DYSPEPSIA MANAGEMENT by jaider maya

Review Article Dig Dis 2008;26:225–230 DOI: 10.1159/000121351

Current Guidelines for Dyspepsia Management Alexander C. Ford a Paul Moayyedi b a b

Department of Academic Medicine, St. James’s University Hospital, Leeds, UK; Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ont., Canada

Key Words Dyspepsia ⴢ Helicobacter pylori ⴢ Endoscopy ⴢ Management guidelines

Abstract Background: Dyspepsia is a global problem and the management of the condition remains a considerable burden on health care resources. Many countries have adopted evidence-based guidelines for the management of the condition, in an attempt to reduce health care expenditure. This article compares and contrasts dyspepsia management guidelines from several geographical regions. Methods: We obtained current guidelines from five regions and examined composition of guideline development groups, methodology involved, definition of dyspepsia utilized, and recommendations in terms of first-line approach, age cutoff for prompt upper gastrointestinal (GI) endoscopy, and subsequent role of endoscopy. Results: All guidelines carried out extensive reviews of the literature to inform their recommendations. The majority used a definition of dyspepsia in line with the Rome criteria. All agreed that alarm symptoms at any age warranted prompt endoscopy, and most recommended an age cutoff of between 50 and 55 years for endoscopy as an initial management strategy. In young patients without alarm symptoms, either ‘test and treat’ or empirical acid suppression were the initial management strategies of choice in all cases, with only one guideline recommending

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mandatory endoscopy in those whose symptoms failed to settle after this approach. Conclusions: Despite varying composition of guideline development groups and the different geographical regions, the recommendation of all the guidelines were remarkably similar, reflecting the quality of research conducted by the GI community as a whole. Copyright © 2008 S. Karger AG, Basel

Introduction

Dyspepsia is a complex of symptoms referable to the upper gastrointestinal (GI) tract. Surveys have shown that dyspepsia is a global problem with 15–40% of populations from Asia to North America complaining of upper GI symptoms [1–7]. The variation in prevalence estimates depends more on the definition of dyspepsia used than the country studied [8, 9]. The prevalence of dyspepsia remains relatively stable, even during prolonged periods of follow-up, as the resolution of symptoms in some individuals is matched by the spontaneous development of symptoms in others [7, 10, 11]. The presence of symptoms of dyspepsia may lead an individual to consult a physician. This probably occurs as a result of a combination of fear of serious illness, patient demographics, or the frequency or severity of the symptoms themselves [2, 3, 12–14]. It is estimated that between 25 and 40% of individuals with dyspepsia will consult a Dr. Alex Ford Department of Academic Medicine, Clinical Sciences Building St. James’s University Hospital, Room 7.23 Leeds LS9 7TF (UK) Tel. +44 113 269 7975, Fax +44 113 242 9722, E-Mail alexf12399@yahoo.com

primary care physician as a result of their symptoms [2, 3, 12]. This presents the clinician with a problem, as the underlying pathology may vary from the life-threatening to the benign. The four major etiologies include gastric and esophageal malignancy, peptic ulcer disease, gastroesophageal reflux disease (GERD), and functional dyspepsia, the latter occurring when epigastric-predominant symptoms are present in the absence of a definite structural cause at upper GI endoscopy. In studies that have reported findings at upper GI endoscopy in those with dyspepsia, 40 to 60% of individuals have a normal examination, whilst gastro-esophageal malignancy is typically present in less than 1% in Western populations [15–17]. The approach to these statistics will depend upon how risk averse both the patient and the clinician are to uncertainty. There are four widely accepted management strategies, and all have been compared in randomized controlled trials (RCTs) [18–27]. Those that wish to eliminate all possible risk in managing dyspepsia advocate prompt upper GI endoscopy for all patients presenting with symptoms, in an attempt to exclude gastro-esophageal malignancy which, if present, may be detected at a stage where it is more amenable to surgical cure. Since dyspepsia is such a prevalent condition in the general population, and a large proportion of patients will have normal endoscopic findings, it is not feasible to recommend prompt endoscopy for all individuals who consult with dyspepsia. There are two practical reasons for this. Firstly, endoscopy remains a relatively expensive investigative procedure [28]. Secondly, upper GI endoscopy is invasive, and carries the risk of potential complications that, although rare, may have grave consequences. Indeed, in younger patients, in whom serious disease is less likely, these complications may exceed the perceived benefits. Attempts have therefore been made in the West to rationalize the use of endoscopy by restricting its use to those above a certain age, as younger patients have a much lower incidence of upper GI malignancy [29–34], or to those who present with ‘alarm’ symptoms, which are thought to be predictive of underlying malignant disease, though in reality the positive predictive value of such symptoms is poor [31, 35, 36]. Testing for Helicobacter pylori and endoscopy for only those who test positive (a so-called ‘test and scope’ approach) has been proposed as an alternative, in an attempt to reduce endoscopy workload. Testing for H. pylori followed by treatment with eradication therapy for positive individuals (‘test and treat’) is another option, and the efficacy of this approach is thought to arise from a combination of successful treatment of latent peptic ul226

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cer disease [37], as well as a modest effect on the symptoms of functional dyspepsia [38]. The final strategy is one of empirical acid suppression therapy with either a proton pump inhibitor (PPI) or an H2-receptor antagonist (H2RA). As dyspepsia is prevalent worldwide, many developed countries have adopted guidelines for the management of dyspepsia, primarily in an attempt to use an evidencebased approach to the management of the condition in order to reduce dyspepsia-related health care expenditure. These serve as a useful way of summarizing the current available evidence and distilling it in such a way that clinical practice becomes standardized. The remainder of this article compares and contrasts dyspepsia management guidelines from various countries or regions.

Dyspepsia Guidelines

The guidelines reviewed in this article have been produced by the Canadian Dyspepsia (CanDys) Working Group [39], the England and Wales National Institute of Clinical Excellence (NICE) [40], the Scottish Intercollegiate Guidelines Network (SIGN) [41], the American College of Gastroenterology (ACG) [42], the American Gastroenterological Association (AGA) [43], and the AsiaPacific Working Party [44]. Composition of the Guideline Development Groups The NICE guidelines and CanDys Working Group were developed from a primary care perspective. The NICE group consisted predominantly of primary care physicians but with gastroenterology and pharmacy input, whilst the CanDys group consisted of a more equal mix of gastroenterologists and primary care physicians. The SIGN guidelines were developed from a general health service perspective and the development panel consisted of gastroenterologists, primary care physicians, general surgeons, radiologists, pharmacists and dieticians. The SIGN and NICE guidelines were the only guidelines to include specific methodology experts and patient representatives. The remaining guidelines were all developed from a gastroenterology perspective and the group mainly consisted of gastroenterologists. The ACG and AGA guidelines were written by two or three gastroenterologists in conjunction with the ACG Practice Parameters Committee and the AGA Clinical Practice and Economics Committee respectively. Two out of the three authors of the ACG and AGA guidelines were the same and the guidelines were written within 12 months Ford /Moayyedi

Table 1. Summary of guidelines for dyspepsia

Guideline

Dyspepsia definition

When to endoscope

Place of H. pylori test and treat

Use of PPI therapy

ACG 2005 (US)

Rome II

Age >55 or alarm features (any age) If H. pylori eradication and/or PPI fails in those ≤55 consider

H. pylori test and treat if prevalence >10%, empirical PPI in lower prevalence areas

Empiric PPI therapy first line in low H. pylori prevalence areas After H. pylori test if negative or positive and failing treatment in high prevalence areas Standard doses of PPI therapy should be used with double doses considered if symptoms persist

AGA 2005 (US)

Rome II

Age >55 or alarm features (any age) If H. pylori eradication and/or PPI fails in those ≤55 consider

H. pylori test and treat if prevalence >10%, empirical PPI if prevalence <5%, if 5–10% strategy uncertain

Empiric PPI therapy first line in low H. pylori prevalence areas After H. pylori test if negative or positive and failing treatment in high prevalence areas

NICE 2004 (England and Wales)

All upper GI symptoms

Age >55 or alarm features (any age) If H. pylori eradication and/or PPI fails in those ≤55 consider

Evidence of H. pylori test and treat or empiric PPI therapy uncertain so first line choice left to individual preference If one fails try the other

Initial therapy should be standard dose for one month Then patient should be managed with on-demand PPI therapy at the lowest dose that manage the patient’s symptoms

SIGN 2003 (Scotland)

Rome II

Alarm features (any age) Consider referral to secondary care if ≥55 years and symptoms persist

First line for those with dyspepsia and no alarm symptom at any age

Empiric PPI therapy if H. pylori eradication fails Dose not explicitly stated

CanDys 2005 (Canada)

All upper GI symptoms, except isolated heartburn

Age >50 or alarm features (any age) If H. pylori eradication and/or PPI fails in those ≤50 consider

H. pylori test and treat if epigastric pain is the dominant problem

Empiric acid suppression if heartburn is the predominant problem Standard dose PPI for 4–8 weeks then consider on demand PPI or stepping down to H2RA

AsiaPacific working party 1998

Rome I

Age 35–55 (depending on risk of gastric cancer in the region) or alarm features (any age)

Consider H. pylori test and treat if patient fails empiric acid suppression and/or prokinetic therapy In areas with high prevalence of H. pylori this strategy unlikely to be beneficial

First-line therapy for young patients with no alarm features Either PPI or H2RA at standard dose

of each other, so these guidelines would be expected to show the greatest similarity. Guideline Development Methodology All the guidelines reviewed in this article were informed by extensive reviews of the literature to obtain contemporaneous available scientific evidence. In most cases this evidence was graded according to quality. Where evidence was lacking expert consensus, either from the literature or from the guideline development groups, was used in some cases. In the case of the NICE guidelines, several systematic reviews and meta-analyses Current Guidelines for Dyspepsia Management

of RCTs were also undertaken as part of the development process. The AGA guidelines used these systematic reviews, as well as conducting others on the utility of alarm symptoms in diagnosing upper GI malignancy. In the NICE, SIGN, CanDys Working Group and the Asia-Pacific Working Party guidelines consensus was reached by the jury method which is an informal approach used for a group to reach consensus. The AGA and ACG guidelines were written by two to three authors who informally reached agreement amongst themselves, and this was modified by committees appointed by the relevant society. None of the guidelines used formal consensus methDig Dis 2008;26:225–230

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ods such as the modified Delphi or nominal group techniques. Recommendations of the Guidelines Despite the varying make-up of the development groups and the methodology used, as well as differences in the target audiences, the guidelines provide remarkably similar management strategies for dyspepsia. This is probably because the underlying evidence base in this field is so good, and this reflects well on the GI community as a whole. There are some differences, however, and these are discussed below and detailed in table 1. Differences in the Definition of Dyspepsia Used by the Guidelines The majority of the guidelines used a definition of dyspepsia that is in line with the Rome criteria, where those with suspected GERD are excluded. The exceptions to this are the NICE guidelines and the CanDys clinical management tool. The former used a broad definition of dyspepsia that included all symptoms referable to the upper GI tract, whilst the latter only excluded those with isolated heartburn. This probably reflects the fact both were developed with a primary care audience in mind, where physicians are often consulting with patients before the results of investigations are available, and even when these are on hand, studies suggest that the value of distinctions made on the grounds of symptom patterns alone are imperfect, due to poor sensitivity and specificity of individual symptoms for predicting underlying pathology, as well as considerable overlap of both individual symptoms and symptom subgroups [16, 45, 46]. Differences in the Age Cutoff for Prompt Endoscopy In terms of when to offer prompt endoscopy, all the guidelines are in agreement that individuals of any age with alarm symptoms warrant this, though it is accepted that the predictive value of these symptoms is poor, and the yield of endoscopy in this setting is low [15, 17]. The age cutoff recommended by the various guidelines for when to offer prompt endoscopy in uncomplicated dyspepsia varies from 50 to 55 years of age, the age at which incidence of upper GI malignancy is said to significantly increase, with the exception of the Asia-Pacific Working Party and the SIGN guidelines. The former did not set a specific cutoff, as a number of countries were represented with varying risks of upper GI malignancy and different health care budgets, though they suggested an age from 35 years in very-high-risk developed countries such as Japan and made no recommendation for endoscopy at all 228

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in low-risk developing countries. The SIGN guidelines do not recommend prompt endoscopy as the management of choice at any upper age limit, because it is felt that there is no evidence that potentially curable gastric cancer found at endoscopy for uncomplicated dyspepsia is anything other than a chance finding. Some of these differences may have arisen due to differences in the way health service provision is funded between the UK and the US. The publicly funded UK system may be expected to recommend a reduction in the use of endoscopy, if this is unlikely to adversely affect patient care, in order to minimize costs. Differences in First-Line Approach to Young Patients with Uncomplicated Dyspepsia SIGN and the CanDys clinical management tool recommend a first-line strategy of ‘test and treat’ with eradication therapy for positives and a trial of empirical acid suppression for negative individuals. Both the ACG and AGA state that if the prevalence of H. pylori in the local population is ten percent or more, then ‘test and treat’ with empirical acid suppression for negatives should be first-line management, with empirical acid suppression as first-line in areas of lower prevalence. NICE state that there is no current available evidence as to which of these two strategies is superior, and therefore either should be offered. Differences in When to Offer Endoscopy Subsequently In young patients with uncomplicated dyspepsia, either H. pylori ‘test and treat’ with PPI for those testing negative, or empirical acid suppression therapy are recommended as first-line management strategies by all the guidelines, depending on the prevalence of H. pylori in the local population. For those whose symptoms persist or recur following either, or both, of these approaches, only the CanDys clinical management tool advocates endoscopy to confirm or refute the presence of underlying pathology. The ACG and AGA guidelines state that some patients, particularly those who are anxious, may require the reassurance afforded by endoscopy, but that it should not be routinely offered. The NICE guidelines state that endoscopy should be considered only if medical therapy has failed. Finally, the SIGN guidelines do not recommend endoscopy at all in this setting, but state that for those aged 55 years and over, referral to a specialist in secondary care should be considered.

Ford /Moayyedi

Conclusions

Dyspepsia is a common complaint, and the management of the condition represents a considerable financial burden for the health service. The development of guidelines standardizes treatment and reduces costs, whilst maintaining patient safety. Despite the excellent evidence base already in existence that has been used to inform much of the recommendations contained in the various guidelines, gaps in current knowledge still exist. We still do not know the lower limit of H. pylori prevalence at

which a ‘test and treat’ strategy remains cost-effective. Nor do we have any clear evidence for the use of an upper age limit for referral for prompt endoscopy, and if so, at what age that should be set. Finally, though we now have strong evidence that ‘test and treat’ is a more cost-effective management strategy than prompt endoscopy for the initial management of uncomplicated dyspepsia [47], it is still not clear whether it is more cost-effective than empirical acid suppression therapy, though one large trial in the UK has recently been completed that may answer this question [48].

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