net GP prescribing costs in England⁸ (the equivalent figures for Scotland were 5.9 per cent and 14.5 per cent⁹).

Only 10 per cent of patients who consult their GP for dyspepsia are referred to a secondary care specialist for endoscopy. About 20 per cent of those who are endoscoped have oesophagitis.10 GORD patients also include those with predominant reflux-related symptoms in the face of normal endoscopic findings.4 Among dyspepsia patients with normal endoscopic findings, GORD is diagnosed in approximately 25 per cent and functional dyspepsia in 75 per cent.11 Some GORD patients used to be included in the general category of non-ulcer dyspepsia. The preferred term, functional dyspepsia, enables endoscopically-negative patients without predominant symptoms of heartburn to be categorised outside the definition of GORD.12 While the distinction in categorisation has complicated the study of the epidemiology of GORD, it has an important bearing on management and prognosis in terms of progression of oesophagitis and its associated complications. Treatment targeted at those with GORD should aim not only to relieve symptoms but also to heal lesions and prevent complications. Epidemiological data for dyspepsia and GORD are limited, as many individuals do not seek medical care and data on encounters with pharmacies and other sources of symptomatic remedies are not captured. The main data available have been collected from symptom surveys in randomly selected samples. Variable findings from these surveys arise from the use of different instruments and inconsistent definitions of dyspepsia and of GORD. These factors must be borne in mind when interpreting epidemiological data. Within these limitations, a profile of GORD in the community is shown in Panel 2.

Panel 2: Profile of dyspepsia in the population of a pharmacy serving 5,000 patients* 1,600 patients have suffered dyspepsia in past 12 months 800 describe dyspepsia symptoms as "just a nuisance" 800 describe dyspepsia as causing "discomfort" or worse 525 have sleep disturbed 400 have household activities affected 500 have had symptoms >5 years 800 patients report symptoms of heartburn/acid regurgitation† 65 are pregnant women with heartburn 280 have daily heartburn symptoms† 40 have severe or very severe symptoms 80 have oesophagitis 850 are taking medication 500 are taking purchased medicines 350 are taking prescribed medication for dyspepsia 225 have received a prescription for an "ulcer healing drug" in past 12 months 360 have consulted GP for dyspepsia in past 12 months in 700 consultations 180 have self-medicated prior to seeing the GP 90 have self-medicated for at least six months prior to seeing the GP 35 patients have been referred for endoscopy 7 patients have endoscopically-diagnosed GORD annually *Collated UK data 1,6,7,13,14 †Data from US 3,15

Symptom assessment in GORD

"Severe" or "very severe" symptoms are reported by approximately 5 per cent of patients with heartburn.³ Patients with frequent symptoms tend also to have more severe symptoms.³ The use of a patient questionnaire to identify and assess "reflux-like" symptoms associated with GORD might help to guide practice, although a validated clinical tool is still awaited.¹⁶ However, the value of clinical assessment is limited by the fact that neither the intensity nor the frequency of reflux-induced symptoms correlate well with the degree of oesophageal damage observed at endoscopy.¹⁴
Healing of oesophagitis and subsequent control of symptoms requires individualisation of treatment and avoidance of precipitating factors, including concomitant drug therapy. Pharmaceutical care in the uninvestigated patient relies upon accurate history taking, appropriate referral, avoidance of precipitating factors and acceptable symptom relief.

Complications of GORD

Some patients with GORD still have significant morbidity and impaired quality of life many years after initial diagnosis. For some patients, GORD is a persistent, recurring, life-long problem. The prevalence of oesophagitis in the community is estimated to be approximately 2 per cent and is found in more than half of those patients who present to their doctor with GORD.¹⁴
Chronic oesophagitis is the main cause of Barrett’s oesophagus, a condition linked to an increased risk of oesophageal stricture formation and oesophageal adenocarcinoma. Barrett’s oesophagus is reported in approximately 12 per cent of patients with symptomatic reflux.¹⁸ An important recent finding is that reflux symptoms are strongly associated with an increased risk of oesophageal adenocarcinoma (more than five-fold), independently of the presence of Barrett’s oesophagus.¹⁹ It is uncertain whether this risk can be reduced by medical or surgical means. Endoscopic surveillance in all patients with reflux symptoms cannot currently be justified in economic terms. It is currently undertaken in patients identified as having Barrett’s oesophagus.

Investigation of dyspepsia and GORD

Endoscopic investigation has a high sensitivity for diagnoses of upper gastrointestinal cancers, peptic ulcer disease and complications of oesophagitis. Barrett’s oesophagus can be confirmed from biopsies taken at endoscopy showing the typical gastric columnar epithelium. The risk of developing carcinoma of the oesophagus increases with the length of segment of Barrett’s mucosa.¹⁸
The endoscopy report usually provides management guidance for the referring doctor. Minor mucosal changes such as erythema are usually described as "endoscopy negative" so as not to misdirect management. The presence of hiatus hernia is not, on its own, diagnostic of GORD as it is not consistently associated with the condition.²⁰ Endoscopic findings may be altered if the patient has been receiving treatment with acid suppressing agents because healing may already have occurred.
If oesophagitis is observed, documented grading systems allow specific definitions of its severity. The Savary-Miller grading system (I-IV) is commonly applied, although the more recent and more objective Los Angeles grades A to D are coming into use⁴ (Table 1). In most patients with reflux symptoms there is abnormally prolonged exposure of the distal oesophagus to acid and pepsin, although in some patients with normal levels of acid/pepsin, increased oesophageal sensitivity may provide an explanation for symptoms. ²¹

Rapid symptom relief from drug therapy (omeprazole 40mg for 1-2 weeks) may have value as a diagnostic test for GORD before endoscopy or in endoscopy-negative patients.^22-25 Ambulatory pH monitoring may be necessary to diagnose endoscopy-negative patients who respond poorly to treatment. A fine pH probe is inserted transnasally to a few centimetres above the lower oesophageal sphincter. Changes in pH are recorded and stored in a data recorder worn around the patient’s waist. These pH monitors also allow patients to press a button when they experience symptoms, making it possible to relate symptoms to acid reflux. However, acid reflux is normal in some patients who continue to complain of reflux symptoms. Patients with a long history of heartburn and oesophagitis in spite of conventional treatment require investigation by a gastroenterologist.

Evidence base for the treatment of GORD

Antacids and lifestyle modifications are routinely used for first-line symptom relief although there is a lack of controlled studies on these interventions. The different H2 receptor antagonists have similar effectiveness in terms of speed of symptom relief in mild to moderate oesophagitis (grades I, II or A-B). In terms of healing and symptom relief, the proton pump inhibitors (PPIs) are more effective than H2 receptor antagonists. Table 2 provides a summary of the findings of studies in this field.

Interpretation of clinical trial data requires consideration of the fact that most studies compare the effectiveness of treatments in patients with grade II to IV oesophagitis, which represents only a minority of all patients with GORD.
Patients with GORD are not recommended for routine testing for Helicobacter pylori since most patients test negative. Also, eradication of H pylori infection does not heal or prevent relapse of reflux disease. For patients on long term proton pump inhibitors, H pylori infection has been associated with the development of atrophic gastritis, a premalignant condition for adenocarcinoma. However, eradication of H pylori prior to long-term acid suppression in GORD is controversial in the absence of proven benefit as there is some evidence that, after eradication treatment, proton pump inhibitor acid suppressing capacity is reduced, resulting in sub-optimal GORD treatment.

GORD management guidelines

The management of GORD has not been the subject of specific guidelines from a national or international body. However, a consensus from an international workshop held in Belgium in 1997 has been published recently. Table 3 and Figures 1 and 2 show an interpretation of that consensus.⁴

Patients requiring referral to the GP and endoscopy are those with alarm symptoms (listed in Panel 5) and those older than 45 years (Table 3). Patients under 45 years with severe or frequent symptoms but without alarm features also need referral to the GP but are candidates for acid suppression before further invasive investigation.

Since proton pump inhibitors are the most effective agents in GORD, a strategy using a treatment dose of PPI (usually four weeks) followed by a "step-down" in acid suppression (see hierarchy in Figure 2) has been advocated4 as an alternative to a "step-up" approach using H2 antagonists first. However, use of PPIs first-line is likely substantially to increase NHS expenditure as PPIs are costly drugs (6 per cent of prescribing costs). Until convincing evidence supports either a "step-down" or "step-up" approach in terms of cost-effectiveness, the "step-up" approach will be routinely favoured.

Figure 2: Maintenance GORD treatment - recommendations apply to all patients except those with confirmed grade C or D oesophagitis, for whom the guidance in Figure 1 applies The "step down" hierarchy is as follows: Step1, PPI double dose; step 2, PPI treatment dose; step 3, PPI half dose; step 4, H2 antagonist or cisapride; step 5, antacid

Once symptoms are controlled in non-endoscoped patients, endoscopy negative patients or those with mild oesophagitis, an initial trial of immediate discontinuation of acid suppression therapy is advised. If symptoms recur, a "step down" of acid suppression (at four to eight week intervals) may be used to establish the minimum treatment required to prevent further relapse. An alternative strategy after immediate discontinuation of acid suppressant is to treat relapse either with a fixed course (two to four weeks) of PPI or H2 antagonist⁵⁸ or with "on demand" PPI until symptom resolution.^59,60

In patients with severe oesophagitis (endoscopic grades C and D), PPI therapy at treatment dose is recommended to heal the disease.4 If symptoms persist, the dose should be doubled for eight weeks. Repeat endoscopy is necessary in all patients with severe oesophagitis, either to confirm healing after symptom control or to reassess persistent symptoms (Figure 1). Step-down treatment is not recommended in this group as patients are likely to relapse unless maintained on PPI therapy.4 The safety of long-term use of PPIs has recently been reviewed, with the conclusion that the drugs have a wide safety margin.61

Figure 1: GORD management (following initial symptom assessment, as in Table 3)

Individualised care

More than 50 per cent of patients with GORD have mild symptoms and function well without feeling the need to visit the GP. Some 20-40 per cent of patients consult their GP and receive prescribed medication. Fewer than 10 per cent are known to have complications of oesophagitis. Many patients self-medicate for at least six months before seeking professional advice.^1,7,62 Patients seeking medical attention tend to be older with more severe heartburn; this group includes some patients with health-seeking behaviour characteristics, including fears of malignancy.^63,64
Patients who use antacids regularly are thought to suffer from GORD.⁶² Patients on regular antacid and those who purchase H2 antagonists and domperidone therefore require to be assessed for review of their self-management and possible medical referral. In particular, elderly patients are at risk of inappropriate use of these medicines.
Endoscopic follow up after initial treatment of patients with mild oesophagitis has shown that about half heal and have no further episodes of oesophagitis, while about one quarter progress to a more severe form.⁶⁵ A patient’s needs may therefore change. In the absence of adequate maintenance therapy, oesophagitis relapses in 50 to 90 per cent of patients within six to 12 months. Most patients relapse to their pre-treatment grade of disease.⁶⁵
The pharmaceutical care needs of patients with GORD in primary care are difficult to characterise since the majority of sufferers do not have their diagnosis confirmed. This is because many sufferers rely on self-medication and in those who do consult their doctor there is overlap of symptoms with functional dyspepsia and peptic ulcer disease. Guideline development in dyspepsia has focused on appropriate use of resources with regard to endoscopic investigation and H pylori eradication in peptic ulcer disease. Guidelines to help structure pharmaceutical care for GORD are now emerging.

Table 4 suggests pharmaceutical care issues that need to be addressed in this patient group.

Careful monitoring of symptoms is required at all stages in the management of GORD to ensure identification of patients at risk of complications and to optimise therapeutic management. In each patient, the level of acid suppression necessary to maximise the benefits of symptom control and the patient’s quality of life needs to be continuously monitored, periodically reviewed and treatment perhaps stepped down or discontinued after a period of healing or control of symptoms. Patients themselves require a clear understanding of the nature of their condition to enable them to take an active role in the achievement of these shared goals.

Therapeutic plans which include a "stepped" approach to care should be explained clearly to patients and this may motivate them to participate in monitoring response to therapy and subsequent therapeutic adjustment. Many patients receive repeat prescriptions for acid suppressing agents. Pharmacists can contribute to patient monitoring and review of therapy, patient referral and therapy adjustment.
Pharmacists have identified upper GI disease as a point of collaboration with GPs in primary care. The development of pharmacy services within GP practices and a focus on acid suppressing drug use provides opportunities to develop systems to support continuity of pharmaceutical care. Although there is currently a lack of published information on pharmaceutical care delivery in GORD, pharmacists employed within a GP practice can verify the diagnostic category for patients investigated from endoscopy records and can develop and implement clinical guidelines. Patients who are to be referred for investigation can be counselled to ensure prior discontinuation of PPI to avoid any PPI interference with the interpretation of endoscopic findings. (Advice is to stop the PPI at least two weeks before endoscopy.)
Documentation of episodes of care will help to clarify these data and provide opportunities to communicate history of purchased medicine use to GPs, who might not otherwise be able to give full regard to this aspect of care. Pharmacists can contribute to screening and appropriate referral of individuals through identification of progression of symptoms and possible adverse drug reactions. Treatment success should be assessed, patient education re-inforced and antacid therapy reviewed at subsequent patient visits to the pharmacy.

Conclusion

GORD is a common health care problem for which there is opportunity to improve clinical outcomes (symptom control, healing) by identifying patients at special risk of complications or those with poor control. By achieving good quality contact with patients, pharmacists can prepare drug histories and refer appropriate patients who require investigation.
Pharmaceutical care can contribute to the implementation of local guidelines in GORD and, consequently, to improved patient outcomes and improved use of medicine resources.

Cases

References